PMID- 25923550 OWN - NLM STAT- MEDLINE DA - 20150430 DCOM- 20150518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 372 IP - 18 DP - 2015 Apr 30 TI - Rociletinib in EGFR-mutated non-small-cell lung cancer. PG - 1700-9 LID - 10.1056/NEJMoa1413654 [doi] AB - BACKGROUND: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M. METHODS: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles. RESULTS: A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51). CONCLUSIONS: Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; ClinicalTrials.gov number, NCT01526928.). FAU - Sequist, Lecia V AU - Sequist LV AD - From Massachusetts General Hospital (L.V.S., R.S.H., J.L., Z.P.), Harvard Medical School (L.V.S., G.R.O., R.S.H., Z.P.), and Dana-Farber Cancer Institute (G.R.O.) - all in Boston; the Drug Development Department, Universite Paris-Sud, Gustave Roussy Cancer Campus (J.-C.S.), and Institut Gustave Roussy (A.V.), Villejuif - both in France; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.W.G., E.B.G., M.A.M., S.N.), and Stanford Cancer Institute, Stanford University, Stanford (H.A.W., J.W.N.) - both in California; the Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit (S.M.G., C.G., A.J.W.); University of Texas M.D. Anderson Cancer Center, Houston (V.P.); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.); the Medical University of Gdansk, Gdansk, Poland (R.D.); the University of Colorado (D.L.A., D.R.C.) and University of Colorado Cancer Center (R.C.D.) - both in Aurora; and Clovis Oncology, San Francisco (M.R., C.A.K., S.J.-T., S.L.M., A.R.A.), Boulder, CO (J.I., D.D.), and Cambridge, United Kingdom (L.R.). FAU - Soria, Jean-Charles AU - Soria JC FAU - Goldman, Jonathan W AU - Goldman JW FAU - Wakelee, Heather A AU - Wakelee HA FAU - Gadgeel, Shirish M AU - Gadgeel SM FAU - Varga, Andrea AU - Varga A FAU - Papadimitrakopoulou, Vassiliki AU - Papadimitrakopoulou V FAU - Solomon, Benjamin J AU - Solomon BJ FAU - Oxnard, Geoffrey R AU - Oxnard GR FAU - Dziadziuszko, Rafal AU - Dziadziuszko R FAU - Aisner, Dara L AU - Aisner DL FAU - Doebele, Robert C AU - Doebele RC FAU - Galasso, Cathy AU - Galasso C FAU - Garon, Edward B AU - Garon EB FAU - Heist, Rebecca S AU - Heist RS FAU - Logan, Jennifer AU - Logan J FAU - Neal, Joel W AU - Neal JW FAU - Mendenhall, Melody A AU - Mendenhall MA FAU - Nichols, Suzanne AU - Nichols S FAU - Piotrowska, Zofia AU - Piotrowska Z FAU - Wozniak, Antoinette J AU - Wozniak AJ FAU - Raponi, Mitch AU - Raponi M FAU - Karlovich, Chris A AU - Karlovich CA FAU - Jaw-Tsai, Sarah AU - Jaw-Tsai S FAU - Isaacson, Jeffrey AU - Isaacson J FAU - Despain, Darrin AU - Despain D FAU - Matheny, Shannon L AU - Matheny SL FAU - Rolfe, Lindsey AU - Rolfe L FAU - Allen, Andrew R AU - Allen AR FAU - Camidge, D Ross AU - Camidge DR LA - eng SI - ClinicalTrials.gov/NCT01526928 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Acrylamides) RN - 0 (Antineoplastic Agents) RN - 0 (CO-1686) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - AIM SB - IM CIN - N Engl J Med. 2015 Apr 30;372(18):1760-1. PMID: 25923556 MH - Acrylamides/*administration & dosage/adverse effects/pharmacokinetics MH - Aged MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Dose-Response Relationship, Drug MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - Humans MH - Hyperglycemia/chemically induced MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects/pharmacokinetics MH - Pyrimidines/*administration & dosage/adverse effects/pharmacokinetics MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics EDAT- 2015/04/30 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/04/30 06:00 AID - 10.1056/NEJMoa1413654 [doi] PST - ppublish SO - N Engl J Med. 2015 Apr 30;372(18):1700-9. doi: 10.1056/NEJMoa1413654. PMID- 25923549 OWN - NLM STAT- MEDLINE DA - 20150430 DCOM- 20150518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 372 IP - 18 DP - 2015 Apr 30 TI - AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. PG - 1689-99 LID - 10.1056/NEJMoa1411817 [doi] AB - BACKGROUND: The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. METHODS: We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy. RESULTS: A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients. CONCLUSIONS: AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01802632.). FAU - Janne, Pasi A AU - Janne PA AD - From the Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston (P.A.J.); National Taiwan University and National Taiwan University Hospital (J.C.-H.Y.) and Cheng Kung University Hospital (W.-C.S.) - both in Taipei, Taiwan; Seoul National University Hospital (D.-W.K.), Samsung Medical Center (M.-J.A.), Asan Medical Center (S.-W.K.), and Yonsei Cancer Center, Yonsei University Health System (J.-H.K.) - all in Seoul, South Korea; Institut Gustave Roussy, Villejuif, France (D.P.); National Cancer Center Hospital, Tokyo (Y.O.); Winship Cancer Institute of Emory University, Atlanta (S.S.R.); Vanderbilt Ingram Cancer Center, Nashville (L.H.); Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC (D.H.); Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona (E.F.); and AstraZeneca, Macclesfield (P.F., M.C., K.H.B., P.A.D., S.G.), and University of Manchester, Christie Hospital, Manchester (M.R.) - both in the United Kingdom. FAU - Yang, James Chih-Hsin AU - Yang JC FAU - Kim, Dong-Wan AU - Kim DW FAU - Planchard, David AU - Planchard D FAU - Ohe, Yuichiro AU - Ohe Y FAU - Ramalingam, Suresh S AU - Ramalingam SS FAU - Ahn, Myung-Ju AU - Ahn MJ FAU - Kim, Sang-We AU - Kim SW FAU - Su, Wu-Chou AU - Su WC FAU - Horn, Leora AU - Horn L FAU - Haggstrom, Daniel AU - Haggstrom D FAU - Felip, Enriqueta AU - Felip E FAU - Kim, Joo-Hang AU - Kim JH FAU - Frewer, Paul AU - Frewer P FAU - Cantarini, Mireille AU - Cantarini M FAU - Brown, Kathryn H AU - Brown KH FAU - Dickinson, Paul A AU - Dickinson PA FAU - Ghiorghiu, Serban AU - Ghiorghiu S FAU - Ranson, Malcolm AU - Ranson M LA - eng SI - ClinicalTrials.gov/NCT01802632 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (AZD9291) RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - AIM SB - IM CIN - N Engl J Med. 2015 Apr 30;372(18):1760-1. PMID: 25923556 MH - Acrylamides/*administration & dosage/adverse effects/pharmacokinetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds/*administration & dosage/adverse effects/pharmacokinetics MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics MH - Disease-Free Survival MH - Dose-Response Relationship, Drug MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/genetics MH - Male MH - Middle Aged MH - Mutation MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects/pharmacokinetics MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics EDAT- 2015/04/30 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/04/30 06:00 AID - 10.1056/NEJMoa1411817 [doi] PST - ppublish SO - N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817. PMID- 25806711 OWN - NLM STAT- MEDLINE DA - 20150326 DCOM- 20150519 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 38 IP - 2 DP - 2015 Apr TI - MYC and human telomerase gene (TERC) copy number gain in early-stage non-small cell lung cancer. PG - 152-8 LID - 10.1097/COC.0000000000000012 [doi] AB - OBJECTIVES: We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non-small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. MATERIALS AND METHODS: Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. RESULTS: When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean >/= 2.83 copies/cell) and TERC (mean >/= 2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P=0.02) and the ROC classification (P=0.008). CONCLUSIONS: Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. FAU - Flacco, Antonella AU - Flacco A AD - *Department of Medical Oncology, S. Maria della Misericordia Hospital Departments of daggerElectronic and Information Engineering double daggerThoracic Surgery section signInstitute of Pathological Anatomy and Histology, University of Perugia, Perugia, Italy parallelDepartment of Medicine/Medical Oncology, University of Colorado Cancer Center, Aurora, CO. FAU - Ludovini, Vienna AU - Ludovini V FAU - Bianconi, Fortunato AU - Bianconi F FAU - Ragusa, Mark AU - Ragusa M FAU - Bellezza, Guido AU - Bellezza G FAU - Tofanetti, Francesca R AU - Tofanetti FR FAU - Pistola, Lorenza AU - Pistola L FAU - Siggillino, Annamaria AU - Siggillino A FAU - Vannucci, Jacopo AU - Vannucci J FAU - Cagini, Lucio AU - Cagini L FAU - Sidoni, Angelo AU - Sidoni A FAU - Puma, Francesco AU - Puma F FAU - Varella-Garcia, Marileila AU - Varella-Garcia M FAU - Crino, Lucio AU - Crino L LA - eng GR - P30 CA046934/CA/NCI NIH HHS/United States GR - P50 CA58187/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 RN - 0 (telomerase RNA) RN - 63231-63-0 (RNA) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Area Under Curve MH - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology MH - Disease-Free Survival MH - Female MH - *Gene Dosage MH - Genes, myc/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*genetics/mortality/pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Proportional Hazards Models MH - RNA/*genetics MH - ROC Curve MH - Retrospective Studies MH - Telomerase/*genetics EDAT- 2015/03/26 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/03/26 06:00 AID - 10.1097/COC.0000000000000012 [doi] AID - 00000421-201504000-00006 [pii] PST - ppublish SO - Am J Clin Oncol. 2015 Apr;38(2):152-8. doi: 10.1097/COC.0000000000000012. PMID- 25803563 OWN - NLM STAT- MEDLINE DA - 20150325 DCOM- 20150519 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 38 IP - 2 DP - 2015 Apr TI - ACR Appropriateness Criteria((R)) induction and adjuvant therapy for N2 non-small-cell lung cancer. PG - 197-205 LID - 10.1097/COC.0000000000000154 [doi] AB - The integration of chemotherapy, radiation therapy (RT), and surgery in the management of patients with stage IIIA (N2) non-small-cell lung carcinoma is challenging. The American College of Radiology (ACR) Appropriateness Criteria Lung Cancer Panel was charged to update management recommendations for this clinical scenario. The Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. There is limited level I evidence to guide patient selection for induction, postoperative RT (PORT), or definitive RT. Literature interpretation is complicated by inconsistent diagnostic procedures for N2 disease, disease heterogeneity, and pooled analysis with other stages. PORT is an appropriate therapy following adjuvant chemotherapy in patients with incidental pN2 disease. In patients with clinical N2 disease who are potential candidates for a lobectomy, both definitive and induction concurrent chemotherapy/RT are appropriate treatments. In N2 patients who require a pneumonectomy, definitive concurrent chemotherapy/RT is most appropriate although induction concurrent chemotherapy/RT may be considered in expert hands. Induction chemotherapy followed by surgery +/- PORT may also be an option in N2 patients. For preoperative RT and PORT, 3-dimensional conformal techniques and intensity-modulated RT are most appropriate. FAU - Willers, Henning AU - Willers H AD - *Massachusetts General Hospital, Boston, MA daggerUniversity of North Carolina Health Care System, American Society of Clinical Oncology, Chapel Hill, NC double daggerIndiana University School of Medicine, Indianapolis, IN section signHenry Ford Health System #Henry Ford Hospital, Detroit, MI paragraph sign21st Century Oncology/Michigan Healthcare Professionals, Farmington Hills, MI parallelSociety of Thoracic Surgeons, Columbia University, New York, NY daggerdaggerMemorial Sloan Kettering Cancer Center, New York, NY double daggerdouble daggerMount Sinai School of Medicine, New York, NY **Stanford University and Stanford Cancer Institute, Stanford, CA section sign section signCleveland Clinic Foundation, Cleveland, OH parallel parallelUniversity of Texas MD Anderson Cancer Center, Houston, TX. FAU - Stinchcombe, Thomas E AU - Stinchcombe TE FAU - Barriger, R Bryan AU - Barriger RB FAU - Chetty, Indrin J AU - Chetty IJ FAU - Ginsburg, Mark E AU - Ginsburg ME FAU - Kestin, Larry L AU - Kestin LL FAU - Kumar, Sanath AU - Kumar S FAU - Loo, Billy W Jr AU - Loo BW Jr FAU - Movsas, Benjamin AU - Movsas B FAU - Rimner, Andreas AU - Rimner A FAU - Rosenzweig, Kenneth E AU - Rosenzweig KE FAU - Videtic, Gregory M M AU - Videtic GM FAU - Chang, Joe Yujiao AU - Chang JY CN - Expert Panel on Radiation Oncology-Lung: LA - eng PT - Journal Article PT - Practice Guideline PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 RN - 0 (Antineoplastic Agents) SB - IM MH - Antineoplastic Agents/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*therapy MH - Chemotherapy, Adjuvant/*methods MH - Combined Modality Therapy/methods MH - Humans MH - Lung Neoplasms/*therapy MH - Pneumonectomy/*methods MH - Radiotherapy, Adjuvant/*methods EDAT- 2015/03/25 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/03/25 06:00 AID - 10.1097/COC.0000000000000154 [doi] AID - 00000421-201504000-00013 [pii] PST - ppublish SO - Am J Clin Oncol. 2015 Apr;38(2):197-205. doi: 10.1097/COC.0000000000000154. PMID- 25778312 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150430 IS - 1107-0625 (Print) IS - 1107-0625 (Linking) VI - 20 IP - 1 DP - 2015 Jan-Feb TI - Correlation of tumor size as independent factor and disease stage with local recurrence of non-small cell lung carcinoma and its operability. PG - 166-72 AB - PURPOSE: To analyze the correlation of non-small cell lung carcinoma (NSCLC) primary tumor size, independently, and the initial disease stage with the incidence of local recurrence (LR) and disease-free survival (DFS), as well as the LR operability. METHODS: The research was conducted on 114 patients operated due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia and the Institute for Oncology and Radiology of Serbia from January 2002 to December 2010, who developed LR during the 5-year follow-up. Diagnostic methods and surgical approaches were standard, defined by protocols. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analysis showed significant difference in DFS and LR incidence in first 2 postoperative years related to primary tumor size and stage. Patients with T1 tumors (vs T2 vs T3), as well as in earlier disease stage, had significantly longer DFS. LR in the first and second year after primary tumor operation occurred more frequently with larger primary tumors. Significant correlation was registered between LR operability and primary tumor size, as well as LR operability and primary tumor stage. CONCLUSIONS: This research highlights size of the primary tumor as independent prognostic factor for patients with NSCLC. The likelihood of LR increases with larger primary tumor and higher primary tumor stages, while DFS decreases. Because larger tumors are more frequently understaged, with occult mediastinal metastases, their LR is not possible to be surgically treated. FAU - Stojiljkovic, Dejan AU - Stojiljkovic D AD - Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. FAU - Santrac, Nada AU - Santrac N FAU - Stojiljkovic, Tanja AU - Stojiljkovic T FAU - Miletic, Nebojsa AU - Miletic N FAU - Gavrilovic, Dusica AU - Gavrilovic D LA - eng PT - Journal Article PT - Multicenter Study PL - Greece TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - Adenocarcinoma of lung SB - IM MH - Adenocarcinoma/mortality/*pathology/surgery MH - Adult MH - Aged MH - Carcinoma, Adenosquamous/mortality/*pathology/surgery MH - Carcinoma, Non-Small-Cell Lung/mortality/*pathology/surgery MH - Disease-Free Survival MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/mortality/*pathology/surgery MH - Male MH - Middle Aged MH - Neoplasm Grading MH - *Neoplasm Recurrence, Local MH - Neoplasm Staging MH - Pneumonectomy MH - Risk Factors MH - Serbia MH - Time Factors MH - Treatment Outcome MH - *Tumor Burden EDAT- 2015/03/18 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/18 06:00 PST - ppublish SO - J BUON. 2015 Jan-Feb;20(1):166-72. PMID- 25778309 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150430 IS - 1107-0625 (Print) IS - 1107-0625 (Linking) VI - 20 IP - 1 DP - 2015 Jan-Feb TI - Detection of epidermal growth factor receptor mutation in non-small-cell lung carcinoma using cytological and histological specimens. PG - 142-5 AB - PURPOSE: Epidermal growth factor receptor (EGFR) mutations are prerequisites for the targeted therapy with anti-EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung carcinomas (NSCLCs). In patients with advanced-stage NSCLC, sometimes cytological specimens, including those from fine-needle aspiration cytology (FNAC) and pleural effusion, are the only materials for mutation analysis. The purpose of this study was to compare the results of EGFR mutation detection from cytological specimens and histological samples and to evaluate the difference between them, therefore to assess if cell block is a valid source for detection of EGFR mutation. METHODS: Forty-seven samples from advanced-stage NSCLCs were obtained with individually matched cell blocks (CBs) from FNAC (29 cases) or pleural fluid (18 cases), and formalin-fixed paraffin-embedded (FFPE) blocks from biopsy (34 cases) or surgical excision (13 cases). CBs and FFPE blocks were simultaneously tested for EGFR hot mutations in exons 18, 19, 20 and 21 by polymerase chain reaction (PCR)-direct sequencing and amplification refractory mutation system (ARMS)-PCR. RESULTS: EGFR mutations were identified in 18/47 (38.3%) or 21/47 (44.7%) cases using CBs and 16/47 (34.0%) or 19/47 (40.4%) using FPPE blocks by PCR-direct sequencing or ARMS-PCR, respectively. The incidence of EGFR mutation was not statistically significant between CBs and FFPE blocks using PCR-direct sequencing or ARMS-PCR (p=0.668 or p=0.677, respectively). CONCLUSION: Our study suggests that cytological specimens are optimal for advanced NSCLC. The successful use of these non-invasive specimens in molecular pathology is beneficial for patients requiring targeted therapy. FAU - Xu, Haimiao AU - Xu H AD - Department of Pathology, Zhejiang Cancer Hospital, Hangzhou 310022, China. FAU - Sun, Wenyong AU - Sun W FAU - Zhang, Gu AU - Zhang G FAU - Cheng, Yue AU - Cheng Y LA - eng PT - Comparative Study PT - Journal Article PL - Greece TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (Tumor Markers, Biological) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Adult MH - Biopsy, Fine-Needle MH - Carcinoma, Non-Small-Cell Lung/enzymology/*genetics/pathology MH - DNA Mutational Analysis/*methods MH - Exons MH - Female MH - Humans MH - Lung Neoplasms/enzymology/*genetics/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Neoplasm Staging MH - Paraffin Embedding MH - Pleural Effusion, Malignant/pathology MH - Polymerase Chain Reaction MH - Predictive Value of Tests MH - Receptor, Epidermal Growth Factor/*genetics MH - Specimen Handling/*methods MH - Tissue Fixation MH - Tumor Markers, Biological/*genetics EDAT- 2015/03/18 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/18 06:00 PST - ppublish SO - J BUON. 2015 Jan-Feb;20(1):142-5. PMID- 25778308 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150430 IS - 1107-0625 (Print) IS - 1107-0625 (Linking) VI - 20 IP - 1 DP - 2015 Jan-Feb TI - EGFR mutations in patients with non small-cell lung cancer in Bulgaria and treatment with gefitinib. PG - 136-41 AB - PURPOSE: To evaluate the EGFR mutations in non small cell lung cancer (NSCLC) patients in Bulgaria, as well as to summarize the outcomes of patients with EGFR mutations, treated with gefitinib as first- or subsequent-line therapy. METHODS: From January 2010 to March 2012 tumor samples from773 NSCLC patients were evaluated for EGFR mutations. RESULTS: Seventy-one mutations were found and 34 patients were treated with gefitinib. Complete remission (CR) was achieved in 2 patients (6.9%), partial remission (PR) in 11 (37.9%), stable disease (SD) in 13 (44.8%), and disease progression (PD) in 3 (10.3%). Higher objective response rate was seen in women and in never-smokers.The mean progression-free survival (PFS) was 11.1 months (95% CI 9.1-13.1), registered in 29 patients (median PFS 10 months ; 95% CI 8.9-11.1).Tolerability to gefitinib was acceptable, with prevalence of skin toxicity, and it did not lead to any significant decline of the patients' quality of life. CONCLUSION: This is the first study in Bulgaria to evaluate EGFR mutations in NSCLC patients,which were encountered in 9.4% of the studied population. The present study confirms the benefits of first- and subsequent-lines of gefitinib for the treatment of this patient group. Our data give grounds for the conclusion that gefitinib is an effective and well-tolerated therapeutic option for patients with locally advanced and metastatic NSCLC harboring EGFR mutations. FAU - Damyanov, Danail AU - Damyanov D AD - Clinic of Medical Oncology, Specialized Oncology Hospital, Sofia, Bulgaria. FAU - Koynov, Krassimir AU - Koynov K FAU - Naseva, Emilia AU - Naseva E FAU - Bichev, Stoyan AU - Bichev S LA - eng PT - Journal Article PL - Greece TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - S65743JHBS (gefitinib) SB - IM MH - Aged MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Bulgaria MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/*genetics/pathology MH - DNA Mutational Analysis MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Individualized Medicine MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/enzymology/*genetics/pathology MH - Male MH - Middle Aged MH - Molecular Targeted Therapy MH - *Mutation MH - Patient Selection MH - Phenotype MH - Predictive Value of Tests MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Quinazolines/adverse effects/*therapeutic use MH - Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*genetics MH - Remission Induction MH - Risk Factors MH - Time Factors MH - Treatment Outcome EDAT- 2015/03/18 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/18 06:00 PST - ppublish SO - J BUON. 2015 Jan-Feb;20(1):136-41. PMID- 25773859 OWN - NLM STAT- MEDLINE DA - 20150316 DCOM- 20150512 IS - 1513-7368 (Print) IS - 1513-7368 (Linking) VI - 16 IP - 5 DP - 2015 TI - Careful diagnosis of aortic invasion in patients with lung cancer using modern diagnostic imaging. PG - 2105-3 FAU - Uramoto, Hidetaka AU - Uramoto H AD - Divisions of Thoracic Surgery, Saitama Cancer Center, Saitama, Japan Email: hidetaka@cancer-c.pref.saitama.jp. FAU - Kinoshita, Hiroyasu AU - Kinoshita H LA - eng PT - Comment PT - Letter PL - Thailand TA - Asian Pac J Cancer Prev JT - Asian Pacific journal of cancer prevention : APJCP JID - 101130625 SB - IM CON - Asian Pac J Cancer Prev. 2014;15(6):2465-72. PMID: 24761848 MH - Adenocarcinoma/*mortality MH - Carcinoma, Large Cell/*mortality MH - Carcinoma, Non-Small-Cell Lung/*mortality MH - Carcinoma, Squamous Cell/*mortality MH - Female MH - Humans MH - Lung Neoplasms/*mortality MH - Male MH - Neoplasm Staging/*standards EDAT- 2015/03/17 06:00 MHDA- 2015/05/13 06:00 CRDT- 2015/03/17 06:00 PST - ppublish SO - Asian Pac J Cancer Prev. 2015;16(5):2105-3. PMID- 25772453 OWN - NLM STAT- MEDLINE DA - 20150316 DCOM- 20150430 IS - 0890-9091 (Print) IS - 0890-9091 (Linking) VI - 29 IP - 3 DP - 2015 Mar TI - Minimally invasive resection of early lung cancers. PG - 160-6 LID - 204255 [pii] AB - Low-dose computed tomography (LDCT) screening decreases lung cancer mortality in high-risk individuals and has now been approved and adopted for lung cancer screening in the United States. As more LDCT lung cancer screening programs are implemented, more patients with early-stage lung cancer who could benefit from surgical intervention will be identified. Although lobectomy currently remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), thoracic surgeons are increasingly adopting minimally invasive surgery via thoracoscopy as a viable-and perhaps even preferred-approach for select lung cancer resections. Video-assisted thoracic surgery (VATS) lobectomy has been associated with decreased perioperative morbidity, and similar rates of locoregional recurrence and cancer-free survival can be achieved compared with the standard open surgical procedure. However, as lung cancers are detected at earlier stages, the optimal extent of lung resection for long-term cure continues to be investigated. For patients with very small-sized lung tumors and indolent lesions, cancer-free survival may not necessarily be compromised by undergoing less invasive approaches that intentionally resect less lung tissue, such as sublobar resections (eg, segmentectomy and wedge resection). This review looks at the current data and guidelines for thoracoscopic resection of stage I NSCLC and discusses the potential for limited lung resection in patients with the disease. FAU - Cheng, Aaron M AU - Cheng AM FAU - Wood, Douglas E AU - Wood DE LA - eng PT - Journal Article PT - Review PL - United States TA - Oncology (Williston Park) JT - Oncology (Williston Park, N.Y.) JID - 8712059 SB - IM CIN - Oncology (Williston Park). 2015 Mar;29(3):149. PMID: 25772452 CIN - Oncology (Williston Park). 2015 Mar;29(3):166; 168. PMID: 25772454 MH - Carcinoma, Non-Small-Cell Lung/mortality/pathology/radiography/*surgery MH - Disease-Free Survival MH - Early Detection of Cancer/methods MH - Humans MH - Lung Neoplasms/mortality/pathology/radiography/*surgery MH - Neoplasm Staging MH - Pneumonectomy/adverse effects/*methods/mortality MH - Predictive Value of Tests MH - Risk Factors MH - *Thoracic Surgery, Video-Assisted/adverse effects/mortality MH - Time Factors MH - Tomography, X-Ray Computed MH - Treatment Outcome MH - Tumor Burden EDAT- 2015/03/17 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/17 06:00 AID - 204255 [pii] PST - ppublish SO - Oncology (Williston Park). 2015 Mar;29(3):160-6. PMID- 25765070 OWN - NLM STAT- MEDLINE DA - 20150403 DCOM- 20150429 LR - 20150514 IS - 1095-9203 (Electronic) IS - 0036-8075 (Linking) VI - 348 IP - 6230 DP - 2015 Apr 3 TI - Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. PG - 124-8 LID - 10.1126/science.aaa1348 [doi] AB - Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti-PD-1 therapy. CI - Copyright (c) 2015, American Association for the Advancement of Science. FAU - Rizvi, Naiyer A AU - Rizvi NA AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. chant@mskcc.org. FAU - Hellmann, Matthew D AU - Hellmann MD AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. FAU - Snyder, Alexandra AU - Snyder A AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Kvistborg, Pia AU - Kvistborg P AD - Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. FAU - Makarov, Vladimir AU - Makarov V AD - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Havel, Jonathan J AU - Havel JJ AD - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Lee, William AU - Lee W AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Yuan, Jianda AU - Yuan J AD - Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Wong, Phillip AU - Wong P AD - Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Ho, Teresa S AU - Ho TS AD - Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Miller, Martin L AU - Miller ML AD - Computation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Rekhtman, Natasha AU - Rekhtman N AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Moreira, Andre L AU - Moreira AL AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Ibrahim, Fawzia AU - Ibrahim F AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Bruggeman, Cameron AU - Bruggeman C AD - Department of Mathematics, Columbia University, New York, NY, 10027, USA. FAU - Gasmi, Billel AU - Gasmi B AD - Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Zappasodi, Roberta AU - Zappasodi R AD - Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Maeda, Yuka AU - Maeda Y AD - Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Sander, Chris AU - Sander C AD - Computation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Garon, Edward B AU - Garon EB AD - David Geffen School of Medicine at UCLA, 2825 Santa Monica Boulevard, Suite 200, Santa Monica, CA 90404, USA. FAU - Merghoub, Taha AU - Merghoub T AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Wolchok, Jedd D AU - Wolchok JD AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY, 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Schumacher, Ton N AU - Schumacher TN AD - Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. FAU - Chan, Timothy A AU - Chan TA AD - Weill Cornell Medical College, New York, NY, 10065, USA. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. chant@mskcc.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150312 PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - CD8-Positive T-Lymphocytes/immunology MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/immunology MH - Cohort Studies MH - DNA Repair/genetics MH - Disease-Free Survival MH - Drug Resistance, Neoplasm/*genetics MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics/immunology MH - Mutation MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors MH - Smoking/genetics EDAT- 2015/03/15 06:00 MHDA- 2015/04/30 06:00 CRDT- 2015/03/14 06:00 PHST- 2014/10/21 [received] PHST- 2015/02/27 [accepted] PHST- 2015/03/12 [aheadofprint] AID - science.aaa1348 [pii] AID - 10.1126/science.aaa1348 [doi] PST - ppublish SO - Science. 2015 Apr 3;348(6230):124-8. doi: 10.1126/science.aaa1348. Epub 2015 Mar 12. PMID- 25752401 OWN - NLM STAT- MEDLINE DA - 20150310 DCOM- 20150430 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 91 IP - 4 DP - 2015 Mar 15 TI - Individualized positron emission tomography-based isotoxic accelerated radiation therapy is cost-effective compared with conventional radiation therapy: a model-based evaluation. PG - 857-65 LID - 10.1016/j.ijrobp.2014.12.012 [doi] LID - S0360-3016(14)04487-3 [pii] AB - PURPOSE: To evaluate long-term health effects, costs, and cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose CT-based radiation therapy treatment (CRT) in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Our analysis uses a validated decision model, based on data of 200 NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use, costs, and utilities were obtained from the Maastro Clinic and the literature. Primary model outcomes were the difference in life-years (LYs), quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness and cost/utility ratio (ICER and ICUR) of PET-ART versus CRT. Model outcomes were obtained from averaging the predictions for 50,000 simulated patients. A probabilistic sensitivity analysis and scenario analyses were carried out. RESULTS: The average incremental costs per patient of PET-ART were euro569 (95% confidence interval [CI] euro-5327-euro6936) for 0.42 incremental LYs (95% CI 0.19-0.61) and 0.33 QALYs gained (95% CI 0.13-0.49). The base-case scenario resulted in an ICER of euro1360 per LY gained and an ICUR of euro1744 per QALY gained. The probabilistic analysis gave a 36% probability that PET-ART improves health outcomes at reduced costs and a 64% probability that PET-ART is more effective at slightly higher costs. CONCLUSION: On the basis of the available data, individualized PET-ART for NSCLC seems to be cost-effective compared with CRT. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Bongers, Mathilda L AU - Bongers ML AD - Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ml.bongers@vumc.nl. FAU - Coupe, Veerle M H AU - Coupe VM AD - Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. FAU - De Ruysscher, Dirk AU - De Ruysscher D AD - Radiation Oncology University Hospitals Leuven/KU Leuven, Leuven, Belgium; Department of Radiation Oncology, GROW Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Oberije, Cary AU - Oberije C AD - Department of Radiation Oncology, GROW Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Lambin, Philippe AU - Lambin P AD - Department of Radiation Oncology, GROW Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Uyl-de Groot, Cornelia A AU - Uyl-de Groot CA AD - Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 SB - IM MH - Carcinoma, Non-Small-Cell Lung/pathology/*radiotherapy MH - Confidence Intervals MH - Cost-Benefit Analysis MH - Disease Progression MH - Health Status MH - Humans MH - Individualized Medicine/adverse effects/*economics MH - Lung Neoplasms/pathology/*radiotherapy MH - Positron-Emission Tomography/adverse effects/*economics MH - Quality of Life MH - Quality-Adjusted Life Years MH - Radiotherapy Dosage MH - Sensitivity and Specificity MH - Uncertainty EDAT- 2015/03/11 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/11 06:00 PHST- 2014/01/15 [received] PHST- 2014/12/03 [revised] PHST- 2014/12/08 [accepted] AID - S0360-3016(14)04487-3 [pii] AID - 10.1016/j.ijrobp.2014.12.012 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2015 Mar 15;91(4):857-65. doi: 10.1016/j.ijrobp.2014.12.012. PMID- 25752391 OWN - NLM STAT- MEDLINE DA - 20150310 DCOM- 20150430 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 91 IP - 4 DP - 2015 Mar 15 TI - Safety and palliative efficacy of single-dose 8-Gy reirradiation for painful local failure in patients with stage IV non-small cell lung cancer previously treated with radical chemoradiation therapy. PG - 774-80 LID - 10.1016/j.ijrobp.2014.12.010 [doi] LID - S0360-3016(14)04485-X [pii] AB - PURPOSE: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. PATIENTS AND METHODS: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a >/=2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. RESULTS: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. CONCLUSIONS: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Topkan, Erkan AU - Topkan E AD - Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana, Turkey. Electronic address: docdretopkan@gmail.com. FAU - Yildirim, Berna Akkus AU - Yildirim BA AD - Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana, Turkey. FAU - Guler, Ozan Cem AU - Guler OC AD - Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana, Turkey. FAU - Parlak, Cem AU - Parlak C AD - Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana, Turkey. FAU - Pehlivan, Berrin AU - Pehlivan B AD - Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, and American Hospital, University of Texas MD Anderson Radiation Treatment Center, Istanbul, Turkey. FAU - Selek, Ugur AU - Selek U AD - Medstar Hospital, Department of Radiation Oncology, Antalya, Turkey. LA - eng PT - Journal Article PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 SB - IM MH - Adenocarcinoma/mortality/pathology/*radiotherapy/secondary MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/pathology/*radiotherapy/secondary MH - Carcinoma, Squamous Cell/mortality/pathology/*radiotherapy/secondary MH - Chemoradiotherapy MH - Chest Pain/etiology/*radiotherapy MH - Esophagitis/etiology MH - Female MH - Humans MH - Lung Neoplasms/mortality/pathology/*radiotherapy MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Pain Management/methods MH - Pain Measurement MH - Palliative Care/methods MH - Pneumonia/etiology MH - Radiotherapy Dosage MH - Radiotherapy, Conformal MH - Retreatment/adverse effects/methods/mortality MH - Retrospective Studies MH - Treatment Outcome EDAT- 2015/03/11 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/11 06:00 PHST- 2014/10/11 [received] PHST- 2014/12/01 [revised] PHST- 2014/12/04 [accepted] AID - S0360-3016(14)04485-X [pii] AID - 10.1016/j.ijrobp.2014.12.010 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2015 Mar 15;91(4):774-80. doi: 10.1016/j.ijrobp.2014.12.010. PMID- 25752390 OWN - NLM STAT- MEDLINE DA - 20150310 DCOM- 20150430 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 91 IP - 4 DP - 2015 Mar 15 TI - Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival. PG - 765-73 LID - 10.1016/j.ijrobp.2014.12.028 [doi] LID - S0360-3016(14)04528-3 [pii] AB - PURPOSE: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. METHODS AND MATERIALS: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. RESULTS: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. CONCLUSIONS: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Varlotto, John M AU - Varlotto JM AD - Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts. Electronic address: john.varlotto@umassmemorial.org. FAU - Yao, Aaron N AU - Yao AN AD - Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia. FAU - DeCamp, Malcolm M AU - DeCamp MM AD - Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois; Northwestern University School of Medicine, Chicago, Illinois. FAU - Ramakrishna, Satvik AU - Ramakrishna S AD - Northwestern University School of Medicine, Chicago, Illinois. FAU - Recht, Abe AU - Recht A AD - Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. FAU - Flickinger, John AU - Flickinger J AD - Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. FAU - Andrei, Adin AU - Andrei A AD - Northwestern University, Chicago, Illinois. FAU - Reed, Michael F AU - Reed MF AD - Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Heart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania. FAU - Toth, Jennifer W AU - Toth JW AD - Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania. FAU - Fizgerald, Thomas J AU - Fizgerald TJ AD - Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts. FAU - Higgins, Kristin AU - Higgins K AD - Department of Radiation Oncology, Emory University, Atlanta, Georgia. FAU - Zheng, Xiao AU - Zheng X AD - Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia. FAU - Shelkey, Julie AU - Shelkey J AD - Department of Anesthesiology, Columbia University, New York, New York. FAU - Medford-Davis, Laura N AU - Medford-Davis LN AD - Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas. FAU - Belani, Chandra AU - Belani C AD - Pennsylvania State University-Hershey Cancer Institute, Hershey, Pennsylvania. FAU - Kelsey, Christopher R AU - Kelsey CR AD - Department of Radiation Oncology, Duke University Cancer Institute, Durham, North Carolina. LA - eng GR - 2R25CA093423/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 SB - IM MH - Aged MH - Carcinoma, Non-Small-Cell Lung/mortality/*pathology/secondary/*surgery MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/mortality/*pathology/*surgery MH - Lymph Nodes/*pathology MH - Lymphatic Metastasis/pathology MH - Male MH - Middle Aged MH - *Neoplasm Recurrence, Local/mortality MH - Retrospective Studies EDAT- 2015/03/11 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/03/11 06:00 PHST- 2014/07/28 [received] PHST- 2014/12/08 [revised] PHST- 2014/12/11 [accepted] AID - S0360-3016(14)04528-3 [pii] AID - 10.1016/j.ijrobp.2014.12.028 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2015 Mar 15;91(4):765-73. doi: 10.1016/j.ijrobp.2014.12.028. PMID- 25750344 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150505 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 35 IP - 3 DP - 2015 Mar TI - Associations between driver gene mutations and cytotoxic chemosensitivity in patients with non-small cell lung cancer. PG - 1791-6 AB - BACKGROUND/AIM: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement often have a better prognosis when they are treated with specific inhibitors than when treated with cytotoxic agents. However, the associations between gene mutations and cytotoxic chemosensitivity are still unclear. The objective of the present study was to identify which clinicopathological factors, including genetic mutations, influence chemosensitivity, determined using the succinate dehydrogenase inhibition (SDI) test in patients with NSCLC. MATERIALS AND METHODS: The chemosensitivity of tumor tissues from 96 patients with NSCLC who underwent surgical resection was evaluated using the SDI test. RESULTS: In patients with adenocarcinoma, tumors with EGFR gene mutations were significantly more sensitive to 5-fluorouracil (5-FU) than tumors without EGFR gene mutations (p<0.0149). CONCLUSION: Our data suggest that patients with adenocarcinoma harboring EGFR gene mutations may be susceptible to 5-FU. CI - Copyright(c) 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Morodomi, Yosuke AU - Morodomi Y AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Department of Innovative Applied Oncology, Kyushu University, Fukuoka, Japan yo-suke@surg2.med.kyushu-u.ac.jp. FAU - Okamoto, Tatsuro AU - Okamoto T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Kohno, Mikihiro AU - Kohno M AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Katsura, Masakazu AU - Katsura M AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Takada, Kazuki AU - Takada K AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Suzuki, Yuzo AU - Suzuki Y AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Fujishita, Takatoshi AU - Fujishita T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Kitahara, Hirokazu AU - Kitahara H AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shimamatsu, Shinichiro AU - Shimamatsu S AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Yoshida, Tsukihisa AU - Yoshida T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Tagawa, Tetsuzo AU - Tagawa T AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Okano, Shinji AU - Okano S AD - Department of Innovative Applied Oncology, Kyushu University, Fukuoka, Japan. FAU - Maehara, Yoshihiko AU - Maehara Y AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (EML4-ALK fusion protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics MH - Female MH - Fluorouracil/therapeutic use MH - Gene Rearrangement MH - Humans MH - Lung Neoplasms/drug therapy/*genetics MH - Male MH - Middle Aged MH - *Mutation MH - Oncogene Proteins, Fusion/genetics MH - Receptor, Epidermal Growth Factor/*genetics OTO - NOTNLM OT - Non-small cell lung cancer OT - anaplastic lymphoma kinase OT - chemosensitivity OT - epidermal growth factor receptor EDAT- 2015/03/10 06:00 MHDA- 2015/05/06 06:00 CRDT- 2015/03/10 06:00 AID - 35/3/1791 [pii] PST - ppublish SO - Anticancer Res. 2015 Mar;35(3):1791-6. PMID- 25750343 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150505 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 35 IP - 3 DP - 2015 Mar TI - Role of salvage stereotactic body radiation therapy in post-surgical loco-regional recurrence in a selected population of non-small cell lung cancer patients. PG - 1783-9 AB - AIM: This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed. PATIENTS AND METHODS: Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments. RESULTS: Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity. CONCLUSION: Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies. CI - Copyright(c) 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Agolli, Linda AU - Agolli L AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy linda.agolli@gmail.com. FAU - Valeriani, Maurizio AU - Valeriani M AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Carnevale, Alessia AU - Carnevale A AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Falco, Teresa AU - Falco T AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Bracci, Stefano AU - Bracci S AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - De Sanctis, Vitaliana AU - De Sanctis V AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Minniti, Giuseppe AU - Minniti G AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Enrici, Riccardo Maurizi AU - Enrici RM AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. FAU - Osti, Mattia Falchetto AU - Osti MF AD - Institute of Radiation Oncology, Sapienza University, Sant'Andrea Hospital, Rome, Italy. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/*surgery MH - Female MH - Humans MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/mortality/*surgery MH - *Radiosurgery/adverse effects MH - *Salvage Therapy OTO - NOTNLM OT - Salvage stereotactic radiotherapy OT - local control OT - non-small cell lung cancer OT - post-surgical recurrence EDAT- 2015/03/10 06:00 MHDA- 2015/05/06 06:00 CRDT- 2015/03/10 06:00 AID - 35/3/1783 [pii] PST - ppublish SO - Anticancer Res. 2015 Mar;35(3):1783-9. PMID- 25750330 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150505 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 35 IP - 3 DP - 2015 Mar TI - Vinorelbine and cisplatin in patients with advanced non-small cell lung cancer with interstitial pneumonia. PG - 1697-701 AB - AIM: The aim of the present study was to investigate the efficacy and tolerability of vinorelbine and cisplatin for the treatment of patients with advanced (stage IIIB, IV or relapse) non-small cell lung cancer (NSCLC) with interstitial pneumonia (IP). PATIENTS AND METHODS: A total of 67 patients treated with vinorelbine and cisplatin as a first-line chemo therapy between January 2002 and December 2013 were retrospectively reviewed. RESULTS: The overall response rate was 34.3% [95% confidence interval (CI)=22.9%-45.7%). The median progression-free survival, median overall survival, and 1-year survival rates were 3.7 months (95% CI=3.1-4.3 months), 7.4 months (95% CI=5.4-9.4 months), and 22.4% (95% CI=12.4%-32.4%), respectively. The incidence of acute exacerbation of IP following first-line chemotherapy was 10.4%. CONCLUSION: The combination of vinorelbine and cisplatin is a feasible treatment option for advanced NSCLC patients with IP, after careful consideration of the potential risks and benefits on an individual basis. CI - Copyright(c) 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Watanabe, Naohiro AU - Watanabe N AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Niho, Seiji AU - Niho S AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan siniho@east.ncc.go.jp. FAU - Kirita, Keisuke AU - Kirita K AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Umemura, Shigeki AU - Umemura S AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Matsumoto, Shingo AU - Matsumoto S AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Yoh, Kiyotaka AU - Yoh K AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Ohmatsu, Hironobu AU - Ohmatsu H AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Goto, Koichi AU - Goto K AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 5V9KLZ54CY (Vinblastine) RN - Q20Q21Q62J (Cisplatin) RN - Q6C979R91Y (vinorelbine) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality MH - Cisplatin/administration & dosage/adverse effects MH - Female MH - Humans MH - Lung Diseases, Interstitial/*complications MH - Lung Neoplasms/*drug therapy/mortality MH - Male MH - Middle Aged MH - Retrospective Studies MH - Vinblastine/administration & dosage/adverse effects/analogs & derivatives OTO - NOTNLM OT - Acute exacerbation OT - cisplatin OT - interstitial pneumonia OT - non-small cell lung cancer OT - vinorelbine EDAT- 2015/03/10 06:00 MHDA- 2015/05/06 06:00 CRDT- 2015/03/10 06:00 AID - 35/3/1697 [pii] PST - ppublish SO - Anticancer Res. 2015 Mar;35(3):1697-701. PMID- 25732468 OWN - NLM STAT- MEDLINE DA - 20150303 DCOM- 20150512 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 147 IP - 3 DP - 2015 Mar TI - Response. PG - e122-3 LID - 10.1378/chest.14-3079 [doi] FAU - Dooms, Christophe AU - Dooms C FAU - Tournoy, Kurt AU - Tournoy K LA - eng PT - Comment PT - Letter PL - United States TA - Chest JT - Chest JID - 0231335 SB - AIM SB - IM CON - Chest. 2015 Mar;147(3):e122. PMID: 25732467 CON - Chest. 2015 Jan;147(1):209-15. PMID: 25211526 MH - Carcinoma, Non-Small-Cell Lung/*diagnosis MH - Female MH - Humans MH - Lung Neoplasms/*ultrasonography MH - Lymph Nodes/*ultrasonography MH - Male MH - Neoplasm Staging/*methods MH - Ultrasonography, Interventional/*methods EDAT- 2015/03/04 06:00 MHDA- 2015/05/13 06:00 CRDT- 2015/03/04 06:00 AID - 2173454 [pii] AID - 10.1378/chest.14-3079 [doi] PST - ppublish SO - Chest. 2015 Mar;147(3):e122-3. doi: 10.1378/chest.14-3079. PMID- 25732467 OWN - NLM STAT- MEDLINE DA - 20150303 DCOM- 20150512 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 147 IP - 3 DP - 2015 Mar TI - Endosonographic staging for N1 disease. PG - e122 LID - 10.1378/chest.14-2577 [doi] FAU - Annema, Jouke T AU - Annema JT LA - eng PT - Comment PT - Letter PL - United States TA - Chest JT - Chest JID - 0231335 SB - AIM SB - IM CON - Chest. 2015 Jan;147(1):209-15. PMID: 25211526 CIN - Chest. 2015 Mar;147(3):e122-3. PMID: 25732468 MH - Carcinoma, Non-Small-Cell Lung/*diagnosis MH - Female MH - Humans MH - Lung Neoplasms/*ultrasonography MH - Lymph Nodes/*ultrasonography MH - Male MH - Neoplasm Staging/*methods MH - Ultrasonography, Interventional/*methods EDAT- 2015/03/04 06:00 MHDA- 2015/05/13 06:00 CRDT- 2015/03/04 06:00 AID - 2173453 [pii] AID - 10.1378/chest.14-2577 [doi] PST - ppublish SO - Chest. 2015 Mar;147(3):e122. doi: 10.1378/chest.14-2577. PMID- 25726880 OWN - NLM STAT- MEDLINE DA - 20150302 DCOM- 20150427 IS - 1097-685X (Electronic) IS - 0022-5223 (Linking) VI - 149 IP - 2 DP - 2015 Feb TI - Prehabilitation: Prevention is better than cure. PG - 574-5 LID - 10.1016/j.jtcvs.2014.10.078 [doi] LID - S0022-5223(14)01587-6 [pii] FAU - Dickinson, Karen J AU - Dickinson KJ AD - Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minn. FAU - Blackmon, Shanda H AU - Blackmon SH AD - Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minn. Electronic address: Blackmon.shanda@mayo.edu. LA - eng PT - Comment PT - Editorial DEP - 20141022 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 SB - AIM SB - IM CON - J Thorac Cardiovasc Surg. 2015 Feb;149(2):569-73. PMID: 25451483 MH - Carcinoma, Non-Small-Cell Lung/*physiopathology/*therapy MH - *Chemoradiotherapy MH - Female MH - Humans MH - Lung Neoplasms/*physiopathology/*therapy MH - Male EDAT- 2015/03/03 06:00 MHDA- 2015/04/29 06:00 CRDT- 2015/03/03 06:00 PHST- 2014/10/16 [received] PHST- 2014/10/17 [accepted] PHST- 2014/10/22 [aheadofprint] AID - S0022-5223(14)01587-6 [pii] AID - 10.1016/j.jtcvs.2014.10.078 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2015 Feb;149(2):574-5. doi: 10.1016/j.jtcvs.2014.10.078. Epub 2014 Oct 22. PMID- 25715252 OWN - NLM STAT- MEDLINE DA - 20150226 DCOM- 20150428 IS - 1536-5964 (Electronic) IS - 0025-7974 (Linking) VI - 94 IP - 8 DP - 2015 Feb TI - High incidence of EGFR mutations in pneumonic-type non-small cell lung cancer. PG - e540 LID - 10.1097/MD.0000000000000540 [doi] AB - To retrospectively identify computed tomography (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected pneumonic-type lung cancer (P-LC). A total of 953 consecutive patients with surgically resected lung cancer in the First Affiliated Hospital of Guangzhou Medical University from August 2011 to August 2013 were studied. The CT manifestations were reevaluated independently by 2 radiologists. The presence of pneumonic-type consolidation with pathological confirmed non-small lung cancer (NSCLC) was defined as P-LC. EGFR mutation was determined by direct DNA sequencing or amplification refractory mutation system-PCR. EGFR mutation rates as well as clinical and pathological manifestations between P-LC and control lung cancer patients were compared. P-LC was diagnosed in 85 patients. Among these patients, 82 were adenocarcinoma (including 78 cases of invasive adenocarcinoma and 4 cases of microinvasive adenocarcinoma), 2 were squamous carcinoma and 1 was other type. P-LC occurred more frequently in female (58.8% vs 37.1%, P < 0.01), nonsmoking (76.5% vs 56.5%, P = 0.001) and adenocarcinoma (58.8% vs 37.1%, P < 0.01) patients. Moreover, EGFR mutations were found in 39 of 52 P-LC patients (75%) and 263 of 542 non-P-LC NSCLC patients (48.5%). However, no difference was found on the mutation sites of EGFR. Histological type, sex, and radiological manifestations (P-LC vs non-P-LC) but not smoking or sequencing method can be served as the independent predictor of EGFR mutations. P-LC patients showed a significant higher incidence of EGFR mutations, which was independent of sex, histological type, and smoking history. The patients with imaging manifestation of pneumonic-type consolidation are highly suggested to perform EGFR mutation analysis to guide the sequential treatment. FAU - Liu, Jun AU - Liu J AD - From the Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University (JL, JS, CY, PH, YG, WL, JH); Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease (JL, JS, CY, PH, YG, WL, JH); Department of Pathology (PH); and Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (YG). FAU - Shen, Jianfei AU - Shen J FAU - Yang, Chenglin AU - Yang C FAU - He, Ping AU - He P FAU - Guan, Yubao AU - Guan Y FAU - Liang, Wenhua AU - Liang W FAU - He, Jianxing AU - He J LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R SB - AIM SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*genetics/pathology MH - Child MH - Female MH - *Genes, erbB-1 MH - Humans MH - Lung/pathology MH - Lung Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Retrospective Studies MH - Young Adult EDAT- 2015/02/26 06:00 MHDA- 2015/04/29 06:00 CRDT- 2015/02/26 06:00 AID - 10.1097/MD.0000000000000540 [doi] AID - 00005792-201502040-00005 [pii] PST - ppublish SO - Medicine (Baltimore). 2015 Feb;94(8):e540. doi: 10.1097/MD.0000000000000540. PMID- 25704436 OWN - NLM STAT- MEDLINE DA - 20150310 DCOM- 20150511 IS - 1474-5488 (Electronic) IS - 1470-2045 (Linking) VI - 16 IP - 3 DP - 2015 Mar TI - Nivolumab for advanced squamous cell lung cancer: what are the next steps? PG - 234-5 LID - 10.1016/S1470-2045(15)70074-4 [doi] LID - S1470-2045(15)70074-4 [pii] FAU - de Mello, Ramon Andrade AU - de Mello RA AD - Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; Department of Medical Oncology, Portuguese Oncology Institute, Porto, Portugal. Electronic address: ramello@ualg.pt. FAU - Pousa, Ines AU - Pousa I AD - Department of Medical Oncology, Portuguese Oncology Institute, Porto, Portugal. FAU - Pereira, Deolinda AU - Pereira D AD - Department of Medical Oncology, Portuguese Oncology Institute, Porto, Portugal. LA - eng PT - Comment PT - Journal Article DEP - 20150220 PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (nivolumab) SB - IM CON - Lancet Oncol. 2015 Mar;16(3):257-65. PMID: 25704439 MH - Antibodies, Monoclonal/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors EDAT- 2015/02/24 06:00 MHDA- 2015/05/12 06:00 CRDT- 2015/02/24 06:00 PHST- 2015/02/20 [aheadofprint] AID - S1470-2045(15)70074-4 [pii] AID - 10.1016/S1470-2045(15)70074-4 [doi] PST - ppublish SO - Lancet Oncol. 2015 Mar;16(3):234-5. doi: 10.1016/S1470-2045(15)70074-4. Epub 2015 Feb 20. PMID- 25701169 OWN - NLM STAT- MEDLINE DA - 20150310 DCOM- 20150511 IS - 1474-5488 (Electronic) IS - 1470-2045 (Linking) VI - 16 IP - 3 DP - 2015 Mar TI - Necitumumab for patients with non-squamous NSCLC: uninspiring results. PG - 246-7 LID - 10.1016/S1470-2045(15)70059-8 [doi] LID - S1470-2045(15)70059-8 [pii] FAU - Zhou, Fei AU - Zhou F AD - Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. FAU - Zhou, Caicun AU - Zhou C AD - Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: caicunzhoudr@163.com. LA - eng PT - Comment PT - Journal Article DEP - 20150218 PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 SB - IM CON - Lancet Oncol. 2015 Mar;16(3):328-37. PMID: 25701171 MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male EDAT- 2015/02/24 06:00 MHDA- 2015/05/12 06:00 CRDT- 2015/02/22 06:00 PHST- 2015/02/18 [aheadofprint] AID - S1470-2045(15)70059-8 [pii] AID - 10.1016/S1470-2045(15)70059-8 [doi] PST - ppublish SO - Lancet Oncol. 2015 Mar;16(3):246-7. doi: 10.1016/S1470-2045(15)70059-8. Epub 2015 Feb 18. PMID- 25667288 OWN - NLM STAT- MEDLINE DA - 20150319 DCOM- 20150518 LR - 20150319 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 9 DP - 2015 Mar 20 TI - Basket trials and the evolution of clinical trial design in an era of genomic medicine. PG - 975-7 LID - 10.1200/JCO.2014.59.8433 [doi] FAU - Redig, Amanda J AU - Redig AJ AD - Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. FAU - Janne, Pasi A AU - Janne PA AD - Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA pasi_janne@dfci.harvard.edu. LA - eng GR - T32 CA009172/CA/NCI NIH HHS/United States PT - Comment PT - Editorial DEP - 20150209 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Tumor Markers, Biological) SB - IM CON - J Clin Oncol. 2015 Mar 20;33(9):1000-7. PMID: 25667274 MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Small Cell Lung Carcinoma/*drug therapy MH - Thymus Neoplasms/*drug therapy MH - Tumor Markers, Biological/*metabolism EDAT- 2015/02/11 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/02/11 06:00 PHST- 2015/02/09 [aheadofprint] AID - JCO.2014.59.8433 [pii] AID - 10.1200/JCO.2014.59.8433 [doi] PST - ppublish SO - J Clin Oncol. 2015 Mar 20;33(9):975-7. doi: 10.1200/JCO.2014.59.8433. Epub 2015 Feb 9. PMID- 25667283 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150507 LR - 20150518 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 8 DP - 2015 Mar 10 TI - Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base. PG - 870-6 LID - 10.1200/JCO.2014.58.5380 [doi] AB - PURPOSE: To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. PATIENTS AND METHODS: Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (>/= 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. RESULTS: Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). CONCLUSION: For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. CI - (c) 2015 by American Society of Clinical Oncology. FAU - Robinson, Cliff G AU - Robinson CG AD - All authors: Washington University, St Louis, MO. crobinson@radonc.wustl.edu. FAU - Patel, Aalok P AU - Patel AP AD - All authors: Washington University, St Louis, MO. FAU - Bradley, Jeffrey D AU - Bradley JD AD - All authors: Washington University, St Louis, MO. FAU - DeWees, Todd AU - DeWees T AD - All authors: Washington University, St Louis, MO. FAU - Waqar, Saiama N AU - Waqar SN AD - All authors: Washington University, St Louis, MO. FAU - Morgensztern, Daniel AU - Morgensztern D AD - All authors: Washington University, St Louis, MO. FAU - Baggstrom, Maria Q AU - Baggstrom MQ AD - All authors: Washington University, St Louis, MO. FAU - Govindan, Ramaswamy AU - Govindan R AD - All authors: Washington University, St Louis, MO. FAU - Bell, Jennifer M AU - Bell JM AD - All authors: Washington University, St Louis, MO. FAU - Guthrie, Tracey J AU - Guthrie TJ AD - All authors: Washington University, St Louis, MO. FAU - Colditz, Graham A AU - Colditz GA AD - All authors: Washington University, St Louis, MO. FAU - Crabtree, Traves D AU - Crabtree TD AD - All authors: Washington University, St Louis, MO. FAU - Kreisel, Daniel AU - Kreisel D AD - All authors: Washington University, St Louis, MO. FAU - Krupnick, Alexander S AU - Krupnick AS AD - All authors: Washington University, St Louis, MO. FAU - Patterson, G Alexander AU - Patterson GA AD - All authors: Washington University, St Louis, MO. FAU - Meyers, Bryan F AU - Meyers BF AD - All authors: Washington University, St Louis, MO. FAU - Puri, Varun AU - Puri V AD - All authors: Washington University, St Louis, MO. LA - eng GR - K07CA178120/CA/NCI NIH HHS/United States GR - K12CA167540-02/CA/NCI NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150209 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*radiotherapy MH - Chemotherapy, Adjuvant/*methods MH - Databases, Factual MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/*radiotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Proportional Hazards Models MH - Regression Analysis MH - SEER Program MH - Treatment Outcome MH - United States MH - Urban Population PMC - PMC4348635 OID - NLM: PMC4348635 [Available on 03/10/16] EDAT- 2015/02/11 06:00 MHDA- 2015/05/08 06:00 CRDT- 2015/02/11 06:00 PMCR- 2016/03/10 00:00 PHST- 2015/02/09 [aheadofprint] AID - JCO.2014.58.5380 [pii] AID - 10.1200/JCO.2014.58.5380 [doi] PST - ppublish SO - J Clin Oncol. 2015 Mar 10;33(8):870-6. doi: 10.1200/JCO.2014.58.5380. Epub 2015 Feb 9. PMID- 25667277 OWN - NLM STAT- MEDLINE DA - 20150319 DCOM- 20150518 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 9 DP - 2015 Mar 20 TI - Validating ROS1 rearrangements as a therapeutic target in non-small-cell lung cancer. PG - 972-4 LID - 10.1200/JCO.2014.59.8334 [doi] FAU - Solomon, Benjamin AU - Solomon B AD - Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia ben.solomon@petermac.org. LA - eng PT - Comment PT - Editorial PT - Research Support, Non-U.S. Gov't DEP - 20150209 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 53AH36668S (crizotinib) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM CON - J Clin Oncol. 2015 Mar 20;33(9):992-9. PMID: 25667280 MH - Adenocarcinoma/*drug therapy/*genetics MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics MH - Female MH - *Gene Rearrangement MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics MH - Male MH - Protein-Tyrosine Kinases/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Pyrazoles/*therapeutic use MH - Pyridines/*therapeutic use EDAT- 2015/02/11 06:00 MHDA- 2015/05/20 06:00 CRDT- 2015/02/11 06:00 PHST- 2015/02/09 [aheadofprint] AID - JCO.2014.59.8334 [pii] AID - 10.1200/JCO.2014.59.8334 [doi] PST - ppublish SO - J Clin Oncol. 2015 Mar 20;33(9):972-4. doi: 10.1200/JCO.2014.59.8334. Epub 2015 Feb 9. PMID- 25628210 OWN - NLM STAT- MEDLINE DA - 20150128 DCOM- 20150511 IS - 2317-6385 (Electronic) IS - 1679-4508 (Linking) VI - 12 IP - 4 DP - 2014 Oct-Dec TI - Genetic polymorphisms and non-small-cell lung cancer: future paradigms. PG - 524-6 LID - 10.1590/S1679-45082014RB2906 [doi] LID - S1679-45082014000400524 [pii] AB - This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis. FAU - Mello, Ramon Andrade Bezerra de AU - Mello RA AD - Servico de Oncologia Medica, Instituto Portugues de Oncologia Francisco Gentil, Porto, Portugal. LA - eng LA - por PT - Journal Article PT - Review DEP - 20141118 PL - Brazil TA - Einstein (Sao Paulo) JT - Einstein (Sao Paulo, Brazil) JID - 101281800 RN - 0 (EML4-ALK fusion protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Tumor Markers, Biological) RN - 0 (Vascular Endothelial Growth Factor A) RN - 62229-50-9 (Epidermal Growth Factor) SB - IM MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Epidermal Growth Factor/genetics MH - Humans MH - Lung Neoplasms/*genetics MH - Oncogene Proteins, Fusion/genetics MH - Polymorphism, Genetic/*genetics MH - Tumor Markers, Biological/genetics MH - Vascular Endothelial Growth Factor A/genetics EDAT- 2015/01/30 06:00 MHDA- 2015/05/12 06:00 CRDT- 2015/01/29 06:00 PHST- 2013/07/07 [received] PHST- 2013/12/13 [accepted] PHST- 2014/11/18 [aheadofprint] AID - S1679-45082014000400524 [pii] AID - 10.1590/S1679-45082014RB2906 [doi] PST - ppublish SO - Einstein (Sao Paulo). 2014 Oct-Dec;12(4):524-6. doi: 10.1590/S1679-45082014RB2906. Epub 2014 Nov 18. PMID- 25625275 OWN - NLM STAT- MEDLINE DA - 20150304 DCOM- 20150430 IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 112 IP - 5 DP - 2015 Mar 3 TI - Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung. PG - 866-73 LID - 10.1038/bjc.2015.2 [doi] AB - BACKGROUND: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. MATERIAL AND METHODS: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). RESULTS: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). CONCLUSION: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung. FAU - Kayser, G AU - Kayser G AD - Department of Surgical Pathology, Institute of Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany. FAU - Csanadi, A AU - Csanadi A AD - Department of Surgical Pathology, Institute of Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany. FAU - Kakanou, S AU - Kakanou S AD - Department of Surgical Pathology, Institute of Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany. FAU - Prasse, A AU - Prasse A AD - Department of Pneumonology, University Medical Center Freiburg, Kilianstrasse 5, D-79106 Freiburg, Germany. FAU - Kassem, A AU - Kassem A AD - Department of Surgical Pathology, Institute of Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany. FAU - Stickeler, E AU - Stickeler E AD - Department of Gynecology and Obstetrics, University Medical Center Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. FAU - Passlick, B AU - Passlick B AD - Department of Thoracic Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. FAU - Zur Hausen, A AU - Zur Hausen A AD - Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 616, NL-6200 MD Maastricht, The Netherlands. LA - eng PT - Journal Article DEP - 20150127 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (MTSS1 protein, human) RN - 0 (Microfilament Proteins) RN - 0 (Neoplasm Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/metabolism/*pathology MH - Down-Regulation MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Lung Neoplasms/metabolism/*pathology MH - Male MH - Microfilament Proteins/*metabolism MH - Middle Aged MH - Neoplasm Proteins/*metabolism MH - Prognosis MH - Survival Analysis MH - Tissue Array Analysis EDAT- 2015/01/28 06:00 MHDA- 2015/05/01 06:00 CRDT- 2015/01/28 06:00 PHST- 2014/09/30 [received] PHST- 2014/12/22 [accepted] PHST- 2015/01/27 [aheadofprint] AID - bjc20152 [pii] AID - 10.1038/bjc.2015.2 [doi] PST - ppublish SO - Br J Cancer. 2015 Mar 3;112(5):866-73. doi: 10.1038/bjc.2015.2. Epub 2015 Jan 27. PMID- 25624439 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150507 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 8 DP - 2015 Mar 10 TI - Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. PG - 910-5 LID - 10.1200/JCO.2014.57.9334 [doi] AB - PURPOSE: Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials. PATIENTS AND METHODS: In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non-small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were "not at all," "a little," "quite a bit," and "very much." Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated. RESULTS: Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported "very much" toxicity, under-reporting by physicians ranged from 13.0% to 50.0%. CONCLUSION: Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials. CI - (c) 2015 by American Society of Clinical Oncology. FAU - Di Maio, Massimo AU - Di Maio M AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Gallo, Ciro AU - Gallo C AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Leighl, Natasha B AU - Leighl NB AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Piccirillo, Maria Carmela AU - Piccirillo MC AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Daniele, Gennaro AU - Daniele G AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Nuzzo, Francesco AU - Nuzzo F AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Gridelli, Cesare AU - Gridelli C AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Gebbia, Vittorio AU - Gebbia V AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Ciardiello, Fortunato AU - Ciardiello F AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - De Placido, Sabino AU - De Placido S AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Ceribelli, Anna AU - Ceribelli A AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Favaretto, Adolfo G AU - Favaretto AG AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - de Matteis, Andrea AU - de Matteis A AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Feld, Ronald AU - Feld R AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Butts, Charles AU - Butts C AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Bryce, Jane AU - Bryce J AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Signoriello, Simona AU - Signoriello S AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Morabito, Alessandro AU - Morabito A AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Rocco, Gaetano AU - Rocco G AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Perrone, Francesco AU - Perrone F AD - Massimo Di Maio, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Nuzzo, Andrea de Matteis, Jane Bryce, Alessandro Morabito, Gaetano Rocco, and Francesco Perrone, Istituto Nazionale Tumori-Fondazione "G. Pascale" Istituto di Ricovero e Cura a Carattere Scientifico; Ciro Gallo, Fortunato Ciardiello, and Simona Signoriello, Second University; Sabino De Placido, Federico II University, Napoli; Cesare Gridelli, S.G. Moscati Hospital, Avellino; Vittorio Gebbia, Istituto La Maddalena, Palermo; Anna Ceribelli, Regina Elena National Cancer Institute, Roma; Adolfo G. Favaretto, Istituto Oncologico Veneto, Padova, Italy; Natasha B. Leighl and Ronald Feld, Princess Margaret Hospital/University Health Network, Toronto; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada. f.perrone@istitutotumori.na.it. LA - eng SI - ClinicalTrials.gov/NCT00331097 SI - ClinicalTrials.gov/NCT00349219 SI - ClinicalTrials.gov/NCT00385606 PT - Journal Article PT - Randomized Controlled Trial DEP - 20150126 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antineoplastic Agents) SB - IM CIN - BMJ. 2015;350:h485. PMID: 25630342 CIN - Lancet Oncol. 2015 Mar;16(3):e107. PMID: 25639368 MH - Adult MH - Aged MH - Aged, 80 and over MH - Anorexia/chemically induced MH - Antineoplastic Agents/*adverse effects MH - Breast Neoplasms/*drug therapy MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Chemotherapy, Adjuvant/*adverse effects MH - Constipation/chemically induced MH - Diarrhea/chemically induced MH - Europe MH - Female MH - Humans MH - Hypotrichosis/chemically induced MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Nausea/chemically induced MH - Patient Participation MH - Physicians MH - Prospective Studies MH - Quality of Life MH - Questionnaires MH - Reproducibility of Results MH - Treatment Outcome MH - Vomiting/chemically induced EDAT- 2015/01/28 06:00 MHDA- 2015/05/08 06:00 CRDT- 2015/01/28 06:00 PHST- 2015/01/26 [aheadofprint] AID - JCO.2014.57.9334 [pii] AID - 10.1200/JCO.2014.57.9334 [doi] PST - ppublish SO - J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26. PMID- 25624438 OWN - NLM STAT- MEDLINE DA - 20150309 DCOM- 20150507 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 8 DP - 2015 Mar 10 TI - Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. PG - 861-9 LID - 10.1200/JCO.2014.56.6661 [doi] AB - PURPOSE: A nomogram is a useful and convenient tool for individualized cancer prognoses. We sought to develop a clinical nomogram for predicting survival of patients with resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: On the basis of data from a multi-institutional registry of 6,111 patients with resected NSCLC in China, we identified and integrated significant prognostic factors for survival to build a nomogram. The model was subjected to bootstrap internal validation and to external validation with a separate cohort of 2,148 patients from the International Association for the Study of Lung Cancer (IASLC) database. The predictive accuracy and discriminative ability were measured by concordance index (C-index) and risk group stratification. RESULTS: A total of 5,261 patients were included for analysis. Six independent prognostic factors were identified and entered into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year overall survival (OS) showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of the seventh edition American Joint Committee on Cancer TNM staging system for predicting OS (primary cohort, 0.71 v 0.68, respectively; P < .01; IASLC cohort, 0.67 v 0.64, respectively; P = .06). The stratification into different risk groups allowed significant distinction between survival curves within respective TNM categories. CONCLUSION: We established and validated a novel nomogram that can provide individual prediction of OS for patients with resected NSCLC. This practical prognostic model may help clinicians in decision making and design of clinical studies. CI - (c) 2015 by American Society of Clinical Oncology. FAU - Liang, Wenhua AU - Liang W AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Zhang, Li AU - Zhang L AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Jiang, Gening AU - Jiang G AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Wang, Qun AU - Wang Q AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Liu, Lunxu AU - Liu L AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Liu, Deruo AU - Liu D AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Wang, Zheng AU - Wang Z AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Zhu, Zhihua AU - Zhu Z AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Deng, Qiuhua AU - Deng Q AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Xiong, Xinguo AU - Xiong X AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Shao, Wenlong AU - Shao W AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - Shi, Xiaoshun AU - Shi X AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. FAU - He, Jianxing AU - He J AD - Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, The First Affiliated Hospital of Guangzhou Medical University; Wenhua Liang, Qiuhua Deng, Xinguo Xiong, Wenlong Shao, Xiaoshun Shi, and Jianxing He, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease; Wenhua Liang, Li Zhang, and Zhihua Zhu, Cancer Center of Sun Yat-Sen University, Guangzhou; Gening Jiang, Shanghai Pulmonary Hospital of Tongji University; Qun Wang, Shanghai Zhongshan Hospital of Fudan University, Shanghai; Lunxu Liu, West China Hospital, Sichuan University, Chengdu; Deruo Liu, China and Japan Friendship Hospital, Beijing; and Zheng Wang, Shenzhen People's Hospital, Shenzhen, People's Republic of China. drjianxing.he@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PT - Validation Studies DEP - 20150126 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 SB - IM MH - Aged MH - Algorithms MH - Calibration MH - Carcinoma, Non-Small-Cell Lung/*mortality/*surgery MH - China MH - Decision Making MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*mortality/*surgery MH - Male MH - Middle Aged MH - *Nomograms MH - Outcome Assessment (Health Care) MH - Prognosis MH - Registries MH - Reproducibility of Results MH - Treatment Outcome EDAT- 2015/01/28 06:00 MHDA- 2015/05/08 06:00 CRDT- 2015/01/28 06:00 PHST- 2015/01/26 [aheadofprint] AID - JCO.2014.56.6661 [pii] AID - 10.1200/JCO.2014.56.6661 [doi] PST - ppublish SO - J Clin Oncol. 2015 Mar 10;33(8):861-9. doi: 10.1200/JCO.2014.56.6661. Epub 2015 Jan 26. PMID- 25605928 OWN - NLM STAT- MEDLINE DA - 20150204 DCOM- 20150428 LR - 20150213 IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 112 IP - 5 DP - 2015 Feb 3 TI - Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer. PG - 1547-52 LID - 10.1073/pnas.1424024112 [doi] AB - Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non-small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment-while reducing blood flow, volume, and permeability in the overall population-may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. FAU - Heist, Rebecca S AU - Heist RS AD - Departments of Medicine, rheist@partners.org jain@steele.mgh.harvard.edu. FAU - Duda, Dan G AU - Duda DG AD - Radiation Oncology, and. FAU - Sahani, Dushyant V AU - Sahani DV AD - Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; FAU - Ancukiewicz, Marek AU - Ancukiewicz M AD - Radiation Oncology, and. FAU - Fidias, Panos AU - Fidias P AD - Department of Medical Oncology, University of Arizona Cancer Center at Dignity, Phoenix, AZ 85013; FAU - Sequist, Lecia V AU - Sequist LV AD - Departments of Medicine. FAU - Temel, Jennifer S AU - Temel JS AD - Departments of Medicine. FAU - Shaw, Alice T AU - Shaw AT AD - Departments of Medicine. FAU - Pennell, Nathan A AU - Pennell NA AD - Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH 44195; FAU - Neal, Joel W AU - Neal JW AD - Department of Medicine, Division of Oncology, Stanford University/Stanford Cancer Institute, Palo Alto, CA 94305; FAU - Gandhi, Leena AU - Gandhi L AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and. FAU - Lynch, Thomas J AU - Lynch TJ AD - Department of Medical Oncology, Yale Cancer Center, New Haven, CT 06520. FAU - Engelman, Jeffrey A AU - Engelman JA AD - Departments of Medicine. FAU - Jain, Rakesh K AU - Jain RK AD - Radiation Oncology, and rheist@partners.org jain@steele.mgh.harvard.edu. LA - eng GR - P01CA080124/CA/NCI NIH HHS/United States GR - R01CA159258/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150120 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (130-nm albumin-bound paclitaxel) RN - 0 (Albumins) RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Tumor Markers, Biological) RN - 0 (Vascular Endothelial Growth Factor A) RN - 2S9ZZM9Q9V (bevacizumab) RN - 33069-62-4 (Paclitaxel) RN - BG3F62OND5 (Carboplatin) SB - IM MH - Albumins/administration & dosage MH - Angiogenesis Inhibitors/*therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/blood supply/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/blood supply/*drug therapy MH - Male MH - Middle Aged MH - Neovascularization, Pathologic/*drug therapy MH - Paclitaxel/administration & dosage MH - Tumor Markers, Biological/blood MH - Vascular Endothelial Growth Factor A/*antagonists & inhibitors PMC - PMC4321320 OID - NLM: PMC4321320 OTO - NOTNLM OT - antiangiogenesis OT - bioimaging OT - lung cancer EDAT- 2015/01/22 06:00 MHDA- 2015/04/29 06:00 CRDT- 2015/01/22 06:00 PHST- 2015/01/20 [aheadofprint] AID - 1424024112 [pii] AID - 10.1073/pnas.1424024112 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1547-52. doi: 10.1073/pnas.1424024112. Epub 2015 Jan 20. PMID- 25576649 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150521 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 98 IP - 1 DP - 2015 Feb TI - Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study. PG - 113-8 LID - 10.1016/j.yexmp.2015.01.005 [doi] LID - S0014-4800(15)00007-6 [pii] AB - In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identifying ALK rearrangements in patients. FISH is often considered a labor and cost intensive molecular technique, and in this study we aimed to demonstrate feasibility for automation of ALK FISH testing, to improve laboratory workflow and ease of testing. This involved automation of the pre-treatment steps of the ALK assay using various protocols on the VP 2000 instrument, and facilitating automated scanning of the fluorescent FISH specimens for simplified enumeration on various backend scanning and analysis systems. The results indicated that ALK FISH can be automated. Significantly, both the Ikoniscope and BioView system of automated FISH scanning and analysis systems provided a robust analysis algorithm to define ALK rearrangements. In addition, the BioView system facilitated consultation of difficult cases via the internet. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Zwaenepoel, Karen AU - Zwaenepoel K AD - Antwerp University Hospital, Department of Pathology, Wilrijkstraat 10, 2650 Edegem, Belgium. Electronic address: Karen.Zwaenepoel@uza.be. FAU - Merkle, Dennis AU - Merkle D AD - Abbott Molecular, Max-Planck-Ring 2, 65205 Wiesbaden, Germany. FAU - Cabillic, Florian AU - Cabillic F AD - University of Rennes 1, Faculty of Medicine, Service de Cytogenetique et Biologie Cellulaire, CHU de Rennes, rue Henri Le Guilloux, 35033 Rennes CEDEX 9, France. FAU - Berg, Erica AU - Berg E AD - Charite University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. FAU - Belaud-Rotureau, Marc-Antoine AU - Belaud-Rotureau MA AD - University of Rennes 1, Faculty of Medicine, Service de Cytogenetique et Biologie Cellulaire, CHU de Rennes, rue Henri Le Guilloux, 35033 Rennes CEDEX 9, France. FAU - Grazioli, Vittorio AU - Grazioli V AD - Italian Center of Diagnostics, Laboratory of Molecular Biology and Genetics, Via Saint Bon 20, 20147 Milan, Italy. FAU - Herelle, Olga AU - Herelle O AD - Abbott Molecular, Rue de la Couture 12, 94518 Rungis, France. FAU - Hummel, Michael AU - Hummel M AD - Charite University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. FAU - Le Calve, Michele AU - Le Calve M AD - University of Rennes 1, Faculty of Medicine, Service de Cytogenetique et Biologie Cellulaire, CHU de Rennes, rue Henri Le Guilloux, 35033 Rennes CEDEX 9, France. FAU - Lenze, Dido AU - Lenze D AD - Charite University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. FAU - Mende, Stefanie AU - Mende S AD - Charite University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. FAU - Pauwels, Patrick AU - Pauwels P AD - Antwerp University Hospital, Department of Pathology, Wilrijkstraat 10, 2650 Edegem, Belgium. FAU - Quilichini, Benoit AU - Quilichini B AD - Biomnis Laboratory, Laboratory of Cytogenetics, 17-19 av Tony Garnier, 69357 Lyon, France. FAU - Repetti, Elena AU - Repetti E AD - Italian Center of Diagnostics, Laboratory of Molecular Biology and Genetics, Via Saint Bon 20, 20147 Milan, Italy. LA - eng PT - Journal Article DEP - 20150108 PL - United States TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 53AH36668S (crizotinib) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (anaplastic lymphoma kinase) SB - IM MH - Algorithms MH - Automation MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/pathology MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - *Data Interpretation, Statistical MH - Feasibility Studies MH - *Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Lung Neoplasms/drug therapy/*genetics/pathology MH - Neoplasm Staging MH - Prognosis MH - Protein Kinase Inhibitors/therapeutic use MH - Pyrazoles/therapeutic use MH - Pyridines/therapeutic use MH - Receptor Protein-Tyrosine Kinases/*genetics MH - Software OTO - NOTNLM OT - ALK OT - Automation OT - BioView OT - FISH OT - Fluorescence in situ hybridization OT - VP 2000 EDAT- 2015/01/13 06:00 MHDA- 2015/05/23 06:00 CRDT- 2015/01/11 06:00 PHST- 2014/12/24 [received] PHST- 2015/01/06 [accepted] PHST- 2015/01/08 [aheadofprint] AID - S0014-4800(15)00007-6 [pii] AID - 10.1016/j.yexmp.2015.01.005 [doi] PST - ppublish SO - Exp Mol Pathol. 2015 Feb;98(1):113-8. doi: 10.1016/j.yexmp.2015.01.005. Epub 2015 Jan 8. PMID- 25560531 OWN - NLM STAT- MEDLINE DA - 20150129 DCOM- 20150521 IS - 1759-4782 (Electronic) IS - 1759-4774 (Linking) VI - 12 IP - 2 DP - 2015 Feb TI - Targeted therapies: new standard for ALK-positive NSCLC. PG - 66 LID - 10.1038/nrclinonc.2014.235 [doi] FAU - Hutchinson, Lisa AU - Hutchinson L LA - eng PT - Comment PT - Journal Article DEP - 20150106 PL - England TA - Nat Rev Clin Oncol JT - Nature reviews. Clinical oncology JID - 101500077 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM CON - N Engl J Med. 2014 Dec 4;371(23):2167-77. PMID: 25470694 MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Protein Kinase Inhibitors/*therapeutic use MH - Pyrazoles/*therapeutic use MH - Pyridines/*therapeutic use MH - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors EDAT- 2015/01/07 06:00 MHDA- 2015/05/23 06:00 CRDT- 2015/01/07 06:00 PHST- 2015/01/06 [aheadofprint] AID - nrclinonc.2014.235 [pii] AID - 10.1038/nrclinonc.2014.235 [doi] PST - ppublish SO - Nat Rev Clin Oncol. 2015 Feb;12(2):66. doi: 10.1038/nrclinonc.2014.235. Epub 2015 Jan 6. PMID- 25509698 OWN - NLM STAT- MEDLINE DA - 20141215 DCOM- 20150511 IS - 0125-2208 (Print) IS - 0125-2208 (Linking) VI - 97 Suppl 11 DP - 2014 Nov TI - Quality of life in advanced non-small cell lung cancer receiving chemotherapy of platinum combination in old versus new standard chemotherapy regimen. PG - S69-75 AB - BACKGROUND AND OBJECTIVE: Non-small cell lung cancers (NSCLC) mostly are adenocarcinoma but minor squamous cell carcinoma is related to smoking. Surgery has a major role in early stage with chemotherapy or radiation in advanced stage. Platinum combination chemotherapy could increase the progression free survival which may be combined with etoposide as the old standard regimen or paclitaxel/gemcitabine as the new standard regimen with slightly more benefit. This study was conducted to evaluate quality of life (QoL) and response of chemotherapy. MATERIAL AND METHOD: The prospective study in advanced NSCLC enrolled 88 patients receiving chemotherapy with old or new standard regimen in the Oncology Unit, Medicine Department of Rajavithi Hospital from January 2004 to December 2009. The assessments were composed of the result of treatment and QoL evaluated by Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L) in both groups. RESULTS: The 88 advanced NSCLC patients received old standard chemotherapy 49 cases and new standard chemotherapy 39 cases. No statistically significant difference was found in baseline characteristics and most had adenocarcinoma subtype. The overall QoL scores before and after treatment were similar except a slight decrease in social/family well-being. The overall response rate was increased in the new standard regimen group compared with the old regimen group (61.5% versus 24.5%) but without statistical difference in median progression free survival (23 and 20 weeks, respectively). CONCLUSION: New standard chemotherapy regimen demonstrated increased overall response rate and without decreased QoL. FAU - Maneechawakajorn, Jedzada AU - Maneechawakajorn J FAU - Suksuperm, Jeerajed AU - Suksuperm J LA - eng PT - Journal Article PL - Thailand TA - J Med Assoc Thai JT - Journal of the Medical Association of Thailand = Chotmaihet thangphaet JID - 7507216 RN - 0 (Antineoplastic Agents) RN - 0 (Organoplatinum Compounds) RN - 0W860991D6 (Deoxycytidine) RN - 33069-62-4 (Paclitaxel) RN - 6PLQ3CP4P3 (Etoposide) RN - B76N6SBZ8R (gemcitabine) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology/*psychology MH - Cohort Studies MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Disease-Free Survival MH - Etoposide/administration & dosage MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology/*psychology MH - Male MH - Middle Aged MH - Organoplatinum Compounds/administration & dosage MH - Paclitaxel/administration & dosage MH - Prospective Studies MH - Quality of Life EDAT- 2014/12/17 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/12/17 06:00 PST - ppublish SO - J Med Assoc Thai. 2014 Nov;97 Suppl 11:S69-75. PMID- 25490255 OWN - NLM STAT- MEDLINE DA - 20150120 DCOM- 20150430 IS - 1748-880X (Electronic) IS - 0007-1285 (Linking) VI - 88 IP - 1046 DP - 2015 Feb TI - Patients with severe emphysema have a low risk of radiation pneumonitis following stereotactic body radiotherapy. PG - 20140596 LID - 10.1259/bjr.20140596 [doi] AB - OBJECTIVE: To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema. METHODS: This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75 Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49-90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard's criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT. RESULTS: On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p = 0.01), mild emphysema (p = 0.04) and no underlying lung disease (p = 0.01). CONCLUSION: Patients with severe emphysema had a low risk of RP following SBRT. ADVANCES IN KNOWLEDGE: Little is known about the association between RP and pulmonary emphysema. Patients with severe emphysema had lower risk of RP than those with no underlying lung disease. FAU - Ishijima, M AU - Ishijima M AD - Department of Radiology, Tokyo Medical University Hospital, Tokyo, Japan. FAU - Nakayama, H AU - Nakayama H FAU - Itonaga, T AU - Itonaga T FAU - Tajima, Y AU - Tajima Y FAU - Shiraishi, S AU - Shiraishi S FAU - Okubo, M AU - Okubo M FAU - Mikami, R AU - Mikami R FAU - Tokuuye, K AU - Tokuuye K LA - eng PT - Journal Article DEP - 20141209 PL - England TA - Br J Radiol JT - The British journal of radiology JID - 0373125 SB - AIM SB - IM MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*surgery MH - Female MH - Follow-Up Studies MH - Humans MH - Incidence MH - Japan/epidemiology MH - Lung Neoplasms/diagnosis/*surgery MH - Male MH - Middle Aged MH - Pulmonary Emphysema/*diagnosis/etiology MH - Radiation Pneumonitis/*complications/diagnosis/epidemiology MH - Radiosurgery/*methods MH - Retrospective Studies MH - Risk Factors MH - Tomography, X-Ray Computed EDAT- 2014/12/10 06:00 MHDA- 2015/05/01 06:00 CRDT- 2014/12/10 06:00 PHST- 2014/12/09 [aheadofprint] AID - 10.1259/bjr.20140596 [doi] PST - ppublish SO - Br J Radiol. 2015 Feb;88(1046):20140596. doi: 10.1259/bjr.20140596. Epub 2014 Dec 9. PMID- 25451483 OWN - NLM STAT- MEDLINE DA - 20150302 DCOM- 20150427 IS - 1097-685X (Electronic) IS - 0022-5223 (Linking) VI - 149 IP - 2 DP - 2015 Feb TI - Pulmonary rehabilitation during induction chemoradiotherapy for lung cancer improves pulmonary function. PG - 569-73 LID - 10.1016/j.jtcvs.2014.09.123 [doi] LID - S0022-5223(14)01398-1 [pii] AB - OBJECTIVE: Chemoradiotherapy for non-small cell lung cancer can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with non-small cell lung cancer who underwent induction chemoradiotherapy. METHODS: A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes. RESULTS: All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (+6.4%, P = .0096) and forced expiratory volume in 1 second (+10.4%, P < .0001). Diffusing capacity of the lung for carbon monoxide decreased (-14.0%, P < .0001). Patients with respiratory impairment (forced vital capacity <80% predicted or forced expiratory volume in 1 second/forced vital capacity <70%) showed significant improvements in forced vital capacity (+13.9%, P = .0025) and forced expiratory volume in 1 second (+22.5%, P < .0001). Significant increases were observed in forced vital capacity (+7.0%, P = .0042) and forced expiratory volume in 1 second (+10.8%, P = .0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%. CONCLUSIONS: A pulmonary rehabilitation program for patients with non-small cell lung cancer undergoing induction chemoradiotherapy seems to improve respiratory function. It is particularly recommended for smokers and patients with respiratory impairment. CI - Copyright (c) 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved. FAU - Tarumi, Shintaro AU - Tarumi S AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. Electronic address: starumi@med.kagawa-u.ac.jp. FAU - Yokomise, Hiroyasu AU - Yokomise H AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. FAU - Gotoh, Masashi AU - Gotoh M AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. FAU - Kasai, Yoshitaka AU - Kasai Y AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. FAU - Matsuura, Natsumi AU - Matsuura N AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. FAU - Chang, Sung Soo AU - Chang SS AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. FAU - Go, Tetsuhiko AU - Go T AD - Faculty of Medicine, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Kagawa University, Kagawa, Japan. LA - eng PT - Journal Article DEP - 20141005 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 SB - AIM SB - IM CIN - J Thorac Cardiovasc Surg. 2015 Feb;149(2):574-5. PMID: 25726880 MH - Adult MH - Aged MH - Carcinoma, Non-Small-Cell Lung/mortality/*physiopathology/surgery/*therapy MH - *Chemoradiotherapy MH - Combined Modality Therapy MH - Female MH - Humans MH - Lung Neoplasms/mortality/*physiopathology/surgery/*therapy MH - Male MH - Middle Aged MH - Pneumonectomy MH - Postoperative Complications/mortality MH - Respiratory Function Tests MH - Retrospective Studies EDAT- 2014/12/03 06:00 MHDA- 2015/04/29 06:00 CRDT- 2014/12/03 06:00 PHST- 2013/10/18 [received] PHST- 2014/09/04 [revised] PHST- 2014/09/27 [accepted] PHST- 2014/10/05 [aheadofprint] AID - S0022-5223(14)01398-1 [pii] AID - 10.1016/j.jtcvs.2014.09.123 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2015 Feb;149(2):569-73. doi: 10.1016/j.jtcvs.2014.09.123. Epub 2014 Oct 5. PMID- 25449594 OWN - NLM STAT- MEDLINE DA - 20150129 DCOM- 20150512 LR - 20150507 IS - 2210-3244 (Electronic) IS - 1672-0229 (Linking) VI - 12 IP - 5 DP - 2014 Oct TI - Pharmacogenomics of cisplatin sensitivity in non-small cell lung cancer. PG - 198-209 LID - 10.1016/j.gpb.2014.10.003 [doi] LID - S1672-0229(14)00109-0 [pii] AB - Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC) as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomarkers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers. CI - Copyright (c) 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved. FAU - Rose, Maimon C AU - Rose MC AD - Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA. FAU - Kostyanovskaya, Elina AU - Kostyanovskaya E AD - Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA. FAU - Huang, R Stephanie AU - Huang RS AD - Department of Medicine, University of Chicago, Chicago, IL 60637, USA. Electronic address: rhuang@medicine.bsd.uchicago.edu. LA - eng GR - CA125183/CA/NCI NIH HHS/United States GR - K08GM089941/GM/NIGMS NIH HHS/United States GR - P30 CA14599/CA/NCI NIH HHS/United States GR - R21 CA139278/CA/NCI NIH HHS/United States GR - U01GM61393/GM/NIGMS NIH HHS/United States GR - UL1RR024999/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20141028 PL - China TA - Genomics Proteomics Bioinformatics JT - Genomics, proteomics & bioinformatics JID - 101197608 RN - 0 (Antineoplastic Agents) RN - 0 (Tumor Markers, Biological) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antineoplastic Agents/pharmacology MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics MH - Cisplatin/*pharmacology MH - Drug Resistance, Neoplasm/*genetics MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics MH - *Pharmacogenetics MH - Tumor Markers, Biological/*genetics PMC - PMC4411417 OID - NLM: PMC4411417 OTO - NOTNLM OT - Biomarker OT - Cisplatin OT - Copper transport OT - Glutathione S-transferase OT - Non-small cell lung cancer OT - Nucleotide excision repair EDAT- 2014/12/03 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/09/18 [received] PHST- 2014/10/11 [revised] PHST- 2014/10/13 [accepted] PHST- 2014/10/28 [aheadofprint] AID - S1672-0229(14)00109-0 [pii] AID - 10.1016/j.gpb.2014.10.003 [doi] PST - ppublish SO - Genomics Proteomics Bioinformatics. 2014 Oct;12(5):198-209. doi: 10.1016/j.gpb.2014.10.003. Epub 2014 Oct 28. PMID- 25449334 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150521 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 98 IP - 1 DP - 2015 Feb TI - Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma. PG - 27-32 LID - 10.1016/j.yexmp.2014.11.010 [doi] LID - S0014-4800(14)00185-3 [pii] AB - Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAC. LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Stojsic, Jelena AU - Stojsic J AD - Department of Thoracopulmonary Pathology Service of Pathology, Clinical Centre of Serbia, Koste Todorovica 20/26, 11000 Belgrade, Serbia. FAU - Stankovic, Tijana AU - Stankovic T AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Stojkovic, Sonja AU - Stojkovic S AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Milinkovic, Vedrana AU - Milinkovic V AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Dinic, Jelena AU - Dinic J AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Milosevic, Zorica AU - Milosevic Z AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Milovanovic, Zorka AU - Milovanovic Z AD - Institute for Oncology and Radiology of Serbia, University of Belgrade, Pasterova 14, 11000 Belgrade, Serbia. FAU - Tanic, Nikola AU - Tanic N AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. FAU - Bankovic, Jasna AU - Bankovic J AD - Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: jasnam@ibiss.bg.ac.rs. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141120 PL - United States TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Tumor Markers, Biological) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.48 (PTEN protein, human) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM MH - Adenocarcinoma/drug therapy/metabolism/*mortality/pathology MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism/*mortality/pathology MH - Carcinoma, Squamous Cell/drug therapy/metabolism/*mortality/pathology MH - Female MH - Follow-Up Studies MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunoenzyme Techniques MH - Loss of Heterozygosity MH - Lung Neoplasms/drug therapy/metabolism/*mortality/pathology MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy MH - Neoplasm Grading MH - Neoplasm Invasiveness MH - Neoplasm Staging MH - PTEN Phosphohydrolase/genetics MH - Phosphatidylinositol 3-Kinases/metabolism MH - Polymerase Chain Reaction MH - Prognosis MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction MH - Survival Rate MH - TOR Serine-Threonine Kinases/metabolism MH - Tumor Markers, Biological/*metabolism OTO - NOTNLM OT - Neodjuvant chemotherapy OT - Non-small cell lung carcinoma OT - PTEN OT - pAKT OT - pERK EDAT- 2014/12/03 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/11/13 [received] PHST- 2014/11/18 [accepted] PHST- 2014/11/20 [aheadofprint] AID - S0014-4800(14)00185-3 [pii] AID - 10.1016/j.yexmp.2014.11.010 [doi] PST - ppublish SO - Exp Mol Pathol. 2015 Feb;98(1):27-32. doi: 10.1016/j.yexmp.2014.11.010. Epub 2014 Nov 20. PMID- 25377507 OWN - NLM STAT- MEDLINE DA - 20150305 DCOM- 20150508 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 121 IP - 6 DP - 2015 Mar 15 TI - Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non-small cell lung cancer. PG - 883-92 LID - 10.1002/cncr.29132 [doi] AB - BACKGROUND: Vascular endothelial growth factor (VEGF)-mediated angiogenesis plays an important role in non-small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC. METHODS: Eligible stage IV nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were randomized 1:1 to pemetrexed and carboplatin (or cisplatin) or ramucirumab (10 mg/kg) plus pemetrexed and carboplatin (or cisplatin) once every 3 weeks. Treatment was given for 4 to 6 cycles, and this was followed by a maintenance phase with pemetrexed or ramucirumab and pemetrexed. The primary endpoint was progression-free survival (PFS) with a sample size of sufficient power to detect an increase from 7 to 10.4 months. RESULTS: From October 2010 to October 2011, 140 patients were randomized (pemetrexed-platinum arm, 71; ramucirumab-pemetrexed-platinum arm, 69), and most baseline characteristics were similar for the 2 treatment arms. The median PFS was 5.6 months for the pemetrexed-platinum arm and 7.2 months for the ramucirumab-pemetrexed-platinum arm (hazard ratio, 0.75; P = .132). The objective response rates were 38.0% and 49.3% for the pemetrexed-platinum and ramucirumab-pemetrexed-platinum arms, respectively (P = .180). The disease control rate was 70.4% for the pemetrexed-platinum arm and 85.5% for the ramucirumab-pemetrexed-platinum arm (P = .032). The grade 3 or higher adverse events occurring in 10% or more of patients were thrombocytopenia, neutropenia, fatigue, anemia, nausea, back pain, and hypertension. CONCLUSIONS: The primary endpoint of significant prolongation of PFS was not met; however, ramucirumab showed evidence of clinical activity in combination with pemetrexed and platinum in nonsquamous NSCLC patients. The addition of ramucirumab to pemetrexed and platinum did not result in new or unexpected safety findings. CI - (c) 2014 American Cancer Society. FAU - Doebele, Robert C AU - Doebele RC AD - University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Spigel, David AU - Spigel D FAU - Tehfe, Mustapha AU - Tehfe M FAU - Thomas, Sachdev AU - Thomas S FAU - Reck, Martin AU - Reck M FAU - Verma, Sunil AU - Verma S FAU - Eakle, Janice AU - Eakle J FAU - Bustin, Frederique AU - Bustin F FAU - Goldschmidt, Jerome Jr AU - Goldschmidt J Jr FAU - Cao, Dachuang AU - Cao D FAU - Alexandris, Ekaterine AU - Alexandris E FAU - Yurasov, Sergey AU - Yurasov S FAU - Camidge, D Ross AU - Camidge DR FAU - Bonomi, Philip AU - Bonomi P LA - eng SI - ClinicalTrials.gov/NCT01160744 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141106 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal) RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - BG3F62OND5 (Carboplatin) RN - D99YVK4L0X (ramucirumab) RN - Q20Q21Q62J (Cisplatin) SB - AIM SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antibodies, Monoclonal/administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Cisplatin/administration & dosage/adverse effects MH - Disease-Free Survival MH - Female MH - Glutamates/administration & dosage/adverse effects MH - Guanine/administration & dosage/adverse effects/analogs & derivatives MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Young Adult OTO - NOTNLM OT - non-small cell lung cancer (NSCLC) OT - nonsquamous OT - pemetrexed OT - platinum OT - ramucirumab OT - vascular endothelial growth factor (VEGF) EDAT- 2014/11/08 06:00 MHDA- 2015/05/09 06:00 CRDT- 2014/11/08 06:00 PHST- 2014/07/02 [received] PHST- 2014/10/03 [revised] PHST- 2014/10/09 [accepted] PHST- 2014/11/06 [aheadofprint] AID - 10.1002/cncr.29132 [doi] PST - ppublish SO - Cancer. 2015 Mar 15;121(6):883-92. doi: 10.1002/cncr.29132. Epub 2014 Nov 6. PMID- 25355643 OWN - NLM STAT- MEDLINE DA - 20141030 DCOM- 20150501 IS - 1863-6713 (Electronic) IS - 1863-6705 (Linking) VI - 62 IP - 11 DP - 2014 Nov TI - Current status of induction treatment for N2-Stage III non-small cell lung cancer. PG - 651-9 LID - 10.1007/s11748-014-0447-1 [doi] AB - Locally advanced non-small cell lung cancer (NSCLC), particularly clinical Stage IIIA NSCLC with mediastinal lymph node metastasis, is known to be quite heterogeneous, comprising approximately one-fourth of cases of NSCLC. In this subset, patients with a minor tumor load in the mediastinal lymph nodes, such as microscopically or pathologically proven N2 in the resected specimens, are treated with surgery followed by adjuvant chemotherapy. Meanwhile, the current standard of care for patients with bulky or infiltrative N2 disease is concurrent chemoradiotherapy. The potential role of surgery in multi-modality treatment for clinical N2-Stage IIIA remains controversial. Several prospective clinical trials of this subset have been conducted; however, the heterogeneity of the N2 status and differences in chemotherapy regimens and/or radiation modalities between clinical trials make the results difficult to compare. No optimal chemotherapy regimen has been established to control possible micrometastasis, and radiotherapy is often used to achieve maximum local disease control and minimize post-surgical complications. This review summarizes the findings of prospective clinical trials that assessed the role of surgery in treating clinical N2-Stage IIIA patients within the last two decades and discusses the present status of induction treatment followed by surgery for clinical N2-Stage IIIA NSCLC. FAU - Yamaguchi, Masafumi AU - Yamaguchi M AD - Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan. FAU - Sugio, Kenji AU - Sugio K LA - eng PT - Journal Article PT - Review DEP - 20140718 PL - Japan TA - Gen Thorac Cardiovasc Surg JT - General thoracic and cardiovascular surgery JID - 101303952 SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/pathology/secondary/*therapy MH - Chemoradiotherapy MH - Chemotherapy, Adjuvant MH - Clinical Trials, Phase III as Topic MH - Combined Modality Therapy MH - Humans MH - Induction Chemotherapy/*methods MH - Lung Neoplasms/pathology/*therapy MH - Lymphatic Metastasis MH - Neoplasm Staging MH - Pneumonectomy MH - Prospective Studies MH - Tumor Burden EDAT- 2014/10/31 06:00 MHDA- 2015/05/02 06:00 CRDT- 2014/10/31 06:00 PHST- 2014/05/08 [received] PHST- 2014/07/18 [aheadofprint] AID - 10.1007/s11748-014-0447-1 [doi] PST - ppublish SO - Gen Thorac Cardiovasc Surg. 2014 Nov;62(11):651-9. doi: 10.1007/s11748-014-0447-1. Epub 2014 Jul 18. PMID- 25348786 OWN - NLM STAT- MEDLINE DA - 20141124 DCOM- 20150520 IS - 1759-4782 (Electronic) IS - 1759-4774 (Linking) VI - 11 IP - 12 DP - 2014 Dec TI - Lung cancer: Heterogeneity in space and time. PG - 684 LID - 10.1038/nrclinonc.2014.186 [doi] FAU - Errico, Alessia AU - Errico A LA - eng PT - Comment PT - Journal Article DEP - 20141028 PL - England TA - Nat Rev Clin Oncol JT - Nature reviews. Clinical oncology JID - 101500077 SB - IM CON - Science. 2014 Oct 10;346(6206):256-9. PMID: 25301631 CON - Science. 2014 Oct 10;346(6206):251-6. PMID: 25301630 MH - Adenocarcinoma/*genetics MH - Carcinoma, Non-Small-Cell Lung/*diagnosis/*genetics MH - *Genetic Heterogeneity MH - *Genomic Instability MH - Humans MH - Lung Neoplasms/*diagnosis/*genetics MH - Neoplasm Recurrence, Local/*genetics EDAT- 2014/10/29 06:00 MHDA- 2015/05/21 06:00 CRDT- 2014/10/29 06:00 PHST- 2014/10/28 [aheadofprint] AID - nrclinonc.2014.186 [pii] AID - 10.1038/nrclinonc.2014.186 [doi] PST - ppublish SO - Nat Rev Clin Oncol. 2014 Dec;11(12):684. doi: 10.1038/nrclinonc.2014.186. Epub 2014 Oct 28. PMID- 25344291 OWN - NLM STAT- MEDLINE DA - 20150317 DCOM- 20150519 IS - 1617-4623 (Electronic) IS - 1617-4623 (Linking) VI - 290 IP - 2 DP - 2015 Apr TI - Common genetic variants on 3q28 contribute to non-small cell lung cancer susceptibility: evidence from 10 case-control studies. PG - 573-84 LID - 10.1007/s00438-014-0934-1 [doi] AB - The association between common variations (rs10937405, rs4488809) on 3q28 and lung cancer has been widely evaluated in various ethnic groups, since it was first identified through genome-wide association approach. However, the results have been inconclusive. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. The random-effects model was applied, addressing heterogeneity and publication bias. A total of 10 articles involving 36,221 cases and 58,108 controls were included. Overall, the summary per-allele OR of 1.19 (95 % CI 1.14-1.25, P < 10(-5)) and 1.17 (95 % CI 1.10-1.23, P < 10(-5)) was found for the rs10937405 and rs4488809 polymorphisms, respectively. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. Significant results were found in East Asians when stratified by ethnicity, whereas no significant associations were found among Caucasians. After stratifying by sample size, study design, control source and sex, significant associations were also obtained. In addition, our data indicate that these polymorphisms are involved in lung cancer susceptibility and confer its effect primarily in lung adenocarcinoma when stratified by histological subtype. Furthermore, significant associations were also detected both never-smokers and smokers for these polymorphisms. In conclusion, this meta-analysis demonstrated that rs10937405 and rs4488809 are a risk factor associated with increased non-small cell lung cancer susceptibility, particularly for East Asian populations. FAU - Jin, Yu-xing AU - Jin YX AD - Department of Thoracic Surgery, Shanghai Pulmonary Hospital Affiliated to Tongji University, No. 507 Zhengmin Rd, Shanghai, 200433, People's Republic of China. FAU - Jiang, Ge-ning AU - Jiang GN FAU - Zheng, Hui AU - Zheng H FAU - Duan, Liang AU - Duan L FAU - Ding, Jia-an AU - Ding JA LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20141025 PL - Germany TA - Mol Genet Genomics JT - Molecular genetics and genomics : MGG JID - 101093320 RN - 0 (TP63 protein, human) RN - 0 (Transcription Factors) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Case-Control Studies MH - Chromosomes, Human, Pair 3/*genetics MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Lung Neoplasms/*genetics MH - Polymorphism, Single Nucleotide MH - Risk Factors MH - Transcription Factors/*genetics MH - Tumor Suppressor Proteins/*genetics EDAT- 2014/10/26 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/10/26 06:00 PHST- 2014/05/25 [received] PHST- 2014/09/30 [accepted] PHST- 2014/10/25 [aheadofprint] AID - 10.1007/s00438-014-0934-1 [doi] PST - ppublish SO - Mol Genet Genomics. 2015 Apr;290(2):573-84. doi: 10.1007/s00438-014-0934-1. Epub 2014 Oct 25. PMID- 25318863 OWN - NLM STAT- MEDLINE DA - 20141016 DCOM- 20150519 LR - 20150113 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 9 DP - 2014 TI - Association between radiation pneumonitis and tumor response in patients with NSCLC treated with chemoradiation. PG - 217 LID - 10.1186/1748-717X-9-217 [doi] AB - Dang and colleagues recently reported in the journal that tumor response to definitive chemoradiation, as assessed using the RECIST criteria, and the risk of radiation pneumonitis were positively correlated in patients with non-small cell lung cancer (NSCLC). We had previously reported similar findings in a study that used positron tomography both to measure tumor response and to assess normal tissue toxicity in patients treated with chemoradiation for NSCLC. Taken together these reports suggest that radiosensitivity of normal tissues and tumors may be strongly linked in a proportion of patients with lung cancer. FAU - MacManus, Michael P AU - MacManus MP AD - Departments of Radiation Oncology 1 and Molecular Imaging 2, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Vic 3002, Australia. michael.macmanus@petermac.org. FAU - Ball, David AU - Ball D FAU - Hicks, Rodney J AU - Hicks RJ LA - eng PT - Comment PT - Letter DEP - 20141016 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 SB - IM CON - Radiat Oncol. 2014;9:172. PMID: 25074618 MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Carcinoma, Non-Small-Cell Lung/*therapy MH - Chemoradiotherapy/*adverse effects MH - Female MH - Humans MH - Lung Neoplasms/*therapy MH - Male MH - Radiation Pneumonitis/*diagnosis/*etiology MH - Radiotherapy, Conformal/*adverse effects MH - Radiotherapy, Intensity-Modulated/*adverse effects PMC - PMC4283112 OID - NLM: PMC4283112 EDAT- 2014/10/17 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/10/17 06:00 PHST- 2014/08/22 [received] PHST- 2014/09/12 [accepted] PHST- 2014/10/16 [aheadofprint] AID - 1748-717X-9-217 [pii] AID - 10.1186/1748-717X-9-217 [doi] PST - epublish SO - Radiat Oncol. 2014 Oct 16;9:217. doi: 10.1186/1748-717X-9-217. PMID- 25311353 OWN - NLM STAT- MEDLINE DA - 20141024 DCOM- 20150511 IS - 1759-4782 (Electronic) IS - 1759-4774 (Linking) VI - 11 IP - 11 DP - 2014 Nov TI - Lung cancer: alternative rearrangements--targeting ROS1 in NSCLC. PG - 624 LID - 10.1038/nrclinonc.2014.180 [doi] FAU - Killock, David AU - Killock D LA - eng PT - Comment PT - Journal Article DEP - 20141014 PL - England TA - Nat Rev Clin Oncol JT - Nature reviews. Clinical oncology JID - 101500077 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM CON - N Engl J Med. 2014 Nov 20;371(21):1963-71. PMID: 25264305 MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Protein Kinase Inhibitors/*therapeutic use MH - Protein-Tyrosine Kinases/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Pyrazoles/*therapeutic use MH - Pyridines/*therapeutic use EDAT- 2014/10/15 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/10/15 06:00 PHST- 2014/10/14 [aheadofprint] AID - nrclinonc.2014.180 [pii] AID - 10.1038/nrclinonc.2014.180 [doi] PST - ppublish SO - Nat Rev Clin Oncol. 2014 Nov;11(11):624. doi: 10.1038/nrclinonc.2014.180. Epub 2014 Oct 14. PMID- 25307078 OWN - NLM STAT- MEDLINE DA - 20141013 DCOM- 20150521 IS - 1024-2708 (Print) IS - 1024-2708 (Linking) VI - 20 IP - 5 DP - 2014 Oct TI - Cost-effectiveness of epidermal growth factor receptor-targeting tyrosine kinase inhibitors. PG - 465 LID - 10.12809/hkmj144336 [doi] FAU - Leung, John S M AU - Leung JS AD - St Paul's Hospital, Hong Kong. LA - eng PT - Comment PT - Letter PL - China TA - Hong Kong Med J JT - Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine JID - 9512509 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM CON - Hong Kong Med J. 2014 Jun;20(3):178-86. PMID: 24281768 MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - *Mutation MH - Protein Kinase Inhibitors/*therapeutic use MH - Quinazolines/*therapeutic use MH - Receptor, Epidermal Growth Factor/*genetics EDAT- 2014/10/14 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/10/14 06:00 PST - ppublish SO - Hong Kong Med J. 2014 Oct;20(5):465. doi: 10.12809/hkmj144336. PMID- 25288497 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150427 IS - 1532-1967 (Electronic) IS - 0305-7372 (Linking) VI - 40 IP - 10 DP - 2014 Dec TI - Infectious complications in cancer patients treated with anti-EGFR monoclonal antibodies cetuximab and panitumumab: a systematic review and meta-analysis. PG - 1221-9 LID - 10.1016/j.ctrv.2014.09.002 [doi] LID - S0305-7372(14)00149-2 [pii] AB - BACKGROUND: Clinical trials have reported a substantial variation in the risk of infection related to anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab. We performed a systematic review and meta-analysis to assess the infection risk in cancer patients treated with anti-EGFR mAbs. PATIENTS AND METHODS: We searched PubMed and the ASCO online database of meeting abstracts up to January 2014 for relevant clinical trials. Eligible studies included randomized controlled trials (RCTs) of cetuximab and panitumumab that reported adequate safety data for grade 3-4 infection or febrile neutropenia (FN). The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 14,957 patients from 28 trials were included. Treatment with anti-EGFR mAbs was associated with an increased risk of high-grade infection (RR, 1.49; 95% CI, 1.33-1.66; P<0.001) and FN (RR, 1.27; 95% CI, 1.09-1.48; P=0.002). The incidence of high-grade infection and FN due to anti-EGFR mAbs was 9.3% (95% CI, 7.2-12.0%) and 5.3% (95% CI, 3.3-8.3%), respectively. A significantly increased risk of high-grade infection was observed in all subgroups analyses (type of anti-EGFR mAb, therapy of control arm and duration of treatment) except for tumor type (only colorectal cancer and non-small cell lung cancer (NSCLC) groups had the increased risk). Subgroup analyses revealed a significantly increased risk of FN in the following subgroups: cetuximab, NSCLC and treatment duration longer than the median of all trials (3.1months). CONCLUSIONS: The use of anti-EGFR mAbs is associated with a significantly higher risk of high-grade infection and febrile neutropenia. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Funakoshi, Tomohiro AU - Funakoshi T AD - UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA. Electronic address: tomohiro.funakoshi@unchealth.unc.edu. FAU - Suzuki, Maya AU - Suzuki M AD - Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. FAU - Tamura, Kazuo AU - Tamura K AD - Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University Hospital, Fukuoka, Japan. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20140919 PL - Netherlands TA - Cancer Treat Rev JT - Cancer treatment reviews JID - 7502030 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (panitumumab) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - PQX0D8J21J (cetuximab) SB - IM MH - Antibodies, Monoclonal/administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects MH - Antineoplastic Agents/*adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy MH - Colorectal Neoplasms/drug therapy MH - Febrile Neutropenia/chemically induced MH - Humans MH - Infection/*epidemiology MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors MH - Risk Factors OTO - NOTNLM OT - Anti-EGFR monoclonal antibody OT - Cetuximab OT - Febrile neutropenia OT - Infection OT - Meta-analysis OT - Panitumumab OT - Systematic review EDAT- 2014/10/08 06:00 MHDA- 2015/04/29 06:00 CRDT- 2014/10/08 06:00 PHST- 2014/06/19 [received] PHST- 2014/09/05 [revised] PHST- 2014/09/08 [accepted] PHST- 2014/09/19 [aheadofprint] AID - S0305-7372(14)00149-2 [pii] AID - 10.1016/j.ctrv.2014.09.002 [doi] PST - ppublish SO - Cancer Treat Rev. 2014 Dec;40(10):1221-9. doi: 10.1016/j.ctrv.2014.09.002. Epub 2014 Sep 19. PMID- 25252849 OWN - NLM STAT- MEDLINE DA - 20150203 DCOM- 20150511 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 36 IP - 1 DP - 2015 Jan TI - Hu-antigen receptor (HuR) and cyclooxygenase-2 (COX-2) expression in human non-small-cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival. PG - 315-27 LID - 10.1007/s13277-014-2637-y [doi] AB - Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients' outcome (p = 0.039, p = 0.017, p = 0.033, and p = 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/COX-2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was significantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported evidence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia. FAU - Giaginis, Constantinos AU - Giaginis C AD - First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str, Goudi, Athens, 11527, Greece. FAU - Alexandrou, Paraskevi AU - Alexandrou P FAU - Tsoukalas, Nikolaos AU - Tsoukalas N FAU - Sfiniadakis, Ioannis AU - Sfiniadakis I FAU - Kavantzas, Nikolaos AU - Kavantzas N FAU - Agapitos, Emmanuel AU - Agapitos E FAU - Patsouris, Efstratios AU - Patsouris E FAU - Theocharis, Stamatios AU - Theocharis S LA - eng PT - Journal Article DEP - 20140925 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (ELAVL1 protein, human) RN - 0 (Hu Paraneoplastic Encephalomyelitis Antigens) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) SB - IM MH - Adenocarcinoma/*metabolism/mortality/pathology MH - Carcinoma, Non-Small-Cell Lung/*metabolism/mortality/pathology MH - Cell Proliferation MH - Cyclooxygenase 2/genetics/*metabolism MH - Female MH - Hu Paraneoplastic Encephalomyelitis Antigens/genetics/*metabolism MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*metabolism/mortality/pathology MH - Male MH - Middle Aged MH - Proportional Hazards Models EDAT- 2014/09/26 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/09/26 06:00 PHST- 2014/07/05 [received] PHST- 2014/09/12 [accepted] PHST- 2014/09/25 [aheadofprint] AID - 10.1007/s13277-014-2637-y [doi] PST - ppublish SO - Tumour Biol. 2015 Jan;36(1):315-27. doi: 10.1007/s13277-014-2637-y. Epub 2014 Sep 25. PMID- 25245469 OWN - NLM STAT- MEDLINE DA - 20150224 DCOM- 20150427 IS - 1439-099X (Electronic) IS - 0179-7158 (Linking) VI - 191 IP - 3 DP - 2015 Mar TI - DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily: high local control in early stage (I/II) non-small-cell lung cancer. PG - 256-63 LID - 10.1007/s00066-014-0754-6 [doi] AB - BACKGROUND: While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy >/= 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). PATIENTS AND METHODS: Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70%) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. RESULTS: The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88%, while regional control was 100%. There were 10 patients (19%) who died of the tumor, and 18 patients (33%) died due to cardiovascular or pulmonary causes. A total of 11 patients (20%) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28%) are alive. Acute esophagitis 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. FAU - Zehentmayr, Franz AU - Zehentmayr F AD - Univ.-Klinik fur Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitat, Landeskrankenhaus Salzburg, Mullner Hauptstrasse 48, 5020, Salzburg, Austria, f.zehentmayr@salk.at. FAU - Wurstbauer, Karl AU - Wurstbauer K FAU - Deutschmann, Heinz AU - Deutschmann H FAU - Fussl, Christoph AU - Fussl C FAU - Kopp, Peter AU - Kopp P FAU - Dagn, Karin AU - Dagn K FAU - Fastner, Gerd AU - Fastner G FAU - Porsch, Peter AU - Porsch P FAU - Studnicka, Michael AU - Studnicka M FAU - Sedlmayer, Felix AU - Sedlmayer F LA - eng PT - Journal Article DEP - 20140923 PL - Germany TA - Strahlenther Onkol JT - Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] JID - 8603469 SB - IM MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/*pathology/*radiotherapy MH - Cohort Studies MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/mortality/pathology/*radiotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Radiation Injuries/etiology MH - *Radiotherapy Dosage MH - *Radiotherapy Planning, Computer-Assisted MH - Survival Analysis EDAT- 2014/09/24 06:00 MHDA- 2015/04/29 06:00 CRDT- 2014/09/24 06:00 PHST- 2014/04/22 [received] PHST- 2014/09/03 [accepted] PHST- 2014/09/23 [aheadofprint] AID - 10.1007/s00066-014-0754-6 [doi] PST - ppublish SO - Strahlenther Onkol. 2015 Mar;191(3):256-63. doi: 10.1007/s00066-014-0754-6. Epub 2014 Sep 23. PMID- 25236716 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150522 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 112 IP - 2 DP - 2014 Aug TI - Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small cell lung cancer: a systematic review and meta-analysis. PG - 250-5 LID - 10.1016/j.radonc.2014.08.031 [doi] LID - S0167-8140(14)00361-2 [pii] AB - PURPOSE: A population-based matched-pair comparison was performed to compare the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC). METHODS: All the eligible studies were searched by PubMed, Medline, Embase, and the Cochrane Library. The meta-analysis was performed to compare odds ratios (OR) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local control (LC), and distant control (DC). RESULTS: Six studies containing 864 matched patients were included in the meta-analysis. The surgery was associated with a better long-term OS in patients with early-stage NSCLC. The pooled OR and 95% confidence interval (CI) for 1-year, 3-year OS were 1.31 [0.90, 1.91] and 1.82 [1.38, 2.40], respectively. However, the difference in 1-year and 3-year CSS, DFS, LC and DC was not significant. CONCLUSIONS: This systematic review found a superior 3-year OS after surgery compared with SBRT, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Zhang, Binglan AU - Zhang B AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Zhu, Fuping AU - Zhu F AD - The Department of Hepatobiliary Surgery, The Ninth People's Hospital of Chongqing, People's Republic of China. FAU - Ma, Xuelei AU - Ma X AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Tian, Ye AU - Tian Y AD - The Department of Sonography, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Cao, Dan AU - Cao D AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Luo, Songe AU - Luo S AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Xuan, Yu AU - Xuan Y AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. FAU - Liu, Lei AU - Liu L AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Electronic address: liuleihx@gmail.com. FAU - Wei, Yuquan AU - Wei Y AD - Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20140915 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 SB - IM MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery MH - Disease-Free Survival MH - Humans MH - Lung Neoplasms/pathology/*surgery MH - Matched-Pair Analysis MH - Neoplasm Staging MH - Prospective Studies MH - Radiosurgery/*methods OTO - NOTNLM OT - Lung cancer OT - Meta-analysis OT - Stereotactic body radiotherapy OT - Surgery EDAT- 2014/09/23 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/09/20 06:00 PHST- 2014/07/03 [received] PHST- 2014/08/10 [revised] PHST- 2014/08/12 [accepted] PHST- 2014/09/15 [aheadofprint] AID - S0167-8140(14)00361-2 [pii] AID - 10.1016/j.radonc.2014.08.031 [doi] PST - ppublish SO - Radiother Oncol. 2014 Aug;112(2):250-5. doi: 10.1016/j.radonc.2014.08.031. Epub 2014 Sep 15. PMID- 25227571 OWN - NLM STAT- MEDLINE DA - 20140920 DCOM- 20150512 IS - 2046-4053 (Electronic) IS - 2046-4053 (Linking) VI - 3 DP - 2014 TI - Study protocol: systematic review and meta-analysis of randomized controlled trials in first-line treatment of squamous non-small cell lung cancer. PG - 102 LID - 10.1186/2046-4053-3-102 [doi] AB - BACKGROUND: There is a high unmet need for effective treatments for patients with squamous non-small cell lung cancer (NSCLC). Eli Lilly and Company is conducting a phase III, randomized, multicenter, open-label study of gemcitabine plus cisplatin plus necitumumab (GC + N) versus gemcitabine plus cisplatin (GC) for the first-line treatment of patients with stage IV squamous NSCLC. Given GC is not the only treatment commonly used for the treatment of squamous NSCLC, this study was designed to compare the survival, toxicity, and quality of life outcomes of current treatment strategies for squamous NSCLC in the first-line setting. METHODS/DESIGN: A systematic review and meta-analysis (including indirect comparisons) of treatments used in squamous NSCLC will be conducted to assess the clinical efficacy (overall and progression-free survival), health-related quality of life (HRQoL), and safety (grade 3-4 toxicity) of GC + N compared to other treatments used in squamous NSCLC. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines will be followed for all aspects of this study. A systematic literature review will be conducted to identify randomized controlled trials evaluating chemotherapy treatment in first-line NSCLC. Eligible articles will be restricted to randomized controlled trials (RCTs) among chemotherapy-naive advanced NSCLC cancer patients that report outcome data (survival, toxicity, or quality of life) for patients with squamous histology. Following data extraction and validation, data consistency and study heterogeneity will be assessed. A network meta-analysis will be conducted based on the available hazard ratios for overall and progression-free survival, odds ratios for published toxicity data, and mean difference of HRQoL scales. Sensitivity analyses will be conducted. DISCUSSION: This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014008968. FAU - DeLozier, Amy M AU - DeLozier AM FAU - Brown, Jacqueline AU - Brown J FAU - Natanegara, Fanni AU - Natanegara F FAU - Zhao, Luping AU - Zhao L FAU - Cui, Zhanglin Lin AU - Cui ZL FAU - Able, Stephen L AU - Able SL FAU - Bowman, Lee AU - Bowman L FAU - Treat, Joseph AU - Treat J FAU - Hess, Lisa M AU - Hess LM AD - Eli Lilly and Company, Indianapolis, IN, USA. hess_lisa_m@lilly.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140916 PL - England TA - Syst Rev JT - Systematic reviews JID - 101580575 RN - 0 (Antibodies, Monoclonal) RN - 0 (IMC-11F8 monoclonal antibody) RN - 0W860991D6 (Deoxycytidine) RN - B76N6SBZ8R (gemcitabine) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antibodies, Monoclonal/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Carcinoma, Squamous Cell/*drug therapy MH - Cisplatin/administration & dosage MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Disease-Free Survival MH - Humans MH - Lung Neoplasms/*drug therapy MH - Quality of Life MH - Randomized Controlled Trials as Topic MH - *Research Design MH - Survival Rate PMC - PMC4169645 OID - NLM: PMC4169645 EDAT- 2014/09/18 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/09/18 06:00 PHST- 2014/04/23 [received] PHST- 2014/09/04 [accepted] PHST- 2014/09/16 [aheadofprint] AID - 2046-4053-3-102 [pii] AID - 10.1186/2046-4053-3-102 [doi] PST - epublish SO - Syst Rev. 2014 Sep 16;3:102. doi: 10.1186/2046-4053-3-102. PMID- 25207575 OWN - NLM STAT- MEDLINE DA - 20140911 DCOM- 20150518 IS - 1526-9914 (Electronic) IS - 1526-9914 (Linking) VI - 15 IP - 5 DP - 2014 TI - A dosimetric comparison of three-dimensional conformal radiotherapy, volumetric-modulated arc therapy, and dynamic conformal arc therapy in the treatment of non-small cell lung cancer using stereotactic body radiotherapy. PG - 4898 LID - 10.1120/jacmp.v15i5.4898 [doi] AB - This study evaluates three-dimensional conformal radiotherapy (3D CRT), volumetric-modulated arc therapy (VMAT), and dynamic conformal arc therapy (DCAT) planning techniques using dosimetric indices from Radiation Therapy Oncology Group (RTOG) protocols 0236, 0813, and 0915 for the treatment of early-stage non-small cell lung cancer (NSCLC) using stereotactic body radiotherapy (SBRT). Twenty-five clinical patients, five per lung lobe, previously treated for NSCLC using 3D CRT SBRT under respective RTOG protocols were replanned with VMAT and DCAT techniques. All plans were compared using respective RTOG dosimetric indices. High- and low-dose spillage improved for VMAT and DCAT plans, though only VMAT was able to improve dose to all organs at risk (OARs). DCAT was only able to provide a minimal improvement in dose to the heart and ipsilateral brachial plexus. Mean bilateral, contralateral, and V20 (percentage of bilateral lung receiving at least 20 Gy dose) doses were reduced with VMAT in comparison with respective 3D CRT clinical plans. Though some of the DCAT plans had values for the above indices slightly higher than their respective 3D CRT plans, they still were able to meet the RTOG constraints. VMAT and DCAT were able to offer improved skin dose by 1.1% and 11%, respectively. Monitor units required for treatment delivery increased with VMAT by 41%, but decreased with DCAT by 26%. VMAT and DCAT provided improved dose distributions to the PTV, but only VMAT was consistently superior in sparing dose to OARs in all the five lobes. DCAT should still remain an alternative to 3D CRT in facilities that do not have VMAT or intensity-modulated radiotherapy (IMRT) capabilities. FAU - Rauschenbach, Bradley M AU - Rauschenbach BM AD - Roswell Park Cancer Institute. BMRauschenbach@roswellpark.org. FAU - Mackowiak, Luke AU - Mackowiak L FAU - Malhotra, Harish K AU - Malhotra HK LA - eng PT - Comparative Study PT - Journal Article DEP - 20140908 PL - United States TA - J Appl Clin Med Phys JT - Journal of applied clinical medical physics / American College of Medical Physics JID - 101089176 SB - IM MH - Aged MH - Carcinoma, Non-Small-Cell Lung/*surgery MH - Female MH - Humans MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Radiometry/*methods MH - Radiotherapy Dosage MH - Radiotherapy Planning, Computer-Assisted/*methods MH - Radiotherapy, Conformal/*methods MH - Reproducibility of Results MH - Retrospective Studies MH - Sensitivity and Specificity MH - Treatment Outcome EDAT- 2014/09/11 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/09/11 06:00 PHST- 2014/01/13 [received] PHST- 2014/06/10 [accepted] PHST- 2014/06/16 [revised] PST - epublish SO - J Appl Clin Med Phys. 2014 Sep 8;15(5):4898. doi: 10.1120/jacmp.v15i5.4898. PMID- 25203402 OWN - NLM STAT- MEDLINE DA - 20140910 DCOM- 20150518 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 9 DP - 2014 TI - Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients. PG - e106668 LID - 10.1371/journal.pone.0106668 [doi] AB - BACKGROUND: The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. RESULTS: The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. CONCLUSIONS: The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy. FAU - Zhu, Jian-fei AU - Zhu JF AD - Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China; Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China. FAU - Feng, Xing-yu AU - Feng XY AD - Department of Gastro-pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Zhang, Xue-wen AU - Zhang XW AD - Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Wen, Ying-sheng AU - Wen YS AD - Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Lin, Peng AU - Lin P AD - Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Rong, Tie-hua AU - Rong TH AD - Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Cai, Ling AU - Cai L AD - Department of Radiation-Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Zhang, Lan-jun AU - Zhang LJ AD - Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140909 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Aged MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*pathology/*surgery MH - Chemotherapy, Adjuvant MH - China MH - Female MH - Humans MH - Lung Neoplasms/drug therapy/*pathology/*surgery MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Postoperative Period MH - Recurrence MH - Retrospective Studies MH - Risk MH - Survival Analysis MH - Time Factors PMC - PMC4159289 OID - NLM: PMC4159289 EDAT- 2014/09/10 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/09/10 06:00 PHST- 2014 [ecollection] PHST- 2014/03/30 [received] PHST- 2014/08/02 [accepted] PHST- 2014/09/09 [epublish] AID - 10.1371/journal.pone.0106668 [doi] AID - PONE-D-14-11921 [pii] PST - epublish SO - PLoS One. 2014 Sep 9;9(9):e106668. doi: 10.1371/journal.pone.0106668. eCollection 2014. PMID- 25194104 OWN - NLM STAT- MEDLINE DA - 20140907 DCOM- 20150519 IS - 1879-8500 (Print) VI - 4 IP - 5 DP - 2014 Sep-Oct TI - Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy. PG - 342-8 LID - 10.1016/j.prro.2013.12.002 [doi] LID - S1879-8500(13)00404-9 [pii] AB - PURPOSE: Chemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location. METHODS AND MATERIALS: Patients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk. RESULTS: One hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence. CONCLUSIONS: Elective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease. CI - Copyright (c) 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. FAU - Garg, Shalini AU - Garg S AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IIllinois. Electronic address: shalini_garg@rush.edu. FAU - Gielda, Benjamin T AU - Gielda BT AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IIllinois. FAU - Kiel, Krystyna AU - Kiel K AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IIllinois. FAU - Turian, Julius V AU - Turian JV AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IIllinois. FAU - Fidler, Mary Jo AU - Fidler MJ AD - Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois. FAU - Batus, Marta AU - Batus M AD - Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois. FAU - Bonomi, Philip AU - Bonomi P AD - Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois. FAU - Sher, David J AU - Sher DJ AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IIllinois. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140116 PL - United States TA - Pract Radiat Oncol JT - Practical radiation oncology JID - 101558279 SB - IM MH - Adenocarcinoma/complications/mortality/pathology/therapy MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Large Cell/complications/mortality/pathology/therapy MH - Carcinoma, Non-Small-Cell Lung/*complications/mortality/pathology/therapy MH - Carcinoma, Squamous Cell/complications/mortality/pathology/therapy MH - Chemoradiotherapy/*mortality MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*complications/mortality/pathology/therapy MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*complications/mortality/pathology/therapy MH - Neoplasm Staging MH - Prognosis MH - Radiotherapy Dosage MH - Radiotherapy Planning, Computer-Assisted MH - *Radiotherapy, Conformal MH - Retrospective Studies MH - Survival Rate MH - Tomography, X-Ray Computed EDAT- 2014/09/07 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/09/07 06:00 PHST- 2013/08/29 [received] PHST- 2013/12/04 [revised] PHST- 2013/12/04 [accepted] PHST- 2014/01/16 [aheadofprint] AID - S1879-8500(13)00404-9 [pii] AID - 10.1016/j.prro.2013.12.002 [doi] PST - ppublish SO - Pract Radiat Oncol. 2014 Sep-Oct;4(5):342-8. doi: 10.1016/j.prro.2013.12.002. Epub 2014 Jan 16. PMID- 25180631 OWN - NLM STAT- MEDLINE DA - 20140903 DCOM- 20150501 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 37 IP - 2 DP - 2014 Apr TI - ACR appropriateness Criteria(R) early-stage non-small-cell lung cancer. PG - 201-7 LID - 10.1097/COC.0000000000000013 [doi] AB - Early-stage non-small-cell lung cancer (NSCLC) is diagnosed in about 15% to 20% of lung cancer patients at presentation. In order to provide clinicians with guidance in decision making for early-stage NSCLC patients, the American College of Radiology Appropriateness Criteria Lung Cancer Panel was recently charged with a review of the current published literature to generate up-to-date management recommendations for this clinical scenario. For patients with localized, mediastinal lymph node-negative NSCLC, optimal management should be determined by an expert multidisciplinary team. For medically operable patients, surgical resection is the standard of care, with generally no role for adjuvant therapies thereafter. For patients with medical comorbidities making them at high risk for surgery, there is emerging evidence demonstrating the availability of low toxicity curative therapies, such as stereotactic body radiotherapy, for their care. As a general statement, the American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. FAU - Videtic, Gregory M M AU - Videtic GM AD - *Cleveland Clinic Foundation, Cleveland, OH daggerMD Anderson Cancer Center, Houston, TX double daggerHenry Ford Health System, Detroit, MI section signDepartment of Surgery, Columbia University parallelSociety of Thoracic Surgeons, New York, NY paragraph sign21st Century Oncology/Michigan Healthcare Professionals, Farmington Hills, MI #University of Michigan and Ann Arbor Veteran Affairs Medical Center, Ann Arbor, MI **Department of Radiation Oncology, University of Miami, Miami, FL daggerdaggerStanford University and Stanford Cancer Institute, Stanford, CA double daggerdouble daggerUniversity of North Carolina Health Care System section sign section signAmerican Society of Clinical Oncology, Chapel Hill, NC parallel parallelMassachusetts General Hospital, Boston, MA paragraph sign paragraph signMount Sinai School of Medicine, New York, NY. FAU - Chang, Joe Yujiao AU - Chang JY FAU - Chetty, Indrin J AU - Chetty IJ FAU - Ginsburg, Mark E AU - Ginsburg ME FAU - Kestin, Larry L AU - Kestin LL FAU - Kong, Feng-Ming Spring AU - Kong FM FAU - Lally, Brian E AU - Lally BE FAU - Loo, Billy W Jr AU - Loo BW Jr FAU - Movsas, Benjamin AU - Movsas B FAU - Stinchcombe, Thomas E AU - Stinchcombe TE FAU - Willers, Henning AU - Willers H FAU - Rosenzweig, Kenneth E AU - Rosenzweig KE CN - Expert Panel on Radiation OncologyLung LA - eng PT - Guideline PT - Journal Article PT - Review PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 SB - IM MH - Carcinoma, Non-Small-Cell Lung/*pathology/surgery/*therapy MH - Catheter Ablation/methods MH - Chemotherapy, Adjuvant MH - Comorbidity MH - Humans MH - Lung Neoplasms/*pathology/surgery/*therapy MH - Radiosurgery MH - Radiotherapy, Adjuvant EDAT- 2014/09/03 06:00 MHDA- 2015/05/02 06:00 CRDT- 2014/09/03 06:00 AID - 10.1097/COC.0000000000000013 [doi] AID - 00000421-201404000-00019 [pii] PST - ppublish SO - Am J Clin Oncol. 2014 Apr;37(2):201-7. doi: 10.1097/COC.0000000000000013. PMID- 25176972 OWN - NLM STAT- MEDLINE DA - 20140901 DCOM- 20150518 IS - 1600-0617 (Electronic) IS - 0905-9180 (Linking) VI - 23 IP - 133 DP - 2014 Sep TI - Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas. PG - 356-66 LID - 10.1183/09059180.00004614 [doi] AB - The discovery of epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) has allowed the identification of a subset of patients whose tumours are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Despite the efficacy and superiority of EGFR TKIs over chemotherapy as first-line therapy, all patients will ultimately develop progressive disease, with a median of 9-13 months progression-free survival. A better understanding of the molecular mechanisms underlying resistance to EGFR TKIs can help design new drugs and therapeutic strategies to overcome resistance. This has been illustrated by the new generation TKIs that are effective on the T790M mutation, which is the most frequent mechanism of acquired resistance to EGFR TKIs. In this article, we will address the main molecular mechanisms of primary and acquired resistance to EGFR TKIs in EGFR-mutant NSCLC. CI - (c)ERS 2014. FAU - Cortot, Alexis B AU - Cortot AB AD - Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Universite Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universites Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA. Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Universite Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universites Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA. alexis.cortot@chru-lille.fr. FAU - Janne, Pasi A AU - Janne PA AD - Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Universite Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universites Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA. LA - eng PT - Journal Article PT - Review PL - England TA - Eur Respir Rev JT - European respiratory review : an official journal of the European Respiratory Society JID - 9111391 RN - EC 2.7.- (Phosphotransferases) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics MH - Drug Resistance, Neoplasm MH - ErbB Receptors/*antagonists & inhibitors MH - Humans MH - Lung Neoplasms/*drug therapy/genetics MH - Mutation MH - Phenotype MH - Phosphotransferases/antagonists & inhibitors MH - Receptor, Epidermal Growth Factor/*genetics MH - Smoking EDAT- 2014/09/02 06:00 MHDA- 2015/05/20 06:00 CRDT- 2014/09/02 06:00 AID - 23/133/356 [pii] AID - 10.1183/09059180.00004614 [doi] PST - ppublish SO - Eur Respir Rev. 2014 Sep;23(133):356-66. doi: 10.1183/09059180.00004614. PMID- 25174943 OWN - NLM STAT- MEDLINE DA - 20140920 DCOM- 20150511 LR - 20141215 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 9 DP - 2014 TI - Concurrent gemcitabine and 3D radiotherapy in patients with stage III unresectable non-small cell lung cancer. PG - 190 LID - 10.1186/1748-717X-9-190 [doi] AB - BACKGROUND: Stage III unresectable non-small cell lung cancer (NSCLC) is preferably treated with concurrent schedules of chemoradiotherapy, but none is clearly superior Gemcitabine is a radiosensitizing cytotoxic drug that has been studied in phase 1 and 2 studies in this setting. The aim of this study was to describe outcome and toxicity of low-dose weekly gemcitabine combined with concurrent 3-dimensional conformal radiotherapy (3D-CRT). PATIENTS & METHODS: Treatment consisted of two cycles of a cisplatin and gemcitabine followed by weekly gemcitabine 300 mg/m2 during 5 weeks of 3D-CRT, 60 Gy in 5 weeks (hypofractionated-accelerated). Overall survival (OS), progression-free survival (PFS), and treatment related toxicity according to Common Toxicity Criteria of Adverse Events (CTCAE) version 3.0 were assessed. RESULTS: Between February 2002 and August 2008, 318 patients were treated. Median age was 64 years (range 36-86); 72% were male, WHO PS 0/1/2 was 44/53/3%. Median PFS was 15.5 months (95% confidence interval [CI], 12.9-18.1) and median OS was 24.6 months (95% CI., 21.0-28.1). Main toxicity (CTCAE grade >/=3) was dysphagia (12.6%), esophagitis (9.6%), followed by radiation pneumonitis (3.0%). There were five treatment related deaths (1.6%), two due to esophagitis and three due to radiation pneumonitis. CONCLUSION: Concurrent low-dose gemcitabine and 3D-CRT provides a comparable survival and toxicity profile to other available treatment schemes for unresectable stage III. FAU - Kerner, Gerald S M A AU - Kerner GS AD - University of Groningen and Department of Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, P,O, Box 30,001, Groningen 9700 RB, The Netherlands. g.s.m.a.kerner@umcg.nl. FAU - van Dullemen, Leon F A AU - van Dullemen LF FAU - Wiegman, Erwin M AU - Wiegman EM FAU - Widder, Joachim AU - Widder J FAU - Blokzijl, Edwin AU - Blokzijl E FAU - Driever, Ellen M AU - Driever EM FAU - van Putten, John W G AU - van Putten JW FAU - Liesker, Jeroen J W AU - Liesker JJ FAU - Renkema, Tineke E J AU - Renkema TE FAU - Pieterman, Remge M AU - Pieterman RM FAU - Mertens, Marc J F AU - Mertens MJ FAU - Hiltermann, Thijo J N AU - Hiltermann TJ FAU - Groen, Harry J M AU - Groen HJ LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140829 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 RN - 0 (Radiation-Sensitizing Agents) RN - 0W860991D6 (Deoxycytidine) RN - 5V9KLZ54CY (Vinblastine) RN - B76N6SBZ8R (gemcitabine) RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/mortality/*therapy MH - Chemoradiotherapy MH - Cisplatin/administration & dosage MH - Deoxycytidine/administration & dosage/*analogs & derivatives MH - Disease-Free Survival MH - Female MH - Humans MH - Induction Chemotherapy MH - Kaplan-Meier Estimate MH - Lung Neoplasms/mortality/*therapy MH - Male MH - Middle Aged MH - Radiation-Sensitizing Agents/*administration & dosage MH - *Radiotherapy, Conformal MH - Treatment Outcome MH - Vinblastine/administration & dosage PMC - PMC4262382 OID - NLM: PMC4262382 EDAT- 2014/09/02 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/09/02 06:00 PHST- 2014/03/22 [received] PHST- 2014/08/16 [accepted] PHST- 2014/08/29 [aheadofprint] AID - 1748-717X-9-190 [pii] AID - 10.1186/1748-717X-9-190 [doi] PST - epublish SO - Radiat Oncol. 2014 Aug 29;9:190. doi: 10.1186/1748-717X-9-190. PMID- 25157771 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - Less toxic chemotherapy improves uptake of all lines of chemotherapy in advanced non-small-cell lung cancer: a 10-year retrospective population-based review. PG - 1180-6 LID - 10.1097/JTO.0000000000000225 [doi] AB - BACKGROUND: Over the past decade, well tolerated second-line therapies for advanced non-small-cell lung cancer have been approved including erlotinib and pemetrexed in addition to docetaxel. We hypothesize that the introduction of less toxic chemotherapy has increased treatment of advanced non-small-cell lung cancer resulting in improved survival. METHODS: The BC Cancer Agency provides cancer care to 4.5 million. A retrospective review was conducted of all referred Stage IIIB/IV patients in four 1-year time cohorts; C1 baseline (1998) and 6 months after the provincial approval of C2 docetaxel (2001), C3 erlotinib (2006), and C4 pemetrexed (2007). RESULTS: Two-thousand six-hundred and twenty-three patients were referred and 720 had systemic therapy. Characteristics: M/F 55%/45%, median age 67 (33-101), ECOG PS <=1/>=2/unknown 33%/56%/11%, squam/nonsquam/NOS 18%/41%/41%. More patients received first-line chemotherapy over time; 16%, 23%, 34%, and 33% C1-C4 respectively. In C1-C4 uptake of second line (21%, 27%, 37% and 55%) increased. Second-line docetaxel was frequently used in C2 (51%) but usage decreased in C4 to 7% versus erlotinib 50% and pemetrexed 26%. The median overall survival in the best supportive care group remained stable over time; however, increased use of systemic therapy was associated with improved survival C1 9.4 m versus C4 11.8 m (p = 0.023). CONCLUSIONS: This population-based data set represents the trend of treatments over time at community and tertiary care cancer treatment sites. Over a 10-year period an increased proportion of patients were treated with first-line chemotherapy and an even greater number with second-/third-line treatment with an associated improvement in overall survival. FAU - Ho, Cheryl AU - Ho C AD - *Medical Oncology, BC Cancer Agency, Vancouver, BC; and daggerDepartment of Statistics, University of British Columbia, Vancouver, BC. FAU - Ramsden, Katherine AU - Ramsden K FAU - Zhai, Yongliang AU - Zhai Y FAU - Murray, Nevin AU - Murray N FAU - Sun, Sophie AU - Sun S FAU - Melosky, Barbara AU - Melosky B FAU - Laskin, Janessa AU - Laskin J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Glutamates) RN - 0 (Platinum Compounds) RN - 0 (Quinazolines) RN - 0 (Taxoids) RN - 04Q9AIZ7NO (pemetrexed) RN - 0W860991D6 (Deoxycytidine) RN - 15H5577CQD (docetaxel) RN - 5V9KLZ54CY (Vinblastine) RN - 5Z93L87A1R (Guanine) RN - B76N6SBZ8R (gemcitabine) RN - J4T82NDH7E (erlotinib) RN - Q6C979R91Y (vinorelbine) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Asian Continental Ancestry Group/statistics & numerical data MH - British Columbia MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/ethnology/pathology MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Drug Therapy/trends MH - Female MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Humans MH - Lung Neoplasms/*drug therapy/ethnology/pathology MH - Male MH - Middle Aged MH - Platinum Compounds/administration & dosage MH - Quinazolines/administration & dosage MH - Retrospective Studies MH - Sex Factors MH - Survival Rate/trends MH - Taxoids/administration & dosage MH - Vinblastine/administration & dosage/analogs & derivatives EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 AID - 10.1097/JTO.0000000000000225 [doi] AID - 01243894-201408000-00016 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1180-6. doi: 10.1097/JTO.0000000000000225. PMID- 25157768 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - Motesanib plus carboplatin/paclitaxel in patients with advanced squamous non-small-cell lung cancer: results from the randomized controlled MONET1 study. PG - 1154-61 LID - 10.1097/JTO.0000000000000227 [doi] AB - INTRODUCTION: The phase 3 MONET1 study evaluated motesanib (a small-molecule inhibitor of vascular endothelial growth factor receptors) plus carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC). Treatment and enrollment of patients with squamous histology were permanently discontinued following higher early mortality and gross hemoptysis in those with squamous NSCLC who received motesanib. Enrollment of patients with nonsquamous histology was temporarily halted, but resumed following a protocol amendment (Scagliotti et al. J Clin Oncol. 2012;30:2829-2836). Herein, we report data from the squamous cohort. METHODS: Patients with stage IIIB/IV or recurrent squamous NSCLC (without prior systemic therapy for advanced disease) received up to six 3-week cycles of chemotherapy (carboplatin, area under the curve 6 mg/mL*min/paclitaxel, 200 mg/m) and were randomized 1:1 to receive motesanib 125 mg (Arm A) or placebo (Arm B) once daily. The primary end point was overall survival. RESULTS: Three-hundred and sixty patients with squamous NSCLC were randomized (Arm A, n = 182; Arm B, n = 178) between July 2007 and November 2008. Twenty-three patients (13%) in Arm A and 10 (6%) in Arm B had fatal adverse events within the first 60 days of treatment. Among these, six patients in Arm A, but none in Arm B, had fatal bleeding events. At final analysis, serious adverse events had occurred in 47% of patients in Arm A and 29% of patients in Arm B. Median overall survival was similar in Arms A and B (11.1 versus 10.7 months). CONCLUSIONS: Motesanib plus carboplatin/paclitaxel had unacceptable toxicity compared with carboplatin/paclitaxel alone in patients with advanced squamous NSCLC. FAU - Novello, Silvia AU - Novello S AD - *Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy; daggerThoracic Surgery Department, Zaporizhzhya State Medical University, Zaporizhzhya, Ukraine; double daggerSumy Regional Oncology Centre, Sumy State University, Sumy, Ukraine; section signCentrul de Oncologie Medicala, Iasi, Romania; ||Central Hospital Bad Berka, Bad Berka, Germany; paragraph signDepartment of Medical Oncology, The Christie National Health Services Foundation Trust, Manchester, United Kingdom; #Department of Biostatistics & Epidemiology, Amgen Inc., South San Francisco; **Department of Oncology, Amgen Inc., Thousand Oaks, CA; and daggerdaggerSarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN. FAU - Scagliotti, Giorgio V AU - Scagliotti GV FAU - Sydorenko, Oleksandr AU - Sydorenko O FAU - Vynnychenko, Ihor AU - Vynnychenko I FAU - Volovat, Constantin AU - Volovat C FAU - Schneider, Claus-Peter AU - Schneider CP FAU - Blackhall, Fiona AU - Blackhall F FAU - McCoy, Sheryl AU - McCoy S FAU - Hei, Yong-Jiang AU - Hei YJ FAU - Spigel, David R AU - Spigel DR LA - eng SI - ClinicalTrials.gov/NCT00460317 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Indoles) RN - 25X51I8RD4 (Niacinamide) RN - 33069-62-4 (Paclitaxel) RN - BG3F62OND5 (Carboplatin) RN - F60NE4XB53 (imetelstat) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - Carcinoma, Squamous Cell/*drug therapy/pathology MH - Disease-Free Survival MH - Double-Blind Method MH - Early Termination of Clinical Trials MH - Female MH - Hemoptysis/*chemically induced MH - Humans MH - Indoles/administration & dosage/adverse effects MH - Lung Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Niacinamide/administration & dosage/adverse effects/analogs & derivatives MH - Paclitaxel/administration & dosage MH - Survival Rate EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 AID - 10.1097/JTO.0000000000000227 [doi] AID - 01243894-201408000-00013 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1154-61. doi: 10.1097/JTO.0000000000000227. PMID- 25157767 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 LR - 20150425 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - NCCTG N0821 (Alliance): a phase II first-line study of pemetrexed, carboplatin, and bevacizumab in elderly patients with advanced nonsquamous non-small-cell lung cancer with good performance status. PG - 1146-53 LID - 10.1097/JTO.0000000000000217 [doi] AB - BACKGROUND: We hypothesized that the combination of bevacizumab, carboplatin, and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous non-small-cell lung cancer. METHODS: Treatment-naive, stage IIIB/IV nonsquamous non-small-cell lung cancer patients more than 70 years old with good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were eligible. Carboplatin area under the curve 6, pemetrexed 500 mg/m, and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to six cycles) followed by maintenance pemetrexed and bevacizumab. The primary end point of 6-month progression-free survival rate of at least 70% was assessed using a one-stage binomial design. Quality of life (QOL) questionnaires were administered. Polymorphisms in genes encoding relevant proteins (drug targets, transport, and metabolism proteins) were correlated with treatment outcome. RESULTS: Fifty-seven eligible patients were enrolled. Median age was 74.5 years. Median treatment cycles received was 6. The most common grade 3 or higher non-hematologic adverse events were fatigue (26%) and hypertension (11%); 16% had grade 4 neutropenia and 6.5% had grade 4 thrombocytopenia. Three patients experienced grade 3/4 hemorrhagic events (one pulmonary, two gastrointestinal). Primary end point of PFS6 was 60% (95% confidence interval [CI]: 45.9-73%). Median PFS was 7.0 months (95% CI: 5.9-10.1), median overall survival was 13.7 months (95% CI: 9.4-16.8). Polymorphic KDR and VEGFA variants correlated with survival and toxicity, respectively. There was no significant change in overall QOL scores over time. CONCLUSION: This regimen is feasible and did not decrease the QOL in this study population. However, it did not meet the primary efficacy end point. FAU - Dy, Grace K AU - Dy GK AD - *Roswell Park Cancer Institute, Buffalo, NY; daggerMayo Clinic Rochester, MN 55905; double daggerMichiana Hematology Oncology, South Bend, IN; section signIllinois CancerCare, Ottawa, IL; ||Mayo Clinic Scottsdale, AZ; paragraph signMissouri Valley Cancer Consortium, Omaha, NE; and #Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN. FAU - Molina, Julian R AU - Molina JR FAU - Qi, Yingwei AU - Qi Y FAU - Ansari, Rafat AU - Ansari R FAU - Thomas, Sachdev AU - Thomas S FAU - Ross, Helen J AU - Ross HJ FAU - Soori, Gamini AU - Soori G FAU - Anderson, Daniel AU - Anderson D FAU - Aubry, Marie Christine AU - Aubry MC FAU - Meyers, Jeffrey AU - Meyers J FAU - Adjei, Araba A AU - Adjei AA FAU - Mandrekar, Sumithra AU - Mandrekar S FAU - Adjei, Alex A AU - Adjei AA LA - eng GR - CA-25224/CA/NCI NIH HHS/United States GR - CA-35090/CA/NCI NIH HHS/United States GR - CA-35103/CA/NCI NIH HHS/United States GR - CA-35113/CA/NCI NIH HHS/United States GR - CA-35267/CA/NCI NIH HHS/United States GR - CA-35269/CA/NCI NIH HHS/United States GR - CA-35415/CA/NCI NIH HHS/United States GR - CA-37404/CA/NCI NIH HHS/United States GR - CA-63848/CA/NCI NIH HHS/United States GR - CA-63849/CA/NCI NIH HHS/United States GR - U10 CA025224/CA/NCI NIH HHS/United States GR - U10 CA180866/CA/NCI NIH HHS/United States GR - UG1 CA189823/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Glutamates) RN - 0 (Reduced Folate Carrier Protein) RN - 0 (SLC19A1 protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 04Q9AIZ7NO (pemetrexed) RN - 2S9ZZM9Q9V (bevacizumab) RN - 5Z93L87A1R (Guanine) RN - BG3F62OND5 (Carboplatin) RN - EC 2.1.1.45 (Thymidylate Synthase) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/pathology MH - Disease-Free Survival MH - Fatigue/chemically induced MH - Female MH - Genotype MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Hemorrhage/chemically induced MH - Humans MH - Hypertension/chemically induced MH - Lung Neoplasms/*drug therapy/*genetics/pathology MH - Male MH - Neutropenia/chemically induced MH - Patient Acuity MH - Polymorphism, Single Nucleotide MH - Quality of Life MH - Reduced Folate Carrier Protein/genetics MH - Survival Rate MH - Thrombocytopenia/chemically induced MH - Thymidylate Synthase/genetics MH - Vascular Endothelial Growth Factor A/genetics MH - Vascular Endothelial Growth Factor Receptor-2/genetics PMC - PMC4145612 MID - NIHMS586371 OID - NLM: NIHMS586371 [Available on 08/01/15] OID - NLM: PMC4145612 [Available on 08/01/15] EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 PMCR- 2015/08/01 00:00 AID - 10.1097/JTO.0000000000000217 [doi] AID - 01243894-201408000-00012 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1146-53. doi: 10.1097/JTO.0000000000000217. PMID- 25157765 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - Comparison of the yield of different diagnostic procedures for cellular differentiation and genetic profiling of non-small-cell lung cancer. PG - 1120-5 LID - 10.1097/JTO.0000000000000230 [doi] AB - INTRODUCTION: As treatments for non-small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation. METHODS: We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples. RESULTS: We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients. CONCLUSION: Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC. FAU - Albanna, Amr S AU - Albanna AS AD - *Department of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; daggerDivision of Pulmonary Diseases, Department of Internal Medicine; double daggerDepartment of Oncology; and section signDepartment of Pathology, Jewish General Hospital, McGill University, Montreal, Canada. FAU - Kasymjanova, Goulnar AU - Kasymjanova G FAU - Robitaille, Chantal AU - Robitaille C FAU - Cohen, Victor AU - Cohen V FAU - Brandao, Guilherme AU - Brandao G FAU - Pepe, Carmela AU - Pepe C FAU - Small, David AU - Small D FAU - Agulnik, Jason AU - Agulnik J LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Aged MH - Aged, 80 and over MH - Biopsy, Needle/methods MH - Bronchoalveolar Lavage Fluid/cytology MH - Carcinoma, Non-Small-Cell Lung/*genetics/*pathology/surgery MH - Cell Differentiation MH - Female MH - Gene Expression Profiling MH - Humans MH - Image-Guided Biopsy MH - Lung/*pathology MH - Lung Neoplasms/*genetics/*pathology/surgery MH - Male MH - Middle Aged MH - Mutation MH - Pleural Effusion/pathology MH - Receptor, Epidermal Growth Factor/*genetics EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 AID - 10.1097/JTO.0000000000000230 [doi] AID - 01243894-201408000-00009 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1120-5. doi: 10.1097/JTO.0000000000000230. PMID- 25157764 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - Circulating tumor microemboli diagnostics for patients with non-small-cell lung cancer. PG - 1111-9 LID - 10.1097/JTO.0000000000000235 [doi] AB - INTRODUCTION: Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation. METHODS: First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group. RESULTS: We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002). CONCLUSION: CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform. FAU - Carlsson, Anders AU - Carlsson A AD - *The Scripps Research Institute, Department of Cell Biology, La Jolla, CA; daggerDepartment of Medicine, Stanford University School of Medicine Stanford, CA; double daggerCentre Hospitalier de l'Universite de Sherbrooke, Department of Nuclear Medicine and Radiobiology, Sherbrooke, Quebec; section signThe California Pacific Medical Center Research Institute, San Francisco, CA; ||The VA Palo Alto Health Care System, Section of Nuclear Medicine, Palo Alto, CA; paragraph signDepartment of Radiology, Stanford University School of Medicine, Stanford, CA; #The VA Palo Alto Health Care System Section of Pulmonary & Critical Care, Palo Alto, CA; **Department of Radiation Oncology; daggerdaggerDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA; double daggerdouble daggerThe VA Palo Alto Health Care System Section of Cardiothoracic Surgery, Palo Alto, CA; section sign section signScripps Clinic, Department of Pathology, La Jolla, CA; || ||Nuclear Medicine Division, University of San Diego Medical Center, San Diego, CA; paragraph sign paragraph signThe Moores Cancer Center, University of San Diego Medical Center, La Jolla, CA; ##The Billings Clinic, Department of Hematology/Oncology, Billings, MT; ***Departments of Bioengineering and daggerdaggerdaggerMaterials Science and Engineering, Stanford University School of Medicine, Stanford, CA. FAU - Nair, Viswam S AU - Nair VS FAU - Luttgen, Madelyn S AU - Luttgen MS FAU - Keu, Khun Visith AU - Keu KV FAU - Horng, George AU - Horng G FAU - Vasanawala, Minal AU - Vasanawala M FAU - Kolatkar, Anand AU - Kolatkar A FAU - Jamali, Mehran AU - Jamali M FAU - Iagaru, Andrei H AU - Iagaru AH FAU - Kuschner, Ware AU - Kuschner W FAU - Loo, Billy W Jr AU - Loo BW Jr FAU - Shrager, Joseph B AU - Shrager JB FAU - Bethel, Kelly AU - Bethel K FAU - Hoh, Carl K AU - Hoh CK FAU - Bazhenova, Lyudmila AU - Bazhenova L FAU - Nieva, Jorge AU - Nieva J FAU - Kuhn, Peter AU - Kuhn P FAU - Gambhir, Sanjiv S AU - Gambhir SS LA - eng GR - P50 CA114747/CA/NCI NIH HHS/United States GR - P50CA114747/CA/NCI NIH HHS/United States GR - R33 CA173373/CA/NCI NIH HHS/United States GR - U54 CA119367/CA/NCI NIH HHS/United States GR - U54 CA119367/CA/NCI NIH HHS/United States GR - U54 CA143906/CA/NCI NIH HHS/United States GR - U54 CA151459/CA/NCI NIH HHS/United States GR - U54 CA151459/CA/NCI NIH HHS/United States GR - U54CA143906/CA/NCI NIH HHS/United States GR - UL1 RR025744/RR/NCRR NIH HHS/United States GR - UL1 RR025744/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Indoles) RN - 0 (Radiopharmaceuticals) RN - 0 (Tumor Markers, Biological) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - 47165-04-8 (DAPI) RN - 68238-35-7 (Keratins) RN - EC 3.1.3.48 (Antigens, CD45) RN - EC 3.1.3.48 (PTPRC protein, human) SB - IM MH - Aged MH - Aged, 80 and over MH - Antigens, CD45/analysis MH - Area Under Curve MH - Carcinoma, Non-Small-Cell Lung/*diagnosis MH - Embolism/*pathology MH - Female MH - Fluorodeoxyglucose F18/diagnostic use MH - Humans MH - Indoles/analysis MH - Keratins/analysis MH - Lung Neoplasms/*diagnosis MH - Male MH - Middle Aged MH - Multimodal Imaging MH - Neoplasm Staging MH - Neoplastic Cells, Circulating/chemistry/*pathology MH - Positron-Emission Tomography MH - Prospective Studies MH - Radiopharmaceuticals/diagnostic use MH - Risk Assessment MH - Tomography, X-Ray Computed MH - Tumor Burden MH - *Tumor Markers, Biological PMC - PMC4145608 MID - NIHMS590665 OID - NLM: NIHMS590665 [Available on 08/01/15] OID - NLM: PMC4145608 [Available on 08/01/15] EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 PMCR- 2015/08/01 00:00 AID - 10.1097/JTO.0000000000000235 [doi] AID - 01243894-201408000-00008 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1111-9. doi: 10.1097/JTO.0000000000000235. PMID- 25157761 OWN - NLM STAT- MEDLINE DA - 20140827 DCOM- 20150514 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 8 DP - 2014 Aug TI - Non-small-cell lung cancer after breast cancer: a population-based study of clinicopathologic characteristics and survival outcomes in 3529 women. PG - 1081-90 LID - 10.1097/JTO.0000000000000213 [doi] AB - INTRODUCTION: Annually, 1.4 million women worldwide are diagnosed with breast cancer (BC) and are at risk for another common malignancy: non-small-cell lung cancer (NSCLC). No large population-based study has examined subsequent survival. METHODS: Women with histologically confirmed NSCLC after BC (BC-NSCLC, n = 3529) were identified in SEER-18 registries (1988-2009). Clinicopathologic characteristics and survival outcomes were compared among women with first primary NSCLC (NSCLC-1, n = 151,628). Cox regression analyses were adjusted for patient, BC, and NSCLC factors. RESULTS: BC-NSCLC was diagnosed at earlier stages (34% localized, 30% regional, 36% distant) than NSCLC-1 (22%, 28%, and 50%, respectively; p < 0.0001). For localized and regional BC-NSCLC, surgical resection rates were higher than NSCLC-1 (72% versus 69% [p < 0.01] and 56% versus 46% [p < 0.0001]), respectively). Radiotherapy was given less often for BC-NSCLC than NSCLC-1 (localized: 15% versus 18%, p < 0.004; regional: 38% versus 49%, p < 0.0001). Median overall survival (OS) after localized, regional, and distant BC-NSCLC was 5.1 years, 1.9 years, and 5.8 months, respectively. For NSCLC-1, median OS was 4.6 years, 1.5 years, and 4.6 months, respectively. BC history did not affect OS for localized NSCLC, and OS was modestly greater after regional (p = 0.016) and distant (p < 0.0001) BC-NSCLC compared with NSCLC-1. BC radiotherapy to the ipsilateral chest did not unfavorably influence OS. CONCLUSIONS: BC survivors are more likely to be diagnosed with earlier stage NSCLC versus first primary NSCLC patients, perhaps reflecting heightened surveillance compared with the general population. In contrast to prior studies of NSCLC in survivors of lymphopoietic malignancies, BC history does not appear to adversely affect OS after NSCLC. FAU - Milano, Michael T AU - Milano MT AD - *Department of Radiation Oncology and Rubin Center for Cancer Survivorship; and daggerDepartment of Biostatistics and Computational Biology, University of Rochester School of Medicine, Rochester, NY. FAU - Strawderman, Robert L AU - Strawderman RL FAU - Venigalla, Sriram AU - Venigalla S FAU - Ng, Kimberly AU - Ng K FAU - Travis, Lois B AU - Travis LB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Receptors, Estrogen) SB - IM MH - Aged MH - Aged, 80 and over MH - Breast Neoplasms/*mortality/pathology/therapy MH - Carcinoma, Non-Small-Cell Lung/*mortality/secondary/therapy MH - Early Detection of Cancer MH - Female MH - Humans MH - Lung Neoplasms/*mortality/*pathology/therapy MH - Middle Aged MH - Neoplasm Staging MH - Neoplasms, Second Primary/*mortality/*pathology/therapy MH - Receptors, Estrogen/analysis MH - SEER Program MH - Survival Rate EDAT- 2014/08/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/27 06:00 AID - 10.1097/JTO.0000000000000213 [doi] AID - 01243894-201408000-00005 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Aug;9(8):1081-90. doi: 10.1097/JTO.0000000000000213. PMID- 25154893 OWN - NLM STAT- MEDLINE DA - 20140902 DCOM- 20150511 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 9 DP - 2014 TI - Locoregional tumor failure after definitive radiation for patients with stage III non-small cell lung cancer. PG - 187 LID - 10.1186/1748-717X-9-187 [doi] AB - BACKGROUND: Locoregional tumor failure (LRF) after definitive chemoradiation for patients with stage III NSCLC remains unacceptably high. This analysis sought to further define where LRF occurs relative to radiation dose received and pre-treatment PET scan-defined maximum standard uptake value (SUVmax). METHODS: This was a retrospective study analyzing patients with stage III NSCLC treated with definitive radiation between 2006 and 2011. LRF was defined as failure within the ipsilateral lung, hilum or mediastinum. The CT simulation scan with the radiation dose distribution was registered to the CT or PET/CT documenting LRF. The region of LRF was contoured, and the dose to 95% of the volume (D95) of LRF was extracted. The pre-treatment SUVmax was also extracted for the anatomic region of LRF. RESULTS: Sixty-one patients were identified. Median follow-up time was 19.1 months (range 2.37-76.33). Seventy four percent of patients were treated with 3-D conformal technique (3DCRT), 15% were treated with Intensity Modulated Radiotherapy (IMRT), and 11% were treated with a combination of 3DCRT and IMRT. Median prescribed radiation dose for all patients was 66 Gy (39.6-74). Concurrent chemotherapy was delivered in 90% of patients. Twenty-two patients (36%) developed a LRF, with a total of 39 anatomic regions of LRF identified. Median time to LRF was 11.4 months (3.5-44.6). Failures were distributed as follows: 36% were in-field failures, 27% were out-of-field failures, 18% were in-field and out-of-field failures, and 18% were in-field and marginal (recurrences within the field edge) failures. There were no isolated marginal failures. Of the patients that developed a LRF, 73% developed a LRF with an in-field component. Sixty-two percent of LRFs were nodal. The median pre-treatment SUVmax for the anatomic region of LRF for patients with an in-field failure was 13. The median D95 of in-field LRF was 63 Gy. CONCLUSIONS: LRF after definitive chemoradiation are comprised primarily of in-field failures, though out-of field failures are not insignificant. Marginal failures are rare, indicating field margins are appropriate. Although radiation dose escalation to standard radiation fields has not yielded success, using PET parameters to define high-risk regions remains worthy of further investigation. FAU - Rajpara, Raj S AU - Rajpara RS FAU - Schreibmann, Eduard AU - Schreibmann E FAU - Fox, Tim AU - Fox T FAU - Stapleford, Liza J AU - Stapleford LJ FAU - Beitler, Jonathan J AU - Beitler JJ FAU - Curran, Walter J AU - Curran WJ FAU - Higgins, Kristin A AU - Higgins KA AD - Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. kristin.higgins@emory.edu. LA - eng PT - Journal Article DEP - 20140826 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 SB - IM MH - Adult MH - Aged MH - Carcinoma, Non-Small-Cell Lung/pathology/*radiotherapy MH - Chemoradiotherapy MH - Female MH - Humans MH - Lung Neoplasms/pathology/*radiotherapy MH - Male MH - Middle Aged MH - Multimodal Imaging MH - Neoplasm Recurrence, Local/*epidemiology MH - Neoplasm Staging MH - Radiotherapy Dosage MH - *Radiotherapy, Conformal MH - *Radiotherapy, Intensity-Modulated MH - Retrospective Studies MH - Treatment Outcome PMC - PMC4155086 OID - NLM: PMC4155086 EDAT- 2014/08/27 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/27 06:00 PHST- 2014/05/12 [received] PHST- 2014/08/16 [accepted] PHST- 2014/08/26 [aheadofprint] AID - 1748-717X-9-187 [pii] AID - 10.1186/1748-717X-9-187 [doi] PST - epublish SO - Radiat Oncol. 2014 Aug 26;9:187. doi: 10.1186/1748-717X-9-187. PMID- 25150635 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150522 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 112 IP - 2 DP - 2014 Aug TI - Cisplatin vs. carboplatin-based chemoradiotherapy in patients >65 years of age with stage III non-small cell lung cancer. PG - 272-8 LID - 10.1016/j.radonc.2014.07.014 [doi] LID - S0167-8140(14)00320-X [pii] AB - BACKGROUND AND PURPOSE: Combined chemoradiotherapy (CRT) is considered the standard care for unresectable stage III non-small cell lung cancer (NSCLC). There have been limited data comparing outcomes of carboplatin vs. cisplatin-based CRT, particularly in elderly. MATERIAL AND METHODS: From the Surveillance, Epidemiology and End Results-Medicare registry, we identified 1878 patients >65 years of age with unresected stage III NSCLC that received concurrent CRT between 2002 and 2009. We fitted a propensity score model predicting use of cisplatin-based therapy and compared adjusted overall and lung-cancer specific survival of carboplatin- vs. cisplatin-treated patients. Rates of severe toxicity requiring hospital admission were compared in propensity score adjusted analyses. RESULTS: Overall 1552 (83%) received carboplatin (77% in combination with paclitaxel) and 17% cisplatin (67% in combination with etoposide). Adjusted cox models showed similar overall (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.86-1.12) and lung cancer-specific (HR: 0.99; 95% CI: 0.84-1.17) survival among patients treated with carboplatin vs. cisplatin. Adjusted rates of neutropenia (odds ratio [OR]: 0.35; 95% CI: 0.21-0.61), anemia (OR: 0.67; 95% CI: 0.51-0.89), and thrombocytopenia (OR: 0.51; 95% CI: 0.31-0.85) were lower among carboplatin-treated patients; other toxicities were not different between groups. CONCLUSION: Carboplatin-based CRT is associated with similar long-term survival but lower rates of toxicity. These findings suggest carboplatin may be the most appropriate chemotherapeutic agent for elderly stage III patients. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Ezer, Nicole AU - Ezer N AD - Department of Medicine, Respiratory Division and Respiratory Epidemiology and Clinical Research Unit, McGill University, Montreal, Canada; Divisions of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, United States. Electronic address: nicole.ezer@mountsinai.org. FAU - Smith, Cardinale B AU - Smith CB AD - Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States; Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, United States. FAU - Galsky, Matthew D AU - Galsky MD AD - Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States. FAU - Mhango, Grace AU - Mhango G AD - Divisions of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, United States. FAU - Gu, Fei AU - Gu F AD - Department of Medicine, UMass Memorial Medical Center, United States. FAU - Gomez, Jorge AU - Gomez J AD - Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States. FAU - Strauss, Gary M AU - Strauss GM AD - Department of Medicine, Tufts University School of Medicine, Boston, United States; Division of Hematology-Oncology, Tufts Medical Center, Boston, United States. FAU - Wisnivesky, Juan AU - Wisnivesky J AD - Divisions of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, United States; Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140820 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 RN - 33069-62-4 (Paclitaxel) RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology/*radiotherapy MH - Chemoradiotherapy/methods MH - Cisplatin/administration & dosage MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/pathology/*radiotherapy MH - Male MH - Neoplasm Staging MH - Paclitaxel/administration & dosage MH - Proportional Hazards Models MH - Randomized Controlled Trials as Topic MH - SEER Program MH - Survival Rate MH - United States/epidemiology OTO - NOTNLM OT - Carboplatin OT - Chemoradiotherapy OT - Cisplatin OT - Elderly OT - Non small cell lung cancer EDAT- 2014/08/26 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/08/25 06:00 PHST- 2014/06/06 [received] PHST- 2014/07/23 [revised] PHST- 2014/07/26 [accepted] PHST- 2014/08/20 [aheadofprint] AID - S0167-8140(14)00320-X [pii] AID - 10.1016/j.radonc.2014.07.014 [doi] PST - ppublish SO - Radiother Oncol. 2014 Aug;112(2):272-8. doi: 10.1016/j.radonc.2014.07.014. Epub 2014 Aug 20. PMID- 25145405 OWN - NLM STAT- MEDLINE DA - 20140822 DCOM- 20150512 IS - 0386-300X (Print) IS - 0386-300X (Linking) VI - 68 IP - 4 DP - 2014 TI - Drug resistance to EGFR tyrosine kinase inhibitors for non-small cell lung cancer. PG - 191-200 AB - Non-small cell lung cancer (NSCLC) harboring an activating mutation within the epidermal growth factor receptor (EGFR) was defined as a clinically distinct molecular group. These lesions show oncogene addiction to EGFR and dramatic responses to the EGFR tyrosine kinase inhibitors (TKIs). Several large Phase III trials have shown that EGFR-TKIs improved the progression-free survival of patients with EGFR mutant NSCLC compared to conventional chemotherapy. However, the long-term effectiveness of EGFR-TKIs is usually limited because of acquired drug resistance. To overcome this resistance to EGFR-TKIs, it will be essential to identify the specific mechanisms underlying the resistance. Many investigators have attempted to identify the mechanisms using preclinical models and drug-resistant clinical samples. As a result, several mechanisms have been showed to be responsible for the resistance, but not all of the relevant mechanisms have been uncovered. In this review, we provide an overview of mechanisms underlying drug-resistance to EGFR-TKIs, focusing on results obtained with preclinical models, and we present some possible strategies to overcome the EGFR-TKI resistance. FAU - Shien, Kazuhiko AU - Shien K AD - Departments of Clinical Genomic Medicine, and General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. FAU - Yamamoto, Hiromasa AU - Yamamoto H FAU - Soh, Junichi AU - Soh J FAU - Miyoshi, Shinichiro AU - Miyoshi S FAU - Toyooka, Shinichi AU - Toyooka S LA - eng PT - Journal Article PT - Review PL - Japan TA - Acta Med Okayama JT - Acta medica Okayama JID - 0417611 RN - 0 (Antineoplastic Agents) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Drug Resistance, Neoplasm MH - Humans MH - Receptor, Epidermal Growth Factor/*antagonists & inhibitors EDAT- 2014/08/26 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/23 06:00 PST - ppublish SO - Acta Med Okayama. 2014;68(4):191-200. PMID- 25136582 OWN - NLM STAT- MEDLINE DA - 20140819 DCOM- 20150511 LR - 20150322 IS - 2314-6141 (Electronic) VI - 2014 DP - 2014 TI - Proton-based stereotactic ablative radiotherapy in early-stage non-small-cell lung cancer. PG - 389048 LID - 10.1155/2014/389048 [doi] AB - Stereotactic ablative radiotherapy (SABR), a recent implementation in the practice of radiation oncology, has been shown to confer high rates of local control in the treatment of early stage non-small-cell lung cancer (NSCLC). This technique, which involves limited invasive procedures and reduced treatment intervals, offers definitive treatment for patients unable or unwilling to undergo an operation. The use of protons in SABR delivery confers the added physical advantage of normal tissue sparing due to the absence of collateral radiation dose delivered to regions distal to the target. This may translate into clinical benefit and a decreased risk of clinical toxicity in patients with nearby critical structures or limited pulmonary reserve. In this review, we present the rationale for proton-based SABR, principles relating to the delivery and planning of this modality, and a summary of published clinical studies. FAU - Grant, Jonathan D AU - Grant JD AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. FAU - Chang, Joe Y AU - Chang JY AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Review DEP - 20140717 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 SB - IM MH - Carcinoma, Non-Small-Cell Lung/pathology/*therapy MH - Humans MH - Lung Neoplasms/pathology/*therapy MH - Proton Therapy/*methods MH - Radiosurgery/*methods PMC - PMC4124720 OID - NLM: PMC4124720 EDAT- 2014/08/20 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/20 06:00 PHST- 2014/04/04 [received] PHST- 2014/05/30 [revised] PHST- 2014/06/21 [accepted] PHST- 2014/07/17 [epublish] AID - 10.1155/2014/389048 [doi] PST - ppublish SO - Biomed Res Int. 2014;2014:389048. doi: 10.1155/2014/389048. Epub 2014 Jul 17. PMID- 25122441 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - EGFR mutations in Asian patients with advanced lung adenocarcinoma. PG - e70-1 LID - 10.1097/JTO.0000000000000251 [doi] FAU - Liam, Chong-Kin AU - Liam CK AD - Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. FAU - Pang, Yong-Kek AU - Pang YK FAU - Poh, Mau-Ern AU - Poh ME LA - eng PT - Comment PT - Letter PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM CON - J Thorac Oncol. 2014 Feb;9(2):154-62. PMID: 24419411 MH - Adenocarcinoma/*genetics MH - Adenocarcinoma, Bronchiolo-Alveolar/*genetics MH - Asian Continental Ancestry Group/*genetics MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Female MH - Humans MH - Lung Neoplasms/*genetics MH - Male MH - Mutation/*genetics MH - Receptor, Epidermal Growth Factor/*genetics EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000251 [doi] AID - 01243894-201409000-00031 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):e70-1. doi: 10.1097/JTO.0000000000000251. PMID- 25122440 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Cisplatin or Carboplatin for advanced non-small-cell lung cancer? PG - e70 LID - 10.1097/JTO.0000000000000246 [doi] FAU - Sun, Xiaoli AU - Sun X AD - Department of Radiotherapy, The First Affiliated Hospital of Zhejiang University, Hangzhou, China Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China. FAU - Zheng, Yulong AU - Zheng Y LA - eng PT - Comment PT - Letter PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) SB - IM CON - J Thorac Oncol. 2014 May;9(5):702-9. PMID: 24662458 MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/*administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Cisplatin/*administration & dosage MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000246 [doi] AID - 01243894-201409000-00030 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):e70. doi: 10.1097/JTO.0000000000000246. PMID- 25122437 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS). PG - 1411-7 LID - 10.1097/JTO.0000000000000274 [doi] AB - INTRODUCTION: ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. METHODS: Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485-0.914; p = 0.0105). No OS benefit of B+E was observed. CONCLUSIONS: Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study. FAU - Kabbinavar, Fairooz AU - Kabbinavar F AD - *University of California Los Angeles, Los Angeles, CA; daggerKaiser Permanente Northern CA, Antioch, CA; double daggerSarah Cannon Research Institute, Nashville, TN; section signNorthwest Medical Specialties, Tacoma, WA; ||Sibley Memorial Hospital, Washington, DC; paragraph signIntegrated Community Oncology Network, Jacksonville, FL; #The Mark H. Zangmeister Center, Columbus, OH; **Florida Cancer Specialists, Bonita Springs, FL; daggerdaggerArch Medical Services Inc., The Center for Cancer Care and Research, Saint Louis, MO; double daggerdouble daggerNational Taiwan University, Taipei, Taiwan; section sign section signF. Hoffmann-La Roche Ltd., Basel, Switzerland; || ||Genentech Inc., South San Francisco, CA; paragraph sign paragraph signWeill Cornell Medical College and Thoracic Oncology Service, New York, NY; and ##Dana-Farber Cancer Institute, Boston, MA. FAU - Fehrenbacher, Louis AU - Fehrenbacher L FAU - Hainsworth, John AU - Hainsworth J FAU - Kasubhai, Saifuddin AU - Kasubhai S FAU - Kressel, Bruce AU - Kressel B FAU - Marsland, Thomas AU - Marsland T FAU - Patel, Taral AU - Patel T FAU - Rubin, Mark AU - Rubin M FAU - White, Leonard AU - White L FAU - Yang, James Chih-Hsin AU - Yang JC FAU - Klughammer, Barbara AU - Klughammer B FAU - Colburn, Dawn AU - Colburn D FAU - Miller, Vincent AU - Miller V FAU - Johnson, Bruce E AU - Johnson BE LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - 0 (Tumor Markers, Biological) RN - 0 (Vascular Endothelial Growth Factor A) RN - 2S9ZZM9Q9V (bevacizumab) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Angiogenesis Inhibitors/therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/mortality MH - Disease-Free Survival MH - Drug Therapy, Combination MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/metabolism/mortality MH - Male MH - Middle Aged MH - Protein Kinase Inhibitors/therapeutic use MH - Quinazolines/*therapeutic use MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors MH - Survival Rate/trends MH - Tumor Markers, Biological/*metabolism MH - United States/epidemiology MH - Vascular Endothelial Growth Factor A MH - Young Adult EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000274 [doi] AID - 01243894-201409000-00027 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1411-7. doi: 10.1097/JTO.0000000000000274. PMID- 25122433 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Toxicities of organs at risk in the mediastinal and hilar regions following stereotactic body radiotherapy for centrally located lung tumors. PG - 1370-6 LID - 10.1097/JTO.0000000000000260 [doi] AB - INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility. FAU - Nishimura, Shuichi AU - Nishimura S AD - *Radiation Oncology Center, Ofuna Chuo Hospital, Kanagawa, Japan; daggerDepartment of Radiology, Juntendo University School of Medicine, Tokyo, Japan; double daggerDepartment of Radiology, Tokai University School of Medicine, Kanagawa, Japan; and section signDepartment of Radiology, Keio University School of Medicine, Tokyo, Japan. FAU - Takeda, Atsuya AU - Takeda A FAU - Sanuki, Naoko AU - Sanuki N FAU - Ishikura, Satoshi AU - Ishikura S FAU - Oku, Yohei AU - Oku Y FAU - Aoki, Yousuke AU - Aoki Y FAU - Kunieda, Etsuo AU - Kunieda E FAU - Shigematsu, Naoyuki AU - Shigematsu N LA - eng PT - Journal Article PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 SB - IM MH - Aged MH - Aged, 80 and over MH - Bronchi/pathology/radiation effects MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery MH - Esophagus/pathology/radiation effects MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/pathology/*surgery MH - Male MH - Mediastinum/pathology/radiation effects MH - Middle Aged MH - *Organs at Risk MH - Radiation Dosage MH - Radiation Injuries/*diagnosis MH - Radiosurgery/*adverse effects MH - Retrospective Studies MH - Risk Factors MH - Time Factors MH - Trachea/pathology/radiation effects EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000260 [doi] AID - 01243894-201409000-00021 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1370-6. doi: 10.1097/JTO.0000000000000260. PMID- 25122431 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 LR - 20150312 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study. PG - 1354-62 LID - 10.1097/JTO.0000000000000264 [doi] AB - INTRODUCTION: The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis. METHODS: Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined. RESULTS: The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The kappa score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. CONCLUSION: The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides. FAU - Thunnissen, Erik AU - Thunnissen E AD - Departments of *Pathology and daggerdaggerdaggerdaggerEpidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands; daggerDepartment of Pathology, Faculty of Medicine, Tsukuba, Japan; double daggerRutgers New Jersey Medical School, Newark, New Jersey; section signDepartment of Pathology, Mount Sinai Medical Center, New York, New York; ||Elisabeth Brambilla, CHU Albert Michallon, Institut de Biologie, Departement d'Anatomie et Cytologie Pathologiques, Grenoble Cedex, France; paragraph signBrigham and Women's Hospital, Boston, Massachusetts; #Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; **Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; daggerdaggerPiedmont Pathology Associates, Hickory, North Carolina, and University of North Carolina, Chapel Hill, North Carolina; double daggerdouble daggerDepartment of Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado; section sign section signDivision of Pathology, The Cancer Institute, Japanese Foundation Cancer Research, Tokyo, Japan; ||Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; paragraph sign paragraph signDepartment of Pathology, CHU A Michallon, INSERM U 823-Institut A Bonniot-University J Fourier, Grenoble, France; ##Department of Pathology, Cancer Center Hospital, Tsukuba, Japan; ***Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan; daggerdaggerdaggerDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; double daggerdouble daggerdouble daggerDepartment of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, and Universita degli Studi of Milan, Milan, Italy; section sign section sign section signInstitut fur Pathologie, Jena, Germany; || || ||Duke University Medical Center, Durham, North Carolina; paragraph sign paragraph sign paragraph signUniversity of Texas MD Anderson Cancer Center, Houston, Texas; ###Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; ****Department of Oncology and Radiothe FAU - Noguchi, Masayuki AU - Noguchi M FAU - Aisner, Seena AU - Aisner S FAU - Beasley, Mary Beth AU - Beasley MB FAU - Brambilla, Elisabeth AU - Brambilla E FAU - Chirieac, Lucian R AU - Chirieac LR FAU - Chung, Jin-Haeng AU - Chung JH FAU - Dacic, Sanja AU - Dacic S FAU - Geisinger, Kim R AU - Geisinger KR FAU - Hirsch, Fred R AU - Hirsch FR FAU - Ishikawa, Yuichi AU - Ishikawa Y FAU - Kerr, Keith M AU - Kerr KM FAU - Lantejoul, Sylvie AU - Lantejoul S FAU - Matsuno, Yoshiro AU - Matsuno Y FAU - Minami, Yuko AU - Minami Y FAU - Moreira, Andre L AU - Moreira AL FAU - Pelosi, Giuseppe AU - Pelosi G FAU - Petersen, Iver AU - Petersen I FAU - Roggli, Victor AU - Roggli V FAU - Travis, William D AU - Travis WD FAU - Wistuba, Ignacio AU - Wistuba I FAU - Yatabe, Yasushi AU - Yatabe Y FAU - Dziadziuszko, Rafal AU - Dziadziuszko R FAU - Witte, Birgit AU - Witte B FAU - Tsao, Ming-Sound AU - Tsao MS FAU - Nicholson, Andrew G AU - Nicholson AG LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Observational Study PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 SB - IM CIN - J Thorac Oncol. 2015 Jan;10(1):e4. PMID: 25654732 CIN - J Thorac Oncol. 2015 Jan;10(1):e3-4. PMID: 25384175 MH - Aged MH - Biopsy, Fine-Needle/*methods MH - Carcinoma, Non-Small-Cell Lung/*pathology/surgery MH - Diagnosis, Differential MH - Female MH - Humans MH - Immunohistochemistry/methods MH - Lung Neoplasms/*pathology/surgery MH - Male MH - Middle Aged MH - Pilot Projects MH - Pneumonectomy MH - Prognosis MH - Reproducibility of Results MH - Retrospective Studies EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000264 [doi] AID - 01243894-201409000-00019 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1354-62. doi: 10.1097/JTO.0000000000000264. PMID- 25122430 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. PG - 1345-53 LID - 10.1097/JTO.0000000000000263 [doi] AB - INTRODUCTION: In the phase IV, open-label, single-arm study NCT01203917, first-line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (previously published). Here, we report EGFR mutation analyses of plasma-derived, circulating-free tumor DNA. METHODS: Mandatory tumor and duplicate plasma (1 and 2) baseline samples were collected (all screened patients; n = 1060). Preplanned, exploratory analyses included EGFR mutation (and subtype) status of tumor versus plasma and between plasma samples. Post hoc, exploratory analyses included efficacy by tumor and plasma EGFR mutation (and subtype) status. RESULTS: Available baseline tumor samples were 1033 of 1060 (118 positive of 859 mutation status known; mutation frequency, 13.7%). Available plasma 1 samples were 803 of 1060 (82 positive of 784 mutation status known; mutation frequency, 10.5%). Mutation status concordance between 652 matched tumor and plasma 1 samples was 94.3% (95% confidence interval [CI], 92.3-96.0) (comparable for mutation subtypes); test sensitivity was 65.7% (95% CI, 55.8-74.7); and test specificity was 99.8% (95% CI, 99.0-100.0). Twelve patients of unknown tumor mutation status were subsequently identified as plasma mutation-positive. Available plasma 2 samples were 803 of 1060 (65 positive of 224 mutation status-evaluable and -known). Mutation status concordance between 224 matched duplicate plasma 1 and 2 samples was 96.9% (95% CI, 93.7-98.7). Objective response rates are as follows: mutation-positive tumor, 70% (95% CI, 60.5-77.7); mutation-positive tumor and plasma 1, 76.9% (95% CI, 65.4-85.5); and mutation-positive tumor and mutation-negative plasma 1, 59.5% (95% CI, 43.5-73.7). Median progression-free survival (months) was 9.7 (95% CI, 8.5-11.0; 61 events) for mutation-positive tumor and 10.2 (95% CI, 8.5-12.5; 36 events) for mutation-positive tumor and plasma 1. CONCLUSION: The high concordance, specificity, and sensitivity demonstrate that EGFR mutation status can be accurately assessed using circulating-free tumor DNA. Although encouraging and suggesting that plasma is a suitable substitute for mutation analysis, tumor tissue should remain the preferred sample type when available. FAU - Douillard, Jean-Yves AU - Douillard JY AD - *Institut de Cancerologie, Centre Rene Gauducheau, Nantes, France; daggerNational Koranyi Institute of Pulmonology, Budapest, Hungary; double daggerHospital Regional Universitario, Malaga, Spain; section signInstitutul Oncologic Prof. Dr. Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania; and ||AstraZeneca, Macclesfield, United Kingdom. FAU - Ostoros, Gyula AU - Ostoros G FAU - Cobo, Manuel AU - Cobo M FAU - Ciuleanu, Tudor AU - Ciuleanu T FAU - Cole, Rebecca AU - Cole R FAU - McWalter, Gael AU - McWalter G FAU - Walker, Jill AU - Walker J FAU - Dearden, Simon AU - Dearden S FAU - Webster, Alan AU - Webster A FAU - Milenkova, Tsveta AU - Milenkova T FAU - McCormack, Rose AU - McCormack R LA - eng SI - ClinicalTrials.gov/NCT00388206 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (DNA, Neoplasm) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - S65743JHBS (gefitinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/metabolism MH - DNA Mutational Analysis MH - DNA, Neoplasm/*genetics/metabolism MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/drug therapy/*genetics/metabolism MH - Male MH - Middle Aged MH - *Mutation MH - Prospective Studies MH - Protein Kinase Inhibitors/therapeutic use MH - Quinazolines/*therapeutic use MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics/metabolism MH - Single-Blind Method MH - Treatment Outcome PMC - PMC4224589 OID - NLM: PMC4224589 EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000263 [doi] AID - 01243894-201409000-00018 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1345-53. doi: 10.1097/JTO.0000000000000263. PMID- 25122429 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Safety and effectiveness of bevacizumab-containing treatment for non-small-cell lung cancer: final results of the ARIES observational cohort study. PG - 1332-9 LID - 10.1097/JTO.0000000000000257 [doi] AB - INTRODUCTION: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. METHODS: From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. RESULTS: ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31-93), and 252 patients (12.8%) identified as never smokers. Median progression-free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first-line bevacizumab plus chemotherapy. Incidences of bevacizumab-associated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. CONCLUSION: Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC. FAU - Lynch, Thomas J Jr AU - Lynch TJ Jr AD - *Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut; daggerSarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, Tennessee; double daggerDepartment of Oncology, Johns Hopkins Medical School, Baltimore, Maryland; section signOncology Associates of Bridgeport, PC, Trumbull, Connecticut; ||Duke University Health Systems, Durham, North Carolina; paragraph signThe University of Miami Sylvester Cancer Center, Deerfield Beach, Florida; #University of Minnesota, Minneapolis, Minnesota; **National Lung Cancer Partnership, Madison, Wisconsin; daggerdaggerKarmanos Cancer Institute, Detroit, Michigan; double daggerdouble daggerGenentech, Inc., South San Francisco, California; and section sign section signScripps Clinic, La Jolla, California. FAU - Spigel, David R AU - Spigel DR FAU - Brahmer, Julie AU - Brahmer J FAU - Fischbach, Neal AU - Fischbach N FAU - Garst, Jennifer AU - Garst J FAU - Jahanzeb, Mohammad AU - Jahanzeb M FAU - Kumar, Priya AU - Kumar P FAU - Vidaver, Regina M AU - Vidaver RM FAU - Wozniak, Antoinette J AU - Wozniak AJ FAU - Fish, Susan AU - Fish S FAU - Flick, E Dawn AU - Flick ED FAU - Leon, Larry AU - Leon L FAU - Hazard, Sebastien J AU - Hazard SJ FAU - Kosty, Michael P AU - Kosty MP CN - ARIES Study Investigators LA - eng SI - ClinicalTrials.gov/NCT00388206 PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Vascular Endothelial Growth Factor A) RN - 2S9ZZM9Q9V (bevacizumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Angiogenesis Inhibitors/therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology MH - Disease-Free Survival MH - Drug Therapy, Combination MH - Europe/epidemiology MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/pathology MH - Male MH - Middle Aged MH - Prospective Studies MH - Survival Rate/trends MH - Time Factors MH - Treatment Outcome MH - United States/epidemiology MH - Vascular Endothelial Growth Factor A EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 AID - 10.1097/JTO.0000000000000257 [doi] AID - 01243894-201409000-00016 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1332-9. doi: 10.1097/JTO.0000000000000257. PMID- 25122425 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - The prognostic significance of focal adhesion kinase expression in stage I non-small-cell lung cancer. PG - 1278-84 LID - 10.1097/JTO.0000000000000248 [doi] AB - INTRODUCTION: Focal adhesion kinase (FAK) plays a significant role in cancer cell survival signaling and is overexpressed in various malignancies, including lung cancer. Previous studies suggest that FAK overexpression is an independent factor predicting poor prognosis in non-small-cell lung cancer (NSCLC). The aim of this study is to confirm these findings specifically in stage I NSCLC. METHODS: A retrospective tissue microarray (TMA) analysis of FAK protein expression by immunohistochemistry was performed in 157 surgically resected stage I NSCLC specimen and in the corresponding matched normal lung tissue. The FAK 4.47 monoclonal antibody was used for FAK immunostaining. The scoring system of triplicate tumor cores included intensity of staining plus extent of staining for a composite score that ranged from 0 to 6. The association between FAK score and survival was evaluated. RESULTS: There were 103 stage IA and 54 stage IB patients, with mean follow-up of 5.5 years. Normal lung alveoli and interstitial tissue had mean FAK score of 0 (median score 0, range 0 to 2). Tumor samples had mean FAK score 3.1 (median score 3.5, range 0-6), with 57% of the samples having FAK score >/= 3. Continuous FAK score was not associated with demographic data, tumor histology, or grade, nor survival in this cohort of stage I NSCLC patients. CONCLUSIONS: FAK is expressed in more than 50% of stage I NSCLC lung cancer but not in normal lung alveoli and interstitial tissue. FAK expression is not associated with survival outcome in this North American cohort. FAU - Dy, Grace K AU - Dy GK AD - *Department of Medicine; daggerDepartment of Pathology; double daggerDepartment of Biostatistics; and section signDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY. FAU - Ylagan, Lourdes AU - Ylagan L FAU - Pokharel, Saraswati AU - Pokharel S FAU - Miller, Austin AU - Miller A FAU - Brese, Elizabeth AU - Brese E FAU - Bshara, Wiam AU - Bshara W FAU - Morrison, Carl AU - Morrison C FAU - Cance, William G AU - Cance WG FAU - Golubovskaya, Vita M AU - Golubovskaya VM LA - eng GR - CA65910/CA/NCI NIH HHS/United States GR - R01 CA065910/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Tumor Markers, Biological) RN - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathology MH - Focal Adhesion Protein-Tyrosine Kinases/biosynthesis/*genetics MH - Follow-Up Studies MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/*genetics/metabolism/pathology MH - Male MH - Middle Aged MH - *Neoplasm Staging MH - Prognosis MH - Retrospective Studies MH - Time Factors MH - Tissue Array Analysis MH - Tumor Markers, Biological/genetics PMC - PMC4133746 MID - NIHMS595569 OID - NLM: NIHMS595569 [Available on 09/01/15] OID - NLM: PMC4133746 [Available on 09/01/15] EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 PMCR- 2015/09/01 00:00 AID - 10.1097/JTO.0000000000000248 [doi] AID - 01243894-201409000-00010 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1278-84. doi: 10.1097/JTO.0000000000000248. PMID- 25122424 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage I to IIIA non-small-cell lung cancers. PG - 1272-7 LID - 10.1097/JTO.0000000000000256 [doi] AB - INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. FAU - Drilon, Alexander AU - Drilon A AD - *Memorial Sloan Kettering Cancer Center, New York, NY; daggerTokyo Medical and Dental University, Tokyo, Japan; and double daggerMassachusetts General Hospital Cancer Center, Boston, MA. FAU - Sugita, Hirofumi AU - Sugita H FAU - Sima, Camelia S AU - Sima CS FAU - Zauderer, Marjorie AU - Zauderer M FAU - Rudin, Charles M AU - Rudin CM FAU - Kris, Mark G AU - Kris MG FAU - Rusch, Valerie W AU - Rusch VW FAU - Azzoli, Christopher G AU - Azzoli CG LA - eng GR - R01 CA092315/CA/NCI NIH HHS/United States GR - R01CA092315/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (DNA, Neoplasm) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics/surgery MH - DNA Methylation MH - DNA, Neoplasm/*genetics MH - Female MH - Follow-Up Studies MH - *Genes, Tumor Suppressor MH - Humans MH - Lung Neoplasms/diagnosis/*genetics/surgery MH - Male MH - Middle Aged MH - *Neoplasm Staging MH - Pneumonectomy/*methods MH - Prognosis MH - Promoter Regions, Genetic MH - Prospective Studies MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors PMC - PMC4133740 MID - NIHMS597315 OID - NLM: NIHMS597315 [Available on 09/01/15] OID - NLM: PMC4133740 [Available on 09/01/15] EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 PMCR- 2015/09/01 00:00 AID - 10.1097/JTO.0000000000000256 [doi] AID - 01243894-201409000-00009 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1272-7. doi: 10.1097/JTO.0000000000000256. PMID- 25122423 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 LR - 20150508 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Inherited variation in the ATP-binding cassette transporter ABCB1 and survival after chemotherapy for stage III-IV lung cancer. PG - 1264-71 LID - 10.1097/JTO.0000000000000262 [doi] AB - BACKGROUND: The ATP-binding cassette transporter gene ABCB1 and the glutathione S-transferase gene GSTP1 code for a multidrug resistance protein and for a detoxifying phase II metabolic enzyme, respectively, with substrate specificities that include chemotherapy drugs often used to treat lung cancer. METHODS: We genotyped 11 ABCB1 and eight GSTP1 single nucleotide polymorphisms (SNPs) in 698 white lung cancer patients (all current or former cigarette smokers) and used log-rank test statistics and proportional hazards regression to evaluate associations between SNP genotype and survival. RESULTS: Using data from all 698 cases, one SNP in ABCB1 (rs2235013) was statistically significantly associated with overall survival (p = 0.038, log-rank test). Chemotherapy and stage jointly (p = 0.025) significantly modified the association between rs2235013 and survival, with statistically significant (p = 0.013, log-rank test) association observed in the subgroup of stage III to IV lung cancer patients who received chemotherapy as part of their first course of treatment (n = 160; 93.1% nonsmall cell). Patients who inherited the minor T allele at ABCB1 rs2235013 experienced better overall survival and recurrence-free survival (hazard ratio, per minor T allele, [95% confidence interval]: 0.66 [0.49-0.90] and 0.55 [0.31-0.95], respectively; adjusted for year of diagnosis, sex, age at diagnosis, cigarette pack years, and stage). In addition, in the advanced stage chemotherapy-treated subgroup, four ABCB1 SNPs (rs6949448, rs2235046, rs1128503, and rs10276036) in mutual high linkage disequilibrium with rs2235013 and an independent ABCB1 SNP (rs1045642) showed statistically significant association (p < 0.05) with survival. CONCLUSIONS: Inherited variation in ABCB1 may affect survival specifically in advanced stage lung cancer patients who receive chemotherapy. FAU - Weissfeld, Joel L AU - Weissfeld JL AD - *University of Pittsburgh Cancer Institute and daggerDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health; double daggerDivision of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine; section signDepartment of Medicine, University of Pittsburgh School of Medicine; ||Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine; paragraph signDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA. FAU - Diergaarde, Brenda AU - Diergaarde B FAU - Nukui, Tomoko AU - Nukui T FAU - Buch, Shama AU - Buch S FAU - Pennathur, Arjun AU - Pennathur A FAU - Socinski, Mark A AU - Socinski MA FAU - Siegfried, Jill M AU - Siegfried JM FAU - Romkes, Marjorie AU - Romkes M LA - eng GR - 2P30 CA047904/CA/NCI NIH HHS/United States GR - 5P50 CA090440/CA/NCI NIH HHS/United States GR - P30 CA047904/CA/NCI NIH HHS/United States GR - P30CA047904/CA/NCI NIH HHS/United States GR - P50 CA090440/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (ABCB1 protein, human) RN - 0 (Antineoplastic Agents) RN - 0 (DNA, Neoplasm) RN - 0 (P-Glycoproteins) SB - IM MH - Aged MH - Aged, 80 and over MH - Alleles MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/diagnosis/drug therapy/*genetics MH - DNA, Neoplasm/*genetics MH - Female MH - Follow-Up Studies MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Lung Neoplasms/drug therapy/*genetics/mortality MH - Male MH - Middle Aged MH - *Neoplasm Staging MH - P-Glycoproteins/genetics/metabolism MH - Pennsylvania/epidemiology MH - *Polymorphism, Genetic MH - Retrospective Studies MH - Survival Rate/trends PMC - PMC4134100 MID - NIHMS599136 OID - NLM: NIHMS599136 [Available on 09/01/15] OID - NLM: PMC4134100 [Available on 09/01/15] EDAT- 2014/08/15 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/08/15 06:00 PMCR- 2015/09/01 00:00 AID - 10.1097/JTO.0000000000000262 [doi] AID - 01243894-201409000-00008 [pii] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1264-71. doi: 10.1097/JTO.0000000000000262. PMID- 25120814 OWN - NLM STAT- MEDLINE DA - 20140814 DCOM- 20150514 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 7 IP - 7 DP - 2014 TI - A comparison of ARMS and mutation specific IHC for common activating EGFR mutations analysis in small biopsy and cytology specimens of advanced non small cell lung cancer. PG - 4310-6 AB - We have compared mutation analysis by Amplification Refractory Mutation System (ARMS) and epidermal growth factor receptor (EGFR) mutant-specific antibodies for their ability to detect two common activating EGFR mutations in a cohort of 115 advanced non-small cell lung cancer (NSCLC), including cytology material, core biopsy, and bronchoscopic biopsies. Assessment of EGFR mutation status was performed by using antibodies and ARMS assay specific to the two major forms of mutant EGFR, exon 19 deletion E746-A750 (c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750 del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg). In this study the optimal buffer for antigen retrieval was sodium citrate (pH 6.0). Q score was used to evaluate the specific mutant EGFR proteins expression. Validation using clinical material showed deletions in exon 19 were detected in 19.1% and L858R mutation in 20% of all cases by ARMS assay. A cutoff value of score 1 was used as positive by IHC. No wild type cases were immuno-reactive. The antibodies performed well in cytology, core biopsies and bronchoscopic biopsies. There were only one false positive case using L858R IHC (sensitivity 100%, specificity 98.5%, positive predictive value 96%, negative predictive value 100%). All 23 E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 100%, positive predictive value 100% and negative predictive value 100%. The result of the IHC stains was finely correlated with mutations status determined by ARMS assay. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases especially where limited tumor material is available, or in situations where molecular genetic analysis is not readily available. FAU - Wang, Xueqing AU - Wang X AD - Department of Pathology, Southeast University, Zhongda Hospital Nanjing 210009, P.R. China. FAU - Wang, Guoqing AU - Wang G AD - Department of Pathology, Southeast University, Zhongda Hospital Nanjing 210009, P.R. China. FAU - Hao, Yueyue AU - Hao Y AD - Department of Pathology, Southeast University, Zhongda Hospital Nanjing 210009, P.R. China. FAU - Xu, Yinhong AU - Xu Y AD - Department of Pathology, Southeast University, Zhongda Hospital Nanjing 210009, P.R. China. FAU - Zhang, Lihua AU - Zhang L AD - Department of Pathology, Southeast University, Zhongda Hospital Nanjing 210009, P.R. China. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140615 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Antibodies, Monoclonal) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Aged MH - Antibodies, Monoclonal/*diagnostic use MH - Biopsy MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Cytological Techniques MH - DNA Mutational Analysis/*methods MH - Female MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/*genetics MH - Male MH - Middle Aged MH - Mutation MH - Receptor, Epidermal Growth Factor/*genetics MH - Sensitivity and Specificity PMC - PMC4129049 OID - NLM: PMC4129049 OTO - NOTNLM OT - EGFR mutation OT - NSCLC OT - cytology OT - immunohistochemistry EDAT- 2014/08/15 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/15 06:00 PHST- 2014 [ecollection] PHST- 2014/05/19 [received] PHST- 2014/06/03 [accepted] PHST- 2014/06/15 [epublish] PST - epublish SO - Int J Clin Exp Pathol. 2014 Jun 15;7(7):4310-6. eCollection 2014. PMID- 25120740 OWN - NLM STAT- MEDLINE DA - 20140814 DCOM- 20150514 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 7 IP - 7 DP - 2014 TI - Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review. PG - 3632-46 AB - BACKGROUND: CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. METHODS: Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. RESULTS: We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. CONCLUSION: Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker. FAU - Luo, Zhuang AU - Luo Z AD - Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University Kunming, Yunnan, China. FAU - Wu, Rong-Rong AU - Wu RR AD - Department of Radiology, The First People's Hospital of Yunnan Province Affiliated to Kunming University of Science and Technology Kunming, Yunnan, China ; Kunming Medical University Kunming, Yunnan, China. FAU - Lv, Liang AU - Lv L AD - Department of Radiology, The First People's Hospital of Yunnan Province Affiliated to Kunming University of Science and Technology Kunming, Yunnan, China. FAU - Li, Peng AU - Li P AD - Department of Radiology, The First People's Hospital of Yunnan Province Affiliated to Kunming University of Science and Technology Kunming, Yunnan, China. FAU - Zhang, Li-Yan AU - Zhang LY AD - Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University Kunming, Yunnan, China. FAU - Hao, Qing-Lin AU - Hao QL AD - Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University Kunming, Yunnan, China. FAU - Li, Wei AU - Li W AD - Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University Kunming, Yunnan, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20140615 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Antigens, CD44) RN - 0 (CD44 protein, human) RN - 0 (Tumor Markers, Biological) SB - IM MH - Antigens, CD44/*biosynthesis MH - Carcinoma, Non-Small-Cell Lung/metabolism/mortality/*pathology MH - Humans MH - Lung Neoplasms/metabolism/mortality/*pathology MH - Prognosis MH - Tumor Markers, Biological/*analysis PMC - PMC4128975 OID - NLM: PMC4128975 OTO - NOTNLM OT - CD44 OT - CD44-V6 OT - Non-small cell lung cancer (NSCLC) OT - clinicopathological features OT - meta-analysis OT - overall survival OT - panCD44 EDAT- 2014/08/15 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/08/15 06:00 PHST- 2014 [ecollection] PHST- 2014/04/21 [received] PHST- 2014/06/23 [accepted] PHST- 2014/06/15 [epublish] PST - epublish SO - Int J Clin Exp Pathol. 2014 Jun 15;7(7):3632-46. eCollection 2014. PMID- 25114510 OWN - NLM STAT- MEDLINE DA - 20140812 DCOM- 20150511 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 8 DP - 2014 TI - Clinical utility of erlotinib for the treatment of non-small-cell lung cancer in Japanese patients: current evidence. PG - 1037-46 LID - 10.2147/DDDT.S50358 [doi] AB - Gefitinib, an epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI), has been approved in Japan for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) based on Phase II clinical trials since 2002. Erlotinib, another EGFR-TKI, was also approved a few years thereafter. In 2004, activating mutations in the EGFR gene were discovered to be a predictive biomarker for EGFR-TKI treatment, and gefitinib, which is not effective for patients with EGFR wild-type NSCLC, has since been used only in patients with EGFR-mutated NSCLC. In contrast, erlotinib is potentially effective for the treatment of EGFR wild-type NSCLC. Similar to gefitinib, erlotinib is also effective for EGFR-mutated NSCLC and has been used as an initial treatment for patients with advanced EGFR-mutated NSCLC. Both gefitinib and erlotinib can be used in a Japanese clinical setting. The approved daily dose of erlotinib (150 mg) is equal to the maximum tolerated dose of erlotinib. In contrast, the daily dose of gefitinib has been set at 250 mg, which is approximately one-third of the maximum tolerated dose of gefitinib. Accordingly, a higher serum concentration can be achieved using erlotinib, compared with gefitinib. This advantage can be applied to the treatment of central nervous system metastases (brain metastasis and carcinomatous meningitis), the treatment of which is complicated by the difficulty drugs have penetrating the blood-brain barrier. Although patients with EGFR-mutated NSCLC respond dramatically to EGFR-TKIs, some patients have a poor response and the majority eventually undergo disease progression. To overcome such resistance, several novel treatment strategies, such as combination therapy and next-generation EGFR-TKIs, have been attempted. FAU - Togashi, Yosuke AU - Togashi Y AD - Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan. FAU - Hayashi, Hidetoshi AU - Hayashi H AD - Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan ; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan ; Department of Medical Oncology, Kishiwada Municipal Hospital, Osaka, Japan. FAU - Nakagawa, Kazuhiko AU - Nakagawa K AD - Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan. FAU - Nishio, Kazuto AU - Nishio K AD - Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20140731 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) RN - S65743JHBS (gefitinib) SB - IM MH - Asian Continental Ancestry Group MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Dose-Response Relationship, Drug MH - Humans MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Maximum Tolerated Dose MH - Protein Kinase Inhibitors/adverse effects/pharmacology/therapeutic use MH - Quinazolines/adverse effects/pharmacology/*therapeutic use MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics PMC - PMC4124069 OID - NLM: PMC4124069 OTO - NOTNLM OT - EGFR mutation OT - epidermal growth factor receptor tyrosine kinase inhibitor OT - erlotinib OT - non-small-cell lung cancer EDAT- 2014/08/13 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/13 06:00 PHST- 2014 [ecollection] PHST- 2014/07/31 [epublish] AID - 10.2147/DDDT.S50358 [doi] AID - dddt-8-1037 [pii] PST - epublish SO - Drug Des Devel Ther. 2014 Jul 31;8:1037-46. doi: 10.2147/DDDT.S50358. eCollection 2014. PMID- 25108807 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150522 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 112 IP - 2 DP - 2014 Aug TI - Stereotactic ablative radiotherapy (SABR) using 70 Gy in 10 fractions for non-small cell lung cancer: exploration of clinical indications. PG - 256-61 LID - 10.1016/j.radonc.2014.07.010 [doi] LID - S0167-8140(14)00305-3 [pii] AB - BACKGROUND AND PURPOSE: We report our outcomes for patients with NSCLC treated with SABR to 70 Gy in 10 fractions and propose indications for this regimen as well as new dose-volume constraints. MATERIALS AND METHODS: Volumetric image-guided SABR was used to treat 82 patients with clinical challenging NSCLC, not suitable for 50 Gy in 4 fractions, to a final dose of 70 Gy in 10 fractions. Endpoints included overall survival (OS), toxicity, and disease control. RESULTS: At a median follow-up time of 21.1 months, 2-year OS and local control rates were 66.9% and 96.2%, respectively. The most common side effects were radiation pneumonitis (14.6% grade 2, 2.4% grade 3), followed by chest wall pain (4.9% grade 2, 1.2% grade 3). Multivariate analysis revealed chest wall V50>60 cm(3) to be associated with chest wall pain. No patient developed brachial plexopathy. One patient with bronchial tree tumor invasion died of hemoptysis. CONCLUSIONS: SABR with 70 Gy in 10 fractions appears to achieve excellent local control and acceptable toxicity for clinically challenging cases with improved tolerance of the chest wall and brachial plexus as compared with 50 Gy in 4 fractions. This regimen may not be suitable in patients with tumor invading critical central structures. More studies are needed to validate our conclusions. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Li, Qiaoqiao AU - Li Q AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Swanick, Cameron W AU - Swanick CW AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Allen, Pamela K AU - Allen PK AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Gomez, Daniel R AU - Gomez DR AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Welsh, James W AU - Welsh JW AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Liao, Zhongxing AU - Liao Z AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Balter, Peter A AU - Balter PA AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. FAU - Chang, Joe Y AU - Chang JY AD - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. Electronic address: jychang@mdanderson.org. LA - eng PT - Journal Article DEP - 20140806 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery MH - Dose Fractionation MH - Female MH - Humans MH - Lung Neoplasms/pathology/*surgery MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Radiation Pneumonitis/etiology MH - Radiosurgery/adverse effects/*methods MH - Surgery, Computer-Assisted MH - Survival Rate MH - Treatment Outcome OTO - NOTNLM OT - Central lesion OT - Hypofractionation OT - NSCLC OT - SABR OT - SBRT EDAT- 2014/08/12 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/08/11 06:00 PHST- 2014/04/29 [received] PHST- 2014/07/11 [revised] PHST- 2014/07/13 [accepted] PHST- 2014/08/06 [aheadofprint] AID - S0167-8140(14)00305-3 [pii] AID - 10.1016/j.radonc.2014.07.010 [doi] PST - ppublish SO - Radiother Oncol. 2014 Aug;112(2):256-61. doi: 10.1016/j.radonc.2014.07.010. Epub 2014 Aug 6. PMID- 25107554 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150522 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 112 IP - 2 DP - 2014 Aug TI - Dose-volume-response analysis in stereotactic radiotherapy for early lung cancer. PG - 262-6 LID - 10.1016/j.radonc.2014.07.004 [doi] LID - S0167-8140(14)00290-4 [pii] AB - BACKGROUND AND PURPOSE: Japanese and Western approaches to stereotactic ablative radiotherapy (SABR) are considerably different, particularly with respect to dose prescription and reporting, which makes comparisons of Japanese versus European or American results challenging. Using individual patient data, the aim of this study was to analyze the dose-local-control relationship and its impact on survival. MATERIAL AND METHODS: Patients receiving SABR for single-lesion early stage NSCLC in Osaka (OM) or Groningen (GN) were analyzed. Doses were recalculated using state-of-the-art dose calculation algorithms and expressed as biologically effective dose (BED) at PTV margin. Survival, local control (LC), and effect of treatment failure in operable and inoperable patients on survival were analyzed. RESULTS: Between 2006 and 2010, 383 patients were included. The BED at PTV periphery was 102 Gy(1)(0) (+/-21) in GN and 83 Gy(1)(0) (+/-5) in OM. Unadjusted overall survival (OS) was better in OM (72% vs 52%; p<0.001), but GTVs and performance status (PS) were also significantly more favorable in OM. Adjusted for GTV and PS, OS was not different between institutions (HR 0.88; p=0.47). LC was better in GN (93% vs 84%; p<0.05). Local control predicted survival in operable patients: Adjusted for GTV and PS, the HR of local failure for OS was 7.5 (2-27; p=0.003) for operable, and 1.1 (0.7-1.9; p=0.6) for inoperable patients. CONCLUSIONS: Sufficient dose is crucial for local control, which was a significant factor for survival for operable patients. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Suzuki, Osamu AU - Suzuki O AD - Department of Radiation Oncology, Osaka University, Graduate School of Medicine, Japan. Electronic address: osamu-s@umin.ac.jp. FAU - Mitsuyoshi, Takamasa AU - Mitsuyoshi T AD - Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. FAU - Miyazaki, Masayoshi AU - Miyazaki M AD - Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. FAU - Teshima, Teruki AU - Teshima T AD - Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. FAU - Nishiyama, Kinji AU - Nishiyama K AD - Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. FAU - Ubbels, Jan F AU - Ubbels JF AD - Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Netherlands. FAU - Bolt, Rene A AU - Bolt RA AD - Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Netherlands. FAU - Langendijk, Johannes A AU - Langendijk JA AD - Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Netherlands. FAU - Widder, Joachim AU - Widder J AD - Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Netherlands. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140805 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 SB - IM MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery MH - Cohort Studies MH - Dose-Response Relationship, Radiation MH - Female MH - Humans MH - Japan MH - Lung Neoplasms/pathology/*surgery MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Netherlands MH - Radiosurgery/*methods MH - Survival Rate OTO - NOTNLM OT - BED OT - Operable OT - Stereotactic radiotherapy OT - Survival EDAT- 2014/08/12 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/08/10 06:00 PHST- 2013/11/17 [received] PHST- 2014/06/24 [revised] PHST- 2014/07/10 [accepted] PHST- 2014/08/05 [aheadofprint] AID - S0167-8140(14)00290-4 [pii] AID - 10.1016/j.radonc.2014.07.004 [doi] PST - ppublish SO - Radiother Oncol. 2014 Aug;112(2):262-6. doi: 10.1016/j.radonc.2014.07.004. Epub 2014 Aug 5. PMID- 25088661 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials. PG - 408-14 LID - 10.1016/j.lungcan.2014.07.005 [doi] LID - S0169-5002(14)00305-5 [pii] AB - OBJECTIVES: Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. METHODS: Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. RESULTS: Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. CONCLUSIONS: The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens. CI - Copyright (c) 2014. Published by Elsevier Ireland Ltd. FAU - Scagliotti, G V AU - Scagliotti GV AD - University of Torino at S. Luigi Hospital, Orbassano, Torino, Italy. FAU - Gridelli, C AU - Gridelli C AD - S. Giuseppe Moscati Hospital, Avellino, Italy. FAU - de Marinis, F AU - de Marinis F AD - European Institute of Oncology, Thoracic Oncology Division, Milan, Italy. FAU - Thomas, M AU - Thomas M AD - Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitatsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Germany. FAU - Dediu, M AU - Dediu M AD - Institute of Oncology Bucharest, Bucharest, Romania. FAU - Pujol, J-L AU - Pujol JL AD - Montpellier Academic Hospital, Montpellier, France. FAU - Manegold, C AU - Manegold C AD - Heidelberg University Medical Center, Mannheim, Germany. FAU - San Antonio, B AU - San Antonio B AD - Eli Lilly and Company, Madrid, Spain. FAU - Peterson, P M AU - Peterson PM AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - John, W AU - John W AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Chouaki, N AU - Chouaki N AD - Eli Lilly and Company, Suresnes, Hauts de Seine, France. FAU - Visseren-Grul, C AU - Visseren-Grul C AD - Eli Lilly and Company, Houten, The Netherlands. FAU - Paz-Ares, L G AU - Paz-Ares LG AD - Instituto de Biomedicina de Sevilla (University Hospital Virgen del Rocio, CSIC and Seville University), Seville, Spain. Electronic address: lpazares@hotmail.com. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140716 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*pathology MH - Cisplatin/administration & dosage MH - Female MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Humans MH - Induction Chemotherapy MH - Lung Neoplasms/*drug therapy/mortality/*pathology MH - Maintenance Chemotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - Carcinoma OT - Cisplatin OT - Induction chemotherapy OT - Maintenance chemotherapy OT - Non-small cell lung OT - Nonsquamous OT - Pemetrexed OT - Phase III clinical trial EDAT- 2014/08/05 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/05 06:00 PHST- 2014/04/15 [received] PHST- 2014/07/01 [revised] PHST- 2014/07/07 [accepted] PHST- 2014/07/16 [aheadofprint] AID - S0169-5002(14)00305-5 [pii] AID - 10.1016/j.lungcan.2014.07.005 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):408-14. doi: 10.1016/j.lungcan.2014.07.005. Epub 2014 Jul 16. PMID- 25082565 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study. PG - 415-9 LID - 10.1016/j.lungcan.2014.07.006 [doi] LID - S0169-5002(14)00306-7 [pii] AB - BACKGROUND: Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. OBJECTIVE: To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. METHODS: In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. RESULTS: 147 patients were randomized (median age: 60+/-8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. CONCLUSION: Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Auliac, J B AU - Auliac JB AD - Department of Pneumology, Quesnay Hospital, Mantes La Jolie, France. Electronic address: jb.auliac@ch-mantes-la-jolie.fr. FAU - Chouaid, C AU - Chouaid C AD - Department of Pneumology, Saint Antoine Hospital, Paris, France. FAU - Greiller, L AU - Greiller L AD - Multidisciplinary Oncology and Therapeutic Innovations, AP-HM, Marseilles, France. FAU - Monnet, I AU - Monnet I AD - Service de pneumologie, CHI, Creteil, France. FAU - Le Caer, H AU - Le Caer H AD - CH de Draguignan, Draguignan, France. FAU - Falchero, L AU - Falchero L AD - CH Villefranche Sur Saone, Villefranche-sur-Saone, France. FAU - Corre, R AU - Corre R AD - Pneumology, CHU Pontchaillou, Rennes, France. FAU - Descourt, R AU - Descourt R AD - CHU Morvan, Brest, France. FAU - Bota, S AU - Bota S AD - Hopital Charles Nicolle, Rouen, France. FAU - Berard, H AU - Berard H AD - Pneumology, HIA, Toulon, France. FAU - Schott, R AU - Schott R AD - Centre Paul Strauss, Strasbourg, France. FAU - Bizieux, A AU - Bizieux A AD - CHD La Roche Sur Yon, La Roche Sur Yon, France. FAU - Fournel, P AU - Fournel P AD - Institut de Cancerologie de la Loire, Saint Priest En Jarez, France. FAU - Labrunie, A AU - Labrunie A AD - CEBIMER, CHU limoges, Limoges, France. FAU - Marin, B AU - Marin B AD - CEBIMER, CHU limoges, Limoges, France. FAU - Vergnenegre, A AU - Vergnenegre A AD - CHU Limoges, Limoges, France. CN - GFPC team LA - eng PT - Controlled Clinical Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140717 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Quinazolines) RN - 0 (Taxoids) RN - 15H5577CQD (docetaxel) RN - J4T82NDH7E (erlotinib) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/pathology MH - Male MH - Middle Aged MH - Quinazolines/administration & dosage MH - Retreatment MH - Risk Factors MH - Taxoids/administration & dosage MH - Treatment Failure MH - Treatment Outcome OTO - NOTNLM OT - Docetaxel OT - Epithelial growth factor wild-type status OT - Erlotinib OT - Non-small-cell lung cancer OT - Second-line EDAT- 2014/08/02 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/02 06:00 PHST- 2014/04/11 [received] PHST- 2014/07/07 [revised] PHST- 2014/07/10 [accepted] PHST- 2014/07/17 [aheadofprint] AID - S0169-5002(14)00306-7 [pii] AID - 10.1016/j.lungcan.2014.07.006 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):415-9. doi: 10.1016/j.lungcan.2014.07.006. Epub 2014 Jul 17. PMID- 25082564 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer. PG - 401-7 LID - 10.1016/j.lungcan.2014.07.007 [doi] LID - S0169-5002(14)00307-9 [pii] AB - OBJECTIVES: Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB. MATERIALS AND METHODS: Chinese patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned (1:1) to 6 cycles maximum (21 days/cycle) of pemetrexed 500mg/m(2)+cisplatin 75mg/m(2) (day 1), or gemcitabine 1250mg/m(2) (days 1 and 8)+cisplatin 75mg/m(2) (day 1). RESULTS: In JMIL, 256 Chinese patients were randomized (PC, n=126; GC, n=130). Patient baseline characteristics were balanced between treatment arms. In the combined dataset, PC was superior to GC in prolonging OS, with adjusted hazard ratio (HR) of 0.87 (95% CI: 0.77-0.98, p=0.023) and median OS of 11.76 versus 10.94 months. In the JMIL-only population, no significant OS difference observed between treatment arms (adjusted HR=1.03 [95% CI: 0.77-1.39, p=0.822]; unadjusted HR=0.996 [95% CI: 0.74-1.33, p=0.980]), nor for other secondary efficacy endpoints. Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities, 54 (43.2%) versus 71 (55.9%) for GC (p=0.045), with significantly lower rates of leukocytopenia, thrombocytopenia, and fatigue. CONCLUSION: This study showed that in the combined population, OS of PC was superior to GC, while in the Chinese-only population, no significant difference was observed; a better safety and risk/benefit profile was found in the PC arm. A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLC patients in a first-line setting. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangdong, China. Electronic address: syylwu@live.cn. FAU - Lu, Shun AU - Lu S AD - Lung Cancer Center, Shanghai Chest Hospital, affiliated to Shanghai JiaoTong University, Shanghai, China. FAU - Cheng, Ying AU - Cheng Y AD - Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China. FAU - Zhou, Caicun AU - Zhou C AD - Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Affiliated Cancer Institute, Shanghai, China. FAU - Wang, Mengzhao AU - Wang M AD - Department of Oncology, Peking Union Medical College Hospital, Beijing, China. FAU - Qin, Shukui AU - Qin S AD - Department of Oncology, 81st Hospital of the Chinese PLA, Nanjing, China. FAU - Lu, You AU - Lu Y AD - Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, China. FAU - Zhu, Yunzhong AU - Zhu Y AD - Department of Chest Tumor, Beijing Chest Hospital, affiliated to Capital Medical University, Beijing, China. FAU - Song, Xiangqun AU - Song X AD - Cancer Hospital affiliated to Guangxi Medical University, Nanning, China. FAU - Wang, Xin AU - Wang X AD - Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Center, Shanghai, China. FAU - Barraclough, Helen AU - Barraclough H AD - Asia Pacific Statistical Sciences, Eli Lilly Australia, Sydney, Australia. FAU - Zhang, Xiaoqing AU - Zhang X AD - Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China. FAU - Chi, Haidong AU - Chi H AD - Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China. FAU - Orlando, Mauro AU - Orlando M AD - Oncology Emerging Markets, Eli Lilly Interamerica Inc., Buenos Aires, Argentina. LA - eng SI - ClinicalTrials.gov/NCT00087711 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140717 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 0W860991D6 (Deoxycytidine) RN - 5Z93L87A1R (Guanine) RN - B76N6SBZ8R (gemcitabine) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*pathology MH - Cisplatin/administration & dosage MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Female MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/*pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - Chinese OT - Cisplatin OT - First-line chemotherapy OT - Gemcitabine OT - Non-small cell lung cancer OT - Nonsquamous OT - Pemetrexed EDAT- 2014/08/02 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/02 06:00 PHST- 2013/12/29 [received] PHST- 2014/07/08 [revised] PHST- 2014/07/10 [accepted] PHST- 2014/07/17 [aheadofprint] AID - S0169-5002(14)00307-9 [pii] AID - 10.1016/j.lungcan.2014.07.007 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):401-7. doi: 10.1016/j.lungcan.2014.07.007. Epub 2014 Jul 17. PMID- 25074845 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - Tumor response assessment by measuring the single largest lesion per organ in patients with advanced non-small cell lung cancer. PG - 385-9 LID - 10.1016/j.lungcan.2014.07.008 [doi] LID - S0169-5002(14)00308-0 [pii] AB - BACKGROUND: The criterion of two target lesions per organ in the RECIST 1.1 is an arbitrary one, not being supported by any objective evidence. We compared tumor responses, respectively, using the RECIST 1.1 (measuring two target lesions per organ) and modified RECIST 1.1 (measuring the single largest lesion in each organ) in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed medical records of patients with advanced NSCLC who received a first-line chemotherapy between January 2004 and December 2013 and compared tumor responses according to the two criteria using computed tomography. RESULTS: A total of 64 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in the study. The differences in the percentage changes of the sum of tumor measurements between the RECIST 1.1 and mRECIST 1.1 were all within 10%. Thirty-three patients (51.6%) showed an increase in the absolute value of the percentage change when adopting the mRECIST 1.1, instead of the RECIST 1.1. The tumor responses showed high concordance between the two criteria (k=0.899). Only three patients (4.7%) showed disagreement of the responses between the RECIST 1.1 and mRECIST 1.1. The overall response rates (20.3% vs. 20.3%) and disease control rates (89.1% vs. 90.6%) of first-line chemotherapy were not significantly different between the two criteria. CONCLUSION: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the response assessment of patients with advanced NSCLC. Our result suggests that it may be possible to measure the single largest target lesion per organ for evaluation of the best tumor response. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Kim, Hyeong Su AU - Kim HS AD - Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 150-950, Republic of Korea. FAU - Kim, Jung Han AU - Kim JH AD - Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 150-950, Republic of Korea. Electronic address: harricil@hotmail.com. FAU - Yang, Ik AU - Yang I AD - Department of Radiology, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 150-950, Republic of Korea. LA - eng PT - Journal Article DEP - 20140717 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols MH - Carcinoma, Non-Small-Cell Lung/diagnosis/drug therapy/*pathology MH - Female MH - Humans MH - Lung Neoplasms/diagnosis/drug therapy/*pathology MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Tomography, X-Ray Computed MH - Treatment Outcome MH - Tumor Burden OTO - NOTNLM OT - Lung cancer OT - Modified RECIST 1.1 OT - RECIST 1.1 OT - Target lesion OT - Tumor measurement OT - Tumor response EDAT- 2014/07/31 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/07/31 06:00 PHST- 2014/05/20 [received] PHST- 2014/07/07 [revised] PHST- 2014/07/10 [accepted] PHST- 2014/07/17 [aheadofprint] AID - S0169-5002(14)00308-0 [pii] AID - 10.1016/j.lungcan.2014.07.008 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):385-9. doi: 10.1016/j.lungcan.2014.07.008. Epub 2014 Jul 17. PMID- 25064471 OWN - NLM STAT- MEDLINE DA - 20141203 DCOM- 20150522 LR - 20141204 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 112 IP - 2 DP - 2014 Aug TI - Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors. PG - 267-71 LID - 10.1016/j.radonc.2014.07.001 [doi] LID - S0167-8140(14)00287-4 [pii] AB - BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) to central lung tumors can cause esophageal toxicity, but little is known about the incidence or risk factors. We reviewed central lung SBRT patients to identify dosimetric factors predictive of esophageal toxicity. MATERIALS AND METHODS: We assessed esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with alpha/beta=10 Gy (BED(1)(0)), dose-volume histogram variables for the esophagus (Dv and Vd) were assessed for correlation with grade 2 acute toxicity. RESULTS: Incidence of grade 2 acute toxicity was 12% (n=15). Highly significant logistic models were generated for D(5)cc and Dmax (p<0.001). To keep the complication rate <20%, the model requires that D(5)cc26.3 BED(1)(0). At 2 years, the probability of complication with BED(1)(0)D(5)cc>14.4 Gy was 24%, compared to 1.6% if 14.4 Gy. CONCLUSIONS: This novel analysis provides guidelines to predict acute esophageal toxicity in lung SBRT. Dose to the hottest 5cc and Dmax of the esophagus were the best predictors of toxicity. Converting the BED(1)(0) limits to physical doses, D(5)cc to the esophagus should be kept less than 16.8, 18.1 and 19.0 Gy for 3, 4, and 5 fractions, respectively, to keep the acute toxicity rate <20%. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Wu, Abraham J AU - Wu AJ AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA. Electronic address: wua@mskcc.org. FAU - Williams, Eric AU - Williams E AD - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, USA. FAU - Modh, Ankit AU - Modh A AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA. FAU - Foster, Amanda AU - Foster A AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA. FAU - Yorke, Ellen AU - Yorke E AD - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, USA. FAU - Rimner, Andreas AU - Rimner A AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA. FAU - Jackson, Andrew AU - Jackson A AD - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, USA. LA - eng GR - R01 CA129182/CA/NCI NIH HHS/United States GR - R01 CA129182/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140723 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 SB - IM MH - Adult MH - Aged MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery MH - Cohort Studies MH - Esophagitis/*etiology MH - Esophagus/*radiation effects MH - Female MH - Humans MH - Logistic Models MH - Lung Neoplasms/pathology/*surgery MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Predictive Value of Tests MH - Proportional Hazards Models MH - Radiation Injuries/*etiology MH - Radiosurgery/*adverse effects/methods MH - Risk Factors PMC - PMC4254177 MID - NIHMS616813 OID - NLM: NIHMS616813 [Available on 08/01/15] OID - NLM: PMC4254177 [Available on 08/01/15] OTO - NOTNLM OT - Central OT - Esophagitis OT - Esophagus OT - Hypofractionated OT - Lung OT - SBRT EDAT- 2014/07/30 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/07/28 06:00 PMCR- 2015/08/01 00:00 PHST- 2014/05/31 [received] PHST- 2014/06/30 [revised] PHST- 2014/07/06 [accepted] PHST- 2014/07/23 [aheadofprint] AID - S0167-8140(14)00287-4 [pii] AID - 10.1016/j.radonc.2014.07.001 [doi] PST - ppublish SO - Radiother Oncol. 2014 Aug;112(2):267-71. doi: 10.1016/j.radonc.2014.07.001. Epub 2014 Jul 23. PMID- 25057939 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer. PG - 1385-92 LID - 10.1097/JTO.0000000000000238 [doi] AB - INTRODUCTION: Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on treatment outcome of advanced non-small-cell lung cancer (NSCLC). METHODS: We prospectively collected tissue samples, blood, and clinical data from two cohorts of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall survival (OS) and progression-free survival (PFS) to epidermal growth factor receptor (EGFR) TKIs and chemotherapy treatment. RESULTS: BIM deletion polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.004). Among 120 patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for patients with wild-type BIM and BIM deletion polymorphism, respectively (p = 0.005). Multivariate analyses suggested that BIM deletion polymorphism was an independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p = 0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039). CONCLUSIONS: BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS in advanced NSCLC. FAU - Lee, Jih-Hsiang AU - Lee JH AD - *Department of Oncology; daggerNational Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital; double daggerGraduate Institute of Oncology and Cancer Research Center; section signGraduate Institute of Clinical Medicine; ||College of Medicine; paragraph signCollege of Life Science, National Taiwan University; #Institute of Statistical Science, Academia Sinica; **Department of Medical Imaging; and daggerdaggerDepartment of Internal Medicine, National Taiwan University Hospital, Taiwan. FAU - Lin, Yu-Lin AU - Lin YL FAU - Hsu, Wei-Hsun AU - Hsu WH FAU - Chen, Hsuan-Yu AU - Chen HY FAU - Chang, Yeun-Chung AU - Chang YC FAU - Yu, Chong-Jen AU - Yu CJ FAU - Shih, Jin-Yuan AU - Shih JY FAU - Lin, Chia-Chi AU - Lin CC FAU - Chen, Kuan-Yu AU - Chen KY FAU - Ho, Chao-Chi AU - Ho CC FAU - Laio, Wei-Yu AU - Laio WY FAU - Yang, Pan-Chyr AU - Yang PC FAU - Yang, James Chih-Hsin AU - Yang JC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Bcl-2-like protein 11) RN - 0 (DNA, Neoplasm) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) SB - IM MH - Apoptosis Regulatory Proteins/*genetics/metabolism MH - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/mortality MH - DNA Mutational Analysis MH - DNA, Neoplasm/*genetics MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*genetics/metabolism/mortality MH - Male MH - Membrane Proteins/*genetics/metabolism MH - Middle Aged MH - *Mutation MH - Polymerase Chain Reaction MH - *Polymorphism, Genetic MH - Prognosis MH - Prospective Studies MH - Proto-Oncogene Proteins/*genetics/metabolism MH - Sequence Deletion MH - Survival Rate/trends MH - Taiwan/epidemiology EDAT- 2014/07/25 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/07/25 06:00 AID - 10.1097/JTO.0000000000000238 [doi] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1385-92. doi: 10.1097/JTO.0000000000000238. PMID- 25048725 OWN - NLM STAT- MEDLINE DA - 20140722 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Elevated expression of CRYAB predicts unfavorable prognosis in non-small cell lung cancer. PG - 142 LID - 10.1007/s12032-014-0142-1 [doi] AB - Alpha B-crystallin (CRYAB) is one of the principal members of the small heat-shock protein family, and several studies described the CRYAB expression in human cancers. However, the association between CRYAB expression and the clinical features of non-small cell lung cancer (NSCLC) is rarely elucidated. In this present study, one-step quantitative reverse transcription-polymerase chain reaction with 12 fresh-frozen NSCLC samples and Western blotting as well as immunohistochemistry (IHC) analyses in 101 NSCLC cases were conducted to investigate the relationship between CRYAB expression and the clinicopathological attributes of NSCLC. The results showed that CRYAB mRNA and protein expression levels were significantly higher in NSCLC than in matched non-cancerous tissues (p < 0.05). The IHC data indicated that the CRYAB protein expression in NSCLC was significantly correlated with TNM stage (p = 0.043), and overall survival (p = 0.029). Kaplan-Meier method and Cox multifactor analysis suggested that higher CRYAB protein level (p = 0.032) and TNM stage (p = 0.048) were statistically associated with the poor survival of patients with NSCLC. The data suggested that CRYAB may be identified as a novel prognostic marker and targeting CRYAB may provide a promising strategy for NSCLC treatment. FAU - Qin, Hui AU - Qin H AD - Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China, asplbeibei@163.com. FAU - Ni, Yijiang AU - Ni Y FAU - Tong, Jichun AU - Tong J FAU - Zhao, Jiabi AU - Zhao J FAU - Zhou, Xiaoli AU - Zhou X FAU - Cai, Wei AU - Cai W FAU - Liang, Jie AU - Liang J FAU - Yao, Xin AU - Yao X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140722 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (CRYAB protein, human) RN - 0 (Tumor Markers, Biological) RN - 0 (alpha-Crystallin B Chain) SB - IM MH - Aged MH - Blotting, Western MH - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/mortality/*pathology MH - Case-Control Studies MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry/methods MH - Lung Neoplasms/genetics/*metabolism/mortality/*pathology MH - Lymphatic Metastasis/genetics/pathology MH - Male MH - Middle Aged MH - Prognosis MH - Retrospective Studies MH - Survival Analysis MH - Tumor Markers, Biological/genetics/metabolism MH - alpha-Crystallin B Chain/genetics/*metabolism EDAT- 2014/07/23 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/07/23 06:00 PHST- 2014/06/29 [received] PHST- 2014/07/15 [accepted] PHST- 2014/07/22 [aheadofprint] AID - 10.1007/s12032-014-0142-1 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):142. doi: 10.1007/s12032-014-0142-1. Epub 2014 Jul 22. PMID- 25043903 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: a meta-analysis. PG - 339-45 LID - 10.1016/j.lungcan.2014.06.011 [doi] LID - S0169-5002(14)00269-4 [pii] AB - BACKGROUND: This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. METHOD: We systematically identified eligible articles investigating the effects of chemotherapy in patients with NSCLC stratified by EGFR mutation status. The summary risk ratio (RR) for ORR and hazard ratios (HRs) for both PFS and OS were calculated using the inverse variance formula of meta-analysis. RESULTS: Identification for the current meta-analysis: 5 prospective studies (n=875) and 18 retrospective studies (n=1934) for ORR; 2 prospective studies (n=434) and 10 retrospective studies (n=947) for PFS; 2 prospective studies (n=438) and 7 retrospective studies (n=711) for OS. The ORR was significantly higher in patients with EGFR mutations in prospective studies (RR=1.42; 95% confidence interval [CI], 1.16-1.74; P=0.001), but not in retrospective studies (RR=1.12; 95% CI, 0.96-1.32; P=0.146). There was no obvious association between EGFR mutations and PFS both in prospective (HR=0.84; 95% CI: 0.65-1.09; P=0.197) and retrospective (HR=1.02; 95% CI: 0.87-1.18; P=0.838) studies. Association between EGFR mutations and OS was also not seen in prospective studies (HR=0.74; 95% CI: 0.27-2.05; P=0.566), but was seen in retrospective studies (HR=0.48; 95% CI: 0.33-0.72; P<0.001; I(2)=75.9%; P<0.001) with significant heterogeneity. CONCLUSION: EGFR mutations in advanced NSCLC may be associated with higher ORRs to chemotherapy, but may have nothing to do with PFS and OS. Further prospective studies are required to identify the influence of EGFR mutations on chemotherapy effects in advanced NSCLC. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Zhang, Qiong AU - Zhang Q AD - Tumor Research and Therapy Center, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, PR China. FAU - Dai, Hong-Hai AU - Dai HH AD - Tumor Research and Therapy Center, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, PR China. FAU - Dong, Hong-Yun AU - Dong HY AD - School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong 250012, PR China; Wanhua Chemical Group Co., Ltd., 7 South Xingfu Road, Yantai, Shandong 264002, PR China. FAU - Sun, Cheng-Tao AU - Sun CT AD - Tumor Research and Therapy Center, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, PR China. FAU - Yang, Zhe AU - Yang Z AD - Tumor Research and Therapy Center, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, PR China. Electronic address: sdslyyyz@sina.com. FAU - Han, Jun-Qing AU - Han JQ AD - Tumor Research and Therapy Center, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, PR China. Electronic address: hanjq1960@126.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140708 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/mortality/pathology MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics/mortality/pathology MH - *Mutation MH - Neoplasm Staging MH - Odds Ratio MH - Publication Bias MH - Receptor, Epidermal Growth Factor/*genetics MH - Treatment Outcome OTO - NOTNLM OT - Chemotherapy OT - EGFR OT - Meta-analysis OT - Mutation status OT - Non-small cell lung cancer OT - Response rate EDAT- 2014/07/22 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/07/22 06:00 PHST- 2013/10/11 [received] PHST- 2014/04/20 [revised] PHST- 2014/06/13 [accepted] PHST- 2014/07/08 [aheadofprint] AID - S0169-5002(14)00269-4 [pii] AID - 10.1016/j.lungcan.2014.06.011 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):339-45. doi: 10.1016/j.lungcan.2014.06.011. Epub 2014 Jul 8. PMID- 25043642 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - Multicenter phase II study evaluating docetaxel and cisplatin as neoadjuvant induction regimen prior to surgery or radiochemotherapy with docetaxel, followed by adjuvant docetaxel therapy in chemonaive patients with NSCLC stage II, IIIA and IIIB (TAX-AT 1.203 Trial). PG - 395-400 LID - 10.1016/j.lungcan.2014.06.019 [doi] LID - S0169-5002(14)00277-3 [pii] AB - OBJECTIVES: Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear. PATIENTS AND METHODS: In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction. RESULTS: After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively). CONCLUSION: Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Kocher, F AU - Kocher F AD - Department of Hematology and Oncology, Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria. Electronic address: florian.kocher@i-med.ac.at. FAU - Pircher, A AU - Pircher A AD - Department of Hematology and Oncology, Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria. FAU - Mohn-Staudner, A AU - Mohn-Staudner A AD - Department of Pulmonary Medicine II, SMZ Otto Wagner Hospital, Vienna, Austria. FAU - Romeder, F AU - Romeder F AD - Department of Internal Medicine III, Paracelsus Medical University Hospital, Salzburg, Austria. FAU - Duller, W AU - Duller W AD - Department of Pneumology, General Hospital of Linz, Linz, Austria. FAU - Steinmaurer, M AU - Steinmaurer M AD - Department of Pneumology, General Hospital Wels, Wels, Austria. FAU - Eckmayr, J AU - Eckmayr J AD - Department of Pneumology, General Hospital Wels, Wels, Austria. FAU - Schmid, T AU - Schmid T AD - Department of Visceral and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria. FAU - Hilbe, W AU - Hilbe W AD - Department of Hematology and Oncology, Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria. FAU - Fiegl, M AU - Fiegl M AD - Department of Hematology and Oncology, Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria. FAU - Greil, R AU - Greil R AD - Department of Internal Medicine III, Paracelsus Medical University Hospital, Salzburg, Austria. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20140703 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Taxoids) RN - 15H5577CQD (docetaxel) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/*pathology/radiotherapy/surgery MH - Chemoradiotherapy MH - Chemotherapy, Adjuvant MH - Cisplatin/administration & dosage MH - Combined Modality Therapy MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/*pathology/radiotherapy/surgery MH - Male MH - Middle Aged MH - Neoadjuvant Therapy MH - Neoplasm Staging MH - Taxoids/administration & dosage MH - Treatment Outcome OTO - NOTNLM OT - Cisplatin OT - Docetaxel OT - Induction OT - Neoadjuvant OT - Non-small cell lung cancer (NSCLC) OT - Radiochemotherapy OT - Surgery EDAT- 2014/07/22 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/07/22 06:00 PHST- 2014/03/25 [received] PHST- 2014/06/25 [revised] PHST- 2014/06/26 [accepted] PHST- 2014/07/03 [aheadofprint] AID - S0169-5002(14)00277-3 [pii] AID - 10.1016/j.lungcan.2014.06.019 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):395-400. doi: 10.1016/j.lungcan.2014.06.019. Epub 2014 Jul 3. PMID- 25036876 OWN - NLM STAT- MEDLINE DA - 20140815 DCOM- 20150512 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 9 IP - 9 DP - 2014 Sep TI - Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in non-small-cell lung cancer. PG - 1294-304 LID - 10.1097/JTO.0000000000000243 [doi] AB - INTRODUCTION: Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC) is still unclear. METHODS: We investigated the protein expression of apoptosis regulators Bcl-2, Bcl-xl, Mcl-1, and pp32/PHAPI, and the expression of the lncRNA MALAT-1 in tumor samples from 383 NSCLC patients (median age: 65.6 years; 77.5% male; paraffin-embedded tissue microarrays). For statistical analysis correlation tests, Log rank tests and Cox proportional hazard models were applied. RESULTS: Tumor histology was significantly associated with the expression of Bcl-2, Bcl-xl and Mcl-1 (all p < 0.001). Among the tested apoptotic markers only Bcl-2 demonstrated prognostic impact (hazard ratio = 0.64, p = 0.012). For NSCLC patients with non-adenocarcinoma histology, Bcl-2 expression was associated with increased overall survival (p = 0.036). Besides tumor histology, prognostic impact of Bcl-2 was also found to depend on MALAT-1 lncRNA expression. Gene expression analysis of A549 adenocarcinoma cells with differential MALAT-1 lncRNA expression demonstrated an influence on the expression of Bcl-2 and its interacting proteins. CONCLUSIONS: Bcl-2 expression was specifically associated with superior prognosis in localized NSCLC. An interaction of Bcl-2 with MALAT-1 lncRNA expression was revealed, which merits further investigation for risk prediction in resectable NSCLC patients. FAU - Schmidt, Lars Henning AU - Schmidt LH AD - *Department of Medicine A, Hematology, Oncology and Pulmonology, University Hospital Muenster; daggerInstitute of Biostatistics and Clinical Research, Westfaelische Wilhelms-Universitaet Muenster; double daggerGerhard-Domagk Institute of Pathology, University Hospital Muenster, Muenster; section signDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen; ||German Cancer Consortium (DKTK), Heidelberg; paragraph signIntegrated Functional Genomics, Interdisciplinary Center for Clinical Research, University of Muenster, Muenster; #Chest Surgery, Klinikum St. Georg, Ostercappeln, Ostercappeln, Germany; and **Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany. FAU - Gorlich, Dennis AU - Gorlich D FAU - Spieker, Tilmann AU - Spieker T FAU - Rohde, Christian AU - Rohde C FAU - Schuler, Martin AU - Schuler M FAU - Mohr, Michael AU - Mohr M FAU - Humberg, Julia AU - Humberg J FAU - Sauer, Tim AU - Sauer T FAU - Thoenissen, Nils H AU - Thoenissen NH FAU - Huge, Andreas AU - Huge A FAU - Voss, Reinhard AU - Voss R FAU - Marra, Alessandro AU - Marra A FAU - Faldum, Andreas AU - Faldum A FAU - Muller-Tidow, Carsten AU - Muller-Tidow C FAU - Berdel, Wolfgang E AU - Berdel WE FAU - Wiewrodt, Rainer AU - Wiewrodt R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (MALAT1 long non-coding RNA, human) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Neoplasm) RN - 0 (Tumor Markers, Biological) SB - IM MH - Aged MH - Apoptosis MH - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathology MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization MH - Lung Neoplasms/*genetics/metabolism/pathology MH - Male MH - Polymerase Chain Reaction MH - Prognosis MH - Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism MH - RNA, Long Noncoding/biosynthesis/*genetics MH - RNA, Neoplasm/*genetics MH - Tumor Markers, Biological/biosynthesis/genetics EDAT- 2014/07/19 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/07/19 06:00 AID - 10.1097/JTO.0000000000000243 [doi] PST - ppublish SO - J Thorac Oncol. 2014 Sep;9(9):1294-304. doi: 10.1097/JTO.0000000000000243. PMID- 25034625 OWN - NLM STAT- MEDLINE DA - 20140908 DCOM- 20150515 IS - 1421-9794 (Electronic) IS - 0009-3157 (Linking) VI - 59 IP - 6 DP - 2013 TI - Phase II study of pemetrexed and erlotinib in pretreated nonsquamous, non-small-cell lung cancer patients without an EGFR mutation. PG - 414-9 LID - 10.1159/000363731 [doi] AB - BACKGROUND: Preclinical data indicated that the combination of erlotinib and pemetrexed is synergistic when erlotinib is administered after pemetrexed. PATIENTS AND METHODS: This was a phase II study of pemetrexed and erlotinib in patients with pretreated advanced non-squamous non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR). Chemotherapy consisted of pemetrexed (500 mg/m(2)) on day 1 and erlotinib (150 mg/body) on days 2-15 every 3 weeks. The protocol treatment was repeated until disease progression or intolerable toxicities occurred. RESULTS: Seventeen patients were enrolled between January 2010 and January 2013, and 15 patients were evaluable for both safety and efficacy. The study was terminated due to slow patient accrual. There was 1 complete response. There was a partial response in 3 patients, stable disease in 4 and progressive disease in 7. The response rate was 27% and disease control rate was 53%. The median progression-free survival and overall survival were 2.5 months and 6.7 months, respectively. CONCLUSIONS: Statistical interpretation could not been made due to the early termination of the study. Further studies are needed to clarify the efficacy of this regimen in NSCLC patients without EGFR mutation (UMIN-CTR No. 0000024531). CI - (c) 2014 S. Karger AG, Basel. FAU - Kim, Young Hak AU - Kim YH AD - Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Nishimura, Takashi AU - Nishimura T FAU - Ozasa, Hiroaki AU - Ozasa H FAU - Nagai, Hiroki AU - Nagai H FAU - Sakamori, Yuichi AU - Sakamori Y FAU - Iwata, Toshiyuki AU - Iwata T FAU - Sunadome, Hironobu AU - Sunadome H FAU - Nishimura, Tomoko AU - Nishimura T FAU - Mishima, Michiaki AU - Mishima M LA - eng PT - Clinical Trial, Phase II PT - Journal Article DEP - 20140716 PL - Switzerland TA - Chemotherapy JT - Chemotherapy JID - 0144731 RN - 0 (Antineoplastic Agents) RN - 0 (Glutamates) RN - 0 (Quinazolines) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) SB - IM MH - Aged MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Disease-Free Survival MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Glutamates/adverse effects/*therapeutic use MH - Guanine/adverse effects/*analogs & derivatives/therapeutic use MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Mutation MH - Neutropenia/etiology MH - Quinazolines/adverse effects/*therapeutic use MH - Receptor, Epidermal Growth Factor/genetics/metabolism MH - Thrombocytopenia/etiology MH - Treatment Outcome EDAT- 2014/07/19 06:00 MHDA- 2015/05/16 06:00 CRDT- 2014/07/19 06:00 PHST- 2014/03/24 [received] PHST- 2014/05/05 [accepted] PHST- 2014/07/16 [aheadofprint] AID - 000363731 [pii] AID - 10.1159/000363731 [doi] PST - ppublish SO - Chemotherapy. 2013;59(6):414-9. doi: 10.1159/000363731. Epub 2014 Jul 16. PMID- 25030720 OWN - NLM STAT- MEDLINE DA - 20140811 DCOM- 20150515 IS - 2185-4610 (Electronic) IS - 0016-2590 (Linking) VI - 60 IP - 1 DP - 2014 TI - Prediction of recurrence for non-small cell lung cancer by combined analysis of molecular markers and 18F 2-fluoro-2-deoxy-D-glucose positron emission tomography. PG - 47-56 AB - PURPOSE: Numerous biomarkers have been reported to reflect prognosis in patients with non-small cell lung cancer, but most of them remain controversial in terms of the clinical benefits. The aim of this study is to establish a novel procedure in combined analyses of molecular markers and biomedical image for precise prediction for patient prognosis of non-small cell lung cancer. EXPERIMENTAL DESIGN: Molecular markers related to cell cycle and proliferation and (18)F 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) were retrospectively analyzed for their utility as prognostic parameters in 54 patients with non-small cell lung cancer. Expression of ten representative molecular markers (Glut-1, proliferating cell nuclear antigen, Ki-67, cyclin B1, cyclin D1, cyclin E, E2F-1, p21, p27, and p53) were immunohistochemically analyzed using tissue microarray. The maximum standardized uptake value (SUVmax) on FDG-PET was analyzed as a semiquantitative value of FDG uptake of the primary tumor. RESULTS: Several molecular markers were significantly correlated with some of clinicopathological parameters, whereas none of each marker were correlated with recurrence or survival. Hierarchical clustering analysis in combination of immunohistochemical analysis of molecular expressions and SUVmax divided them into three subgroups significantly different in two-year recurrent-free survival (Cluster A, 56.3%; B, 100%; C 93.8%). These clustering subgroups were also significantly correlated with disease recurrence (p=0.0282). CONCLUSIONS: Hierarchical clustering analysis, based on molecular markers and FDG accumulation, could be an efficient tool for prediction of recurrence and survival in patients with non-small cell lung cancer. FAU - Yonechi, Atsushi AU - Yonechi A AD - Department of Regenerative Surgery, Fukushima Medical University School of Medicine. FAU - Suzuki, Hiroyuki AU - Suzuki H FAU - Sakuma, Hideo AU - Sakuma H FAU - Higuchi, Mitsunori AU - Higuchi M FAU - Ohsugi, Jun AU - Ohsugi J FAU - Okabe, Naoyuki AU - Okabe N FAU - Muto, Satoshi AU - Muto S FAU - Teranishi, Yasushi AU - Teranishi Y FAU - Gotoh, Mitsukazu AU - Gotoh M LA - eng PT - Journal Article DEP - 20140715 PL - Japan TA - Fukushima J Med Sci JT - Fukushima journal of medical science JID - 0374626 RN - 0 (Biological Markers) RN - 0 (Radiopharmaceuticals) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) SB - IM MH - Aged MH - Aged, 80 and over MH - Biological Markers/metabolism MH - Carcinoma, Non-Small-Cell Lung/*metabolism/*radionuclide imaging MH - Female MH - Fluorodeoxyglucose F18/diagnostic use MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*metabolism/*radionuclide imaging MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*metabolism/*radionuclide imaging MH - Positron-Emission Tomography MH - Predictive Value of Tests MH - Radiopharmaceuticals/diagnostic use MH - Retrospective Studies MH - Tissue Array Analysis EDAT- 2014/07/18 06:00 MHDA- 2015/05/16 06:00 CRDT- 2014/07/18 06:00 PHST- 2014/07/15 [aheadofprint] AID - DN/JST.JSTAGE/fms/2010-20 [pii] PST - ppublish SO - Fukushima J Med Sci. 2014;60(1):47-56. Epub 2014 Jul 15. PMID- 25023055 OWN - NLM STAT- MEDLINE DA - 20140715 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Hepatitis B virus reactivation in hepatitis B surface antigen seropositive patients with metastatic non-small cell lung cancer receiving cytotoxic chemotherapy: the efficacy of preemptive lamivudine and identification of risk factors. PG - 119 LID - 10.1007/s12032-014-0119-0 [doi] AB - Little is known about the likelihood and degree of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) seropositive patients with disseminated non-small cell lung cancer (NSCLC) receiving chemotherapy. Between January 2003 and December 2013, all HBsAg seropositive patients with metastatic NSCLC receiving cytotoxic chemotherapy were retrospectively evaluated. The morbidity and mortality of HBV reactivation, risk factors associated with reactivation, as well as the efficacy of preemptive lamivudine were investigated. Of 258 patients who were eligible for the present study, 176 were treated without antiviral prophylaxis and 82 received preemptive lamivudine. Patients without lamivudine prophylaxis had a significantly higher prevalence of HBV reactivation (19.3 vs 6.1 %, p = 0.006) and severe hepatitis attributable to reactivation (11.8 vs 3.7 %, p = 0.034) than those with preemptive lamivudine. However, no significant difference in mortality due to reactivation was noted between patients with or without prophylactic lamivudine (0 vs 2.3 %, p = 0.310). Furthermore, patients who developed HBV reactivation were indentified to have a higher rate of HBeAg seropositivity (74.4 vs 43.4 %, p < 0.001), serum HBV-DNA level of 10(4) copies/ml or greater (76.9 vs 47.9 %, p = 0.001), coexisting liver metastasis (50.0 vs 40.6 %, p = 0.033) and treatment with more than 4 cycles of chemotherapy (56.4 vs 39.3 %, p = 0.046) than those who did not experienced reactivation. The current study has demonstrated that preemptive lamivudine significantly reduced the prevalence of HBV reactivation in HBsAg seropositive patients with metastatic NSCLC receiving systemic chemotherapy. FAU - Lin, Gui-Nan AU - Lin GN AD - Department of Medical Oncology, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, People's Republic of China. FAU - Peng, Jie-Wen AU - Peng JW FAU - Xiao, Jian-jun AU - Xiao JJ FAU - Liu, Dong-Ying AU - Liu DY FAU - Xia, Zhong-Jun AU - Xia ZJ LA - eng PT - Controlled Clinical Trial PT - Journal Article DEP - 20140715 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (Antineoplastic Agents) RN - 0 (Hepatitis B Surface Antigens) RN - 2T8Q726O95 (Lamivudine) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology/virology MH - Female MH - Hepatitis B/*prevention & control/virology MH - Hepatitis B Surface Antigens/blood MH - Hepatitis B virus/genetics/*pathogenicity MH - Humans MH - Lamivudine/*therapeutic use MH - Liver Neoplasms/*drug therapy/pathology/virology MH - Male MH - Middle Aged MH - Retrospective Studies MH - Risk Factors MH - Treatment Outcome MH - Virus Activation/*drug effects EDAT- 2014/07/16 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/07/16 06:00 PHST- 2014/06/23 [received] PHST- 2014/07/02 [accepted] PHST- 2014/07/15 [aheadofprint] AID - 10.1007/s12032-014-0119-0 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):119. doi: 10.1007/s12032-014-0119-0. Epub 2014 Jul 15. PMID- 25017413 OWN - NLM STAT- MEDLINE DA - 20140823 DCOM- 20150511 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 85 IP - 3 DP - 2014 Sep TI - EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib. PG - 435-41 LID - 10.1016/j.lungcan.2014.06.016 [doi] LID - S0169-5002(14)00274-8 [pii] AB - OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib. MATERIALS AND METHODS: Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based on the somatic EGFR mutation status. RESULTS: In EGFR mutation positive patients (N=62) we demonstrate a significantly higher median progression free survival (HR=0.39 (0.22-0.70); p=0.002) and overall survival (HR=0.43 (0.23-0.78); p=0.006) in patients also harboring a short CA repeat length vs. a long (median follow-up time of 52.2 months). The result remained highly significant in a multivariate Cox proportional hazards model. This correlation was not seen in EGFR mutation negative patients. CONCLUSION: Our study demonstrate that in EGFR mutation positive NSCLC patients treated with erlotinib a low number of CA repeats in intron 1 of the EGFR gene is a predictor for both longer progression free survival and overall survival. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Winther Larsen, Anne AU - Winther Larsen A AD - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: anlarsen@rm.dk. FAU - Nissen, Peter Henrik AU - Nissen PH AD - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. FAU - Meldgaard, Peter AU - Meldgaard P AD - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. FAU - Weber, Britta AU - Weber B AD - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. FAU - Sorensen, Boe Sandahl AU - Sorensen BS AD - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. LA - eng PT - Journal Article DEP - 20140628 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/mortality/pathology MH - Disease Progression MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics/mortality/pathology MH - Male MH - Middle Aged MH - *Mutation MH - *Polymorphism, Genetic MH - Protein Kinase Inhibitors/therapeutic use MH - Quinazolines/*therapeutic use MH - Receptor, Epidermal Growth Factor/*genetics MH - *Repetitive Sequences, Nucleic Acid MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - CA repeat OT - EGFR somatic mutations OT - Epidermal growth factor receptor OT - Erlotinib OT - Non-small cell lung cancer OT - Polymorphism EDAT- 2014/07/16 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/07/15 06:00 PHST- 2014/04/27 [received] PHST- 2014/06/20 [revised] PHST- 2014/06/21 [accepted] PHST- 2014/06/28 [aheadofprint] AID - S0169-5002(14)00274-8 [pii] AID - 10.1016/j.lungcan.2014.06.016 [doi] PST - ppublish SO - Lung Cancer. 2014 Sep;85(3):435-41. doi: 10.1016/j.lungcan.2014.06.016. Epub 2014 Jun 28. PMID- 25011542 OWN - NLM STAT- MEDLINE DA - 20140908 DCOM- 20150515 IS - 1421-9794 (Electronic) IS - 0009-3157 (Linking) VI - 59 IP - 6 DP - 2013 TI - Retrospective analysis of severe neutropenia in patients receiving concomitant administration of docetaxel and clarithromycin. PG - 407-13 LID - 10.1159/000362437 [doi] AB - BACKGROUND: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. METHODS: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. RESULTS: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. CONCLUSIONS: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression. CI - (c) 2014 S. Karger AG, Basel. FAU - Tsuji, Daiki AU - Tsuji D AD - Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. FAU - Kamezato, Mana AU - Kamezato M FAU - Daimon, Takashi AU - Daimon T FAU - Taku, Keisei AU - Taku K FAU - Hatori, Masahiro AU - Hatori M FAU - Ikeda, Midori AU - Ikeda M FAU - Hayashi, Hideki AU - Hayashi H FAU - Inoue, Kazuyuki AU - Inoue K FAU - Eto, Takashi AU - Eto T FAU - Itoh, Kunihiko AU - Itoh K LA - eng PT - Journal Article DEP - 20140708 PL - Switzerland TA - Chemotherapy JT - Chemotherapy JID - 0144731 RN - 0 (Antineoplastic Agents) RN - 0 (Taxoids) RN - 15H5577CQD (docetaxel) RN - H1250JIK0A (Clarithromycin) SB - IM MH - Aged MH - Antineoplastic Agents/*adverse effects/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy MH - Clarithromycin/administration & dosage/*adverse effects MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Humans MH - Lung Neoplasms/drug therapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Neutropenia/*etiology MH - Odds Ratio MH - Retrospective Studies MH - Severity of Illness Index MH - Sex Factors MH - Taxoids/administration & dosage/*adverse effects EDAT- 2014/07/12 06:00 MHDA- 2015/05/16 06:00 CRDT- 2014/07/12 06:00 PHST- 2013/12/13 [received] PHST- 2014/03/24 [accepted] PHST- 2014/07/08 [aheadofprint] AID - 000362437 [pii] AID - 10.1159/000362437 [doi] PST - ppublish SO - Chemotherapy. 2013;59(6):407-13. doi: 10.1159/000362437. Epub 2014 Jul 8. PMID- 24996882 OWN - NLM STAT- MEDLINE DA - 20140909 DCOM- 20150522 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 5 DP - 2014 Sep TI - Role of postoperative radiotherapy after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small-cell lung cancer: a propensity score matching analysis. PG - 356-64 LID - 10.1016/j.cllc.2014.05.005 [doi] LID - S1525-7304(14)00112-0 [pii] AB - BACKGROUND: The objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy was performed. Forty-one patients additionally received PORT. Propensity scores for PORT receipt were individually calculated and used for matching to compare the outcome between patients who did (+) and did not (-) receive PORT. One hundred eleven patients in the PORT (-) group and 38 patients in PORT (+) group were matched. Clinical and pathologic characteristics were well-balanced. RESULTS: The median follow-up duration was 48 months. In the matched patients, PORT resulted in a significantly lower crude locoregional relapse (43.2% vs. 23.7%; P = .032). Also, PORT was associated with improved locoregional control (LRC) rate (5-year LRC 63.7% vs. 48.6%; P = .036), but not distant metastasis-free survival, disease-free survival (DFS), and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5-year DFS, 43.2% vs. 16.6%; P = .037) and squamous cell carcinoma histology (5-year DFS, 70.1% vs. 23.3%; P = .011). CONCLUSIONS: Even in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC. Some subgroups appear to benefit from PORT in terms of DFS and LRC. Individualized strategies based on risk factors might be considered. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Kim, Byoung Hyuck AU - Kim BH AD - Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Hak Jae AU - Kim HJ AD - Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: khjae@snu.ac.kr. FAU - Wu, Hong-Gyun AU - Wu HG AD - Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kang, Chang Hyun AU - Kang CH AD - Department of Thoracic Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Young Tae AU - Kim YT AD - Department of Thoracic Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Lee, Se-Hoon AU - Lee SH AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Dong-Wan AU - Kim DW AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140606 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/pathology/*therapy MH - Carcinoma, Squamous Cell/pathology/*therapy MH - Chemotherapy, Adjuvant/methods MH - Combined Modality Therapy MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/pathology/*therapy MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local MH - Neoplasm Staging MH - Propensity Score MH - Retrospective Studies MH - Survival Rate OTO - NOTNLM OT - Adjuvant chemotherapy OT - Non-small-cell lung cancer OT - Pathologic N2 OT - Postoperative radiotherapy OT - Propensity score EDAT- 2014/07/06 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/07/06 06:00 PHST- 2014/03/16 [received] PHST- 2014/04/28 [revised] PHST- 2014/05/19 [accepted] PHST- 2014/06/06 [aheadofprint] AID - S1525-7304(14)00112-0 [pii] AID - 10.1016/j.cllc.2014.05.005 [doi] PST - ppublish SO - Clin Lung Cancer. 2014 Sep;15(5):356-64. doi: 10.1016/j.cllc.2014.05.005. Epub 2014 Jun 6. PMID- 24993594 OWN - NLM STAT- MEDLINE DA - 20140909 DCOM- 20150522 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 5 DP - 2014 Sep TI - Assessment of folate receptor-alpha and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients. PG - 320-30.e1-3 LID - 10.1016/j.cllc.2014.05.002 [doi] LID - S1525-7304(14)00109-0 [pii] AB - INTRODUCTION: Folate receptor-alpha regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed. PATIENTS AND METHODS: Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score >/= 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076). CONCLUSION: Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Christoph, Daniel C AU - Christoph DC AD - Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. FAU - Reyna-Asuncion, Bernadette AU - Reyna-Asuncion B AD - Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. FAU - Hassan, Biftu AU - Hassan B AD - Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. FAU - Tran, Cindy AU - Tran C AD - Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. FAU - Maltzman, Julia D AU - Maltzman JD AD - Morphotek Inc, Exton, PA. FAU - O'Shannessy, Daniel J AU - O'Shannessy DJ AD - Morphotek Inc, Exton, PA. FAU - Gauler, Thomas C AU - Gauler TC AD - Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Wohlschlaeger, Jeremias AU - Wohlschlaeger J AD - Department of Pathology and Neuropathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Schuler, Martin AU - Schuler M AD - Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Eberhardt, Wilfried E AU - Eberhardt WE AD - Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Hirsch, Fred R AU - Hirsch FR AD - Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO. Electronic address: fred.hirsch@ucdenver.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140603 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 RN - 0 (Antineoplastic Agents) RN - 0 (Folate Receptor 1) RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Disease-Free Survival MH - Female MH - Folate Receptor 1/genetics MH - Gene Expression Regulation, Neoplastic MH - Glutamates/*therapeutic use MH - Guanine/*analogs & derivatives/therapeutic use MH - Humans MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Receptor, Epidermal Growth Factor/genetics MH - Retrospective Studies MH - Survival Rate MH - Young Adult OTO - NOTNLM OT - Antifolate chemotherapy OT - Combination of targeted agents OT - Correlation of receptor expression OT - Predictive biomarker OT - Therapeutic antibody EDAT- 2014/07/06 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/07/05 06:00 PHST- 2014/02/11 [received] PHST- 2014/04/08 [revised] PHST- 2014/05/19 [accepted] PHST- 2014/06/03 [aheadofprint] AID - S1525-7304(14)00109-0 [pii] AID - 10.1016/j.cllc.2014.05.002 [doi] PST - ppublish SO - Clin Lung Cancer. 2014 Sep;15(5):320-30.e1-3. doi: 10.1016/j.cllc.2014.05.002. Epub 2014 Jun 3. PMID- 24984565 OWN - NLM STAT- MEDLINE DA - 20140909 DCOM- 20150522 LR - 20150326 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 5 DP - 2014 Sep TI - The effect of radiotherapy dose on survival in stage III non-small-cell lung cancer patients undergoing definitive chemoradiotherapy. PG - 365-71 LID - 10.1016/j.cllc.2014.05.004 [doi] LID - S1525-7304(14)00111-9 [pii] AB - BACKGROUND: In this study, we examined trends in the radiotherapy dose prescribed and the effect of dose escalation on survival in patients with stage III lung cancer. MATERIALS AND METHODS: Radiation dose prescription patterns were analyzed for 38,848 patients in the National Cancer Database with clinical stage III disease who underwent concurrent chemoradiation between 2004 and 2011 to a dose between 57 and 80 Gy. Survival information was available for patients diagnosed from 2004 to 2006 (n = 12,024). Overall survival (OS) was estimated using Kaplan-Meier methods. Cox proportional hazard regression was used to estimate hazard ratios (HRs). RESULTS: The percentage of patients treated to >/= 64 Gy increased from 50% in 2004 to 62% in 2011 (P < .001). The 5-year OS was 12% for patients treated between 57 and 59.3 Gy, 14% for patients treated at 59.4 to 62.9 Gy, 16% for patients treated at 63 to 66 Gy and 66.1 to 73.9 Gy, and 13% for patients treated at 74 to 80 Gy (P < .0001). In multivariate analysis, the estimated HR (95% confidence interval) was 1.3 (1.1-1.6) for 57 to 59.3 Gy, 1.0 (0.9-1.2) for 59.4 to 62.9 Gy, 0.9 (0.9-1.2) for 63 to 66 Gy, 0.9 (0.8-1.1) for 66.1 to 73.9 Gy, and 1.0 (referent) for the 74 to 80 Gy cohort. There was no significant difference in the HR for the dose groups > 59.4 Gy compared with the 74 to 80 Gy cohort. CONCLUSION: There was no improvement in OS with radiotherapy dose escalation beyond 59.4 Gy for patients with unresectable clinical stage III lung cancer treated with chemoradiation. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Koshy, Matthew AU - Koshy M AD - Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL. Electronic address: mkoshy@radonc.uchicago.edu. FAU - Malik, Renu AU - Malik R AD - Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL. FAU - Sher, David J AU - Sher DJ AD - Department of Radiation Oncology, Rush University Medical Center, Chicago, IL. FAU - Spiotto, Michael AU - Spiotto M AD - Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL. FAU - Mahmood, Usama AU - Mahmood U AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. FAU - Aydogan, Bulent AU - Aydogan B AD - Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL. FAU - Weichselbaum, Ralph R AU - Weichselbaum RR AD - Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL. LA - eng PT - Journal Article DEP - 20140602 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/pathology/*therapy MH - Chemoradiotherapy/*methods MH - Female MH - Follow-Up Studies MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/pathology/*therapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Proportional Hazards Models MH - Radiotherapy Dosage MH - Retrospective Studies MH - Survival Rate MH - Young Adult OTO - NOTNLM OT - Chemoradiation OT - Dose Escalation OT - Locally Advanced Lung Cancer OT - Radiation Therapy EDAT- 2014/07/06 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/07/03 06:00 PHST- 2014/04/01 [received] PHST- 2014/05/07 [revised] PHST- 2014/05/19 [accepted] PHST- 2014/06/02 [aheadofprint] AID - S1525-7304(14)00111-9 [pii] AID - 10.1016/j.cllc.2014.05.004 [doi] PST - ppublish SO - Clin Lung Cancer. 2014 Sep;15(5):365-71. doi: 10.1016/j.cllc.2014.05.004. Epub 2014 Jun 2. PMID- 24973952 OWN - NLM STAT- MEDLINE DA - 20140630 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. PG - 87 LID - 10.1007/s12032-014-0087-4 [doi] AB - EGFR and KRAS mutation profile in non-small cell lung cancers (NSCLCs) shows wide variations due to geographic and ethnic background. We aimed to determine the frequency and types of EGFR and KRAS mutations in a sample group of Turkish NSCLC cases. The study included 14 adenocarcinomas (ACs), 11 squamous cell carcinoma (SCC) patients selected from archival material including small biopsy or surgical specimens. Their formalin fixed paraffin-embedded tumor tissues were used for genomic DNA extraction for EGFR exon 19 and 21, and KRAS exon 2 mutations. Eleven NSCLCs (44 %) had EGFR mutations. Exon 19 and 21 mutations were found in 8 (32 %) and 5 (20 %) cases. Two cases showed double EGFR mutations. In ACs, 5 (35.7 %) patients had EGFR gene mutation, 3 in exon 19 and 3 in exon 21. In SCCs, 6 (54.5 %) cases had EGFR mutation, 5 in exon 19 and 2 in exon 21. All exon 19 mutations were deletion-type mutations. For exon 21, 3 cases had L858R point mutation (CTG>CGG) and two cases showed deletion-type mutations. Six (24 %) NSCLCs showed KRAS mutations (three ACC, three SCC), 5 codon 12 mutations (G>T, T>C, G>A) and one codon 13 mutation (G>T). Three NSCLC cases showed both EGFR and KRAS mutations together. The profile of KRAS mutation in our AC cases was quite similar to those seen in the Western countries; however, frequency and clustering of EGFR mutations were similar to those seen in the Eastern countries. FAU - Bircan, Sema AU - Bircan S AD - Department of Pathology, School of Medicine, Suleyman Demirel University, Isparta, Turkey, bircans2000@yahoo.com. FAU - Baloglu, Huseyin AU - Baloglu H FAU - Kucukodaci, Zafer AU - Kucukodaci Z FAU - Bircan, Ahmet AU - Bircan A LA - eng PT - Journal Article DEP - 20140629 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (KRAS protein, human) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - EC 3.6.5.2 (ras Proteins) SB - IM MH - Adenocarcinoma/genetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Carcinoma, Squamous Cell/genetics MH - Exons MH - Female MH - Humans MH - Lung Neoplasms/*genetics MH - Male MH - Middle Aged MH - *Mutation MH - Mutation Rate MH - Pilot Projects MH - Proto-Oncogene Proteins/*genetics MH - Receptor, Epidermal Growth Factor/*genetics MH - Smoking/genetics MH - Turkey MH - ras Proteins/*genetics EDAT- 2014/06/30 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/30 06:00 PHST- 2014/05/06 [received] PHST- 2014/06/16 [accepted] PHST- 2014/06/29 [aheadofprint] AID - 10.1007/s12032-014-0087-4 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):87. doi: 10.1007/s12032-014-0087-4. Epub 2014 Jun 29. PMID- 24961467 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Individual-level data on the relationships of progression-free survival and post-progression survival with overall survival in patients with advanced non-squamous non-small cell lung cancer patients who received second-line chemotherapy. PG - 88 LID - 10.1007/s12032-014-0088-3 [doi] AB - The effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). Given the lack of research in this area, we here examined whether progression-free survival (PFS) or post-progression survival (PPS) could serve as valid surrogate endpoints for OS after second-line chemotherapy in advanced NSCLC, using individual-level data. Between April 2009 and June 2011, 39 patients with advanced non-squamous NSCLC who had received second-line chemotherapy following first-line chemotherapy treatment with cisplatin and pemetrexed were analysed. The relationships of PFS and PPS with OS were analysed at the individual level. Spearman rank correlation analyses and linear regression analyses showed that PPS was strongly associated with OS (r = 0.90, p < 0.05, R (2) = 0.85), whereas PFS only moderately correlated with OS (r = 0.76, p < 0.05, R (2) = 0.50). Best response at third-line treatment and number of regimens employed after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Analysis of individual-level data of patients treated with second-line chemotherapy suggested that PPS may be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Moreover, our findings suggest that subsequent treatment after disease progression following second-line chemotherapy may greatly influence OS. However, these results should be validated in further large-scale studies. FAU - Imai, Hisao AU - Imai H AD - Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-chou, Suntou-gun, Shizuoka, 411-8777, Japan, hi.imai@scchr.jp. FAU - Mori, Keita AU - Mori K FAU - Ono, Akira AU - Ono A FAU - Akamatsu, Hiroaki AU - Akamatsu H FAU - Taira, Tetsuhiko AU - Taira T FAU - Kenmotsu, Hirotsugu AU - Kenmotsu H FAU - Naito, Tateaki AU - Naito T FAU - Kaira, Kyoichi AU - Kaira K FAU - Murakami, Haruyasu AU - Murakami H FAU - Endo, Masahiro AU - Endo M FAU - Nakajima, Takashi AU - Nakajima T FAU - Takahashi, Toshiaki AU - Takahashi T LA - eng PT - Clinical Trial PT - Journal Article DEP - 20140625 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*mortality/pathology MH - Cisplatin/administration & dosage MH - Disease-Free Survival MH - Female MH - Glutamates/administration & dosage MH - Guanine/administration & dosage/analogs & derivatives MH - Humans MH - Lung Neoplasms/*drug therapy/*mortality/pathology MH - Male MH - Middle Aged MH - Neoplasms, Squamous Cell/drug therapy/pathology MH - Treatment Outcome EDAT- 2014/06/26 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/26 06:00 PHST- 2014/02/26 [received] PHST- 2014/06/16 [accepted] PHST- 2014/06/25 [aheadofprint] AID - 10.1007/s12032-014-0088-3 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):88. doi: 10.1007/s12032-014-0088-3. Epub 2014 Jun 25. PMID- 24961465 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Nuclear survivin expression: a prognostic factor for the response to taxane-platinum chemotherapy in patients with advanced non-small cell lung cancer. PG - 79 LID - 10.1007/s12032-014-0079-4 [doi] AB - Survivin, a structurally unique protein expressed in most common human neoplasms, is thought to support cell cycle progression and suppress apoptosis. Survivin expression is highly correlated with advanced non-small cell lung cancer (NSCLC) and poor prognosis. In this retrospective study of banked pathology tissue of patients with advanced NSCLC, we tested for correlations of N-survivin expression in tumor tissues and responsiveness to treatment with platinum-based regimens containing paclitaxel or docetaxel. The 48 patients with NSCLC included 32 (66.7 %) males and 16 (33.3 %) females. Mean age at diagnosis was 59.4 years (range 36-83 years), and median follow-up time was 20.4 months (range 3.4-59.0 months). Patients with high tumor N-survivin expression had significantly better responses to taxane-platinum chemotherapy than those with low tumor N-survivin expression (P < 0.001). Adjusted multivariate modeling found high tumor N-survivin expression to be an independent prognostic factor for a clinical response to chemotherapy (high vs. low, OR 6.14, 95 % CI 1.62-23.29; P = 0.008). Median overall survival differed significantly between those with high tumor N-survivin expression who did/did not respond to chemotherapy and between those with low tumor N-survivin expression who did/did not respond to chemotherapy (P < 0.05). Tumor N-survivin expression shows promise as a predictive biomarker in the chemotherapy setting as a surrogate marker of high proliferation status. FAU - Wu, Yao-Kuang AU - Wu YK AD - Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan. FAU - Huang, Chun-Yao AU - Huang CY FAU - Yang, Mei-Chen AU - Yang MC FAU - Lan, Chou-Chin AU - Lan CC FAU - Lee, Chih-Hsin AU - Lee CH FAU - Chan, Err-Cheng AU - Chan EC FAU - Chen, Kuei-Tien AU - Chen KT LA - eng PT - Clinical Trial PT - Journal Article DEP - 20140625 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (BIRC5 protein, human) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Taxoids) RN - 0 (Tumor Markers, Biological) RN - 15H5577CQD (docetaxel) RN - 33069-62-4 (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology MH - Cell Nucleus/metabolism MH - Cell Proliferation/drug effects MH - Cisplatin/administration & dosage MH - Female MH - Humans MH - Inhibitor of Apoptosis Proteins/analysis/*metabolism MH - Lung Neoplasms/*drug therapy/mortality/pathology MH - Male MH - Middle Aged MH - Paclitaxel/administration & dosage MH - Predictive Value of Tests MH - Prognosis MH - Taxoids/administration & dosage MH - Treatment Outcome MH - Tumor Markers, Biological/analysis/*metabolism EDAT- 2014/06/26 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/26 06:00 PHST- 2014/04/17 [received] PHST- 2014/06/13 [accepted] PHST- 2014/06/25 [aheadofprint] AID - 10.1007/s12032-014-0079-4 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):79. doi: 10.1007/s12032-014-0079-4. Epub 2014 Jun 25. PMID- 24958519 OWN - NLM STAT- MEDLINE DA - 20140624 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Genetic polymorphism of GSTP1 and ERCC1 correlated with response to platinum-based chemotherapy in non-small cell lung cancer. PG - 86 LID - 10.1007/s12032-014-0086-5 [doi] AB - The study aims to investigate whether the glutathione S transferase P1 (GSTP1) and excision repair cross-complementing group 1 (ERCC1) polymorphism influence the response to treatment with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Ninety-one patients with metastatic non-small lung cancer were evaluated. Blood samples were obtained from each patient before chemotherapy. They are all administered modified TP, GP, NP regimens. Curative effects in patients were evaluated after at least two cycles of treatment. TTP was calculated. The response rate of GSTP1 with G/G + G/A group and A/A group is 54.55 % (24/44) and 21.28 % (10/47) (P = 0.001), respectively. The response rate of ERCC1 with C/C group and C/T + T/T group is 51.11 % (23/45) and 23.91 % (11/46) (P = 0.007), respectively. Patients with both G/G + G/A and C/C has the response rate of 64.52 % (20/31) (P = 0.000). Logistic regression analysis shows a significant increased chance of treatment response in patients with G/G + G/A genotype versus A/A genotype (P = 0.008) and with T/T + C/T genotype versus C/C genotype (P = 0.001). The median TTP of all patients is 7.32 months. The TTP of individuals with G/G + G/A genotype is 9.56 months, and those with A/A genotype had an TTP of 5.23 months. The TTP of individuals with C/C genotype is 9.16 months, and those with T/T + C/T genotype is 5.53 months. Kaplan-Meier analysis shows that ERCC1 and GSTP1 polymorphisms are correlated with TTP. The log-rank test is was marginally significant (P < 0.01). GSTP1 and ERCC1 polymorphism are correlated with response to platinum-based chemotherapy and have prognostic value for TTP. FAU - Lv, Hongying AU - Lv H AD - Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, 266003, People's Republic of China, doclvhongying@163.com. FAU - Han, Ting AU - Han T FAU - Shi, Xiaoli AU - Shi X FAU - Yao, Yasai AU - Yao Y FAU - Yao, Yongru AU - Yao Y FAU - Qiu, Wensheng AU - Qiu W FAU - Yue, Lu AU - Yue L FAU - Liang, Jun AU - Liang J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140624 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (DNA-Binding Proteins) RN - EC 2.5.1.18 (GSTP1 protein, human) RN - EC 2.5.1.18 (Glutathione S-Transferase pi) RN - EC 3.1.- (ERCC1 protein, human) RN - EC 3.1.- (Endonucleases) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Asian Continental Ancestry Group/genetics MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality MH - Cisplatin/administration & dosage MH - DNA-Binding Proteins/*genetics MH - Endonucleases/*genetics MH - Female MH - Gene Frequency MH - Glutathione S-Transferase pi/*genetics MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/genetics/mortality MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Treatment Outcome EDAT- 2014/06/25 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/25 06:00 PHST- 2014/05/09 [received] PHST- 2014/06/15 [accepted] PHST- 2014/06/24 [aheadofprint] AID - 10.1007/s12032-014-0086-5 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):86. doi: 10.1007/s12032-014-0086-5. Epub 2014 Jun 24. PMID- 24958518 OWN - NLM STAT- MEDLINE DA - 20140624 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Which tyrosine kinase inhibitor should be recommended as initial treatment for non-small cell lung cancer patients with EGFR mutations? PG - 78 LID - 10.1007/s12032-014-0078-5 [doi] AB - Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations derive greater benefits from first- and second-generation tyrosine kinase inhibitors (TKIs) than from chemotherapy, especially in the first-line setting. Thus, main treatment guidelines indicate to test all patients with lung adenocarcinoma for these genetic abnormalities and recommend the employment of TKIs in these patients. However, many unanswered questions about the optimal use of TKIs in lung cancer remain; in particular, an open question is which of the currently available TKIs (gefitinib, erlotinib and afatinib) might be the best choice in untreated NSCLC patients. In the current review, we will analyze the state of EGFR-TKIs therapy in untreated EGFR-mutated NSCLC patients with a focus on both efficacy and toxicity. FAU - Tartarone, Alfredo AU - Tartarone A AD - Unit of Medical Oncology, Department of Onco-Hematology, IRCCS, Centro di Riferimento Oncologico della Basilicata, I.R.C.C.S., Via Padre Pio 1, 85028, Rionero in Vulture, PZ, Italy, tarta1@virgilio.it. FAU - Lerose, Rosa AU - Lerose R FAU - Lazzari, Chiara AU - Lazzari C FAU - Gregorc, Vanesa AU - Gregorc V FAU - Aieta, Michele AU - Aieta M LA - eng PT - Journal Article PT - Review DEP - 20140624 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) RN - S65743JHBS (gefitinib) SB - IM MH - Antineoplastic Agents/adverse effects/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics MH - Humans MH - Lung Neoplasms/*drug therapy/genetics MH - Mutation MH - Protein Kinase Inhibitors/adverse effects/*pharmacology/*therapeutic use MH - Quinazolines/pharmacology/therapeutic use MH - Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics EDAT- 2014/06/25 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/25 06:00 PHST- 2014/04/09 [received] PHST- 2014/06/12 [accepted] PHST- 2014/06/24 [aheadofprint] AID - 10.1007/s12032-014-0078-5 [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):78. doi: 10.1007/s12032-014-0078-5. Epub 2014 Jun 24. PMID- 24958515 OWN - NLM STAT- MEDLINE DA - 20140624 DCOM- 20150514 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 31 IP - 8 DP - 2014 Aug TI - Pemetrexed plus dendritic cells as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer who had treatment with TKI. PG - 63 LID - 10.1007/s12032-014-0063-z [doi] AB - The aim of this study was to determine the efficacy and toxicity of pemetrexed plus dendritic cells (DCs) in patients suffering from stage IIIB or IV lung adenocarcinoma, who had undergone maintenance treatment with gefitinib or erlotinib. Patients who had failed gefitinib or erlotinib maintenance treatment had ECOG performance statuses ranging from 0 to 2.27 patients received pemetrexed plus DCs as second-line treatment. Dosage: 500 mg/m(2) pemetrexed was administered on day 1 of a 21-day cycle. DCs were given for one cycle of 21 days. Three patients (11.1 %) experienced a partial response and 14 patients (51.9 %) showed stable disease. Ten patients (37.0 %) had progressive disease. The median time to progression-free survival (PFS) was 4.8 months [95 % confidence interval (CI) 4.4-5.2], and the median overall survival was 10.7 months (95 % CI 10.3-11.2). In the subgroup analysis, PFS had a significant difference between the low ratio of CD4/CD8 and normal ratio of CD4/CD8, with 4.5 months (95 % CI 4.2-4.9) and 5.0 months (95 % CI 4.5-5.7), (Log Rank = 0.039), respectively. No one patient experienced grade 4 toxicity. A regimen of pemetrexed combined with DCs is marginally effective and well tolerated in patients with stage IIIB or IV lung adenocarcinoma who had received gefitinib or erlotinib first-line treatment. FAU - Hu, Rong-Hang AU - Hu RH AD - Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining, People's Republic of China. FAU - Shi, Sheng-Bin AU - Shi SB FAU - Qi, Jie-Lin AU - Qi JL FAU - Tian, Jing AU - Tian J FAU - Tang, Xiao-Yong AU - Tang XY FAU - Liu, Guo-Fang AU - Liu GF FAU - Chang, Chun-Xiao AU - Chang CX LA - eng PT - Clinical Trial PT - Journal Article DEP - 20140624 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - 0 (Enzyme Inhibitors) RN - 0 (Glutamates) RN - 04Q9AIZ7NO (pemetrexed) RN - 5Z93L87A1R (Guanine) RN - Adenocarcinoma of lung SB - IM MH - Adenocarcinoma/drug therapy/mortality/pathology/therapy MH - Adult MH - Aged MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology/therapy MH - Dendritic Cells/*transplantation MH - Disease-Free Survival MH - Enzyme Inhibitors/adverse effects/*therapeutic use MH - Female MH - Glutamates/adverse effects/*therapeutic use MH - Guanine/adverse effects/*analogs & derivatives/therapeutic use MH - Humans MH - Immunotherapy/adverse effects/methods MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/mortality/pathology/therapy MH - Male MH - Middle Aged MH - Treatment Outcome EDAT- 2014/06/25 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/25 06:00 PHST- 2014/05/03 [received] PHST- 2014/05/30 [accepted] PHST- 2014/06/24 [aheadofprint] AID - 10.1007/s12032-014-0063-z [doi] PST - ppublish SO - Med Oncol. 2014 Aug;31(8):63. doi: 10.1007/s12032-014-0063-z. Epub 2014 Jun 24. PMID- 24925923 OWN - NLM STAT- MEDLINE DA - 20140801 DCOM- 20150514 IS - 1399-3003 (Electronic) IS - 0903-1936 (Linking) VI - 44 IP - 2 DP - 2014 Aug TI - Surgical and nonsurgical approaches to small-size nonsmall cell lung cancer. PG - 483-94 LID - 10.1183/09031936.00020214 [doi] AB - Lobectomy and systematic nodal dissection are still the standard for small-size (<3 cm) nonsmall cell lung cancer. There is growing interest in more parenchyma-sparing surgery, so-called sublobar resections (wedge resection or segmentectomy). Indeed, nonrandomised trials suggest that a segmentectomy may result in local control rates that are similar to lobectomy. Nonsurgical approaches, such as stereotactic ablative radiotherapy, consistently result in local control rates of approximately 90% and survival rates that are comparable to lobectomy. Therefore, we are moving towards an era in which several therapeutic possibilities are available, that are probably equivalent from an oncological point of view. Further trials are needed to define the optimal therapy for individual patients. CI - (c)ERS 2014. FAU - De Ruysscher, Dirk AU - De Ruysscher D AD - Dept of Radiation Oncology, University Hospitals Leuven/KU Leuven, Leuven, Belgium Both authors contributed equally dirk.deruysscher@uzleuven.be. FAU - Nakagawa, Kazuo AU - Nakagawa K AD - Thoracic Surgery Division, National Cancer Center Hospital, Tokyo, Japan Both authors contributed equally. FAU - Asamura, Hisao AU - Asamura H AD - Thoracic Surgery Division, National Cancer Center Hospital, Tokyo, Japan. LA - eng PT - Journal Article PT - Review DEP - 20140612 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 SB - IM MH - Carcinoma, Non-Small-Cell Lung/pathology/*surgery/*therapy MH - Catheter Ablation MH - Clinical Trials as Topic MH - Humans MH - Lung/surgery MH - Lung Neoplasms/pathology/*surgery/*therapy MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Pneumonectomy MH - Radiosurgery MH - Thoracic Surgery, Video-Assisted MH - Treatment Outcome EDAT- 2014/06/14 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/14 06:00 PHST- 2014/06/12 [aheadofprint] AID - 09031936.00020214 [pii] AID - 10.1183/09031936.00020214 [doi] PST - ppublish SO - Eur Respir J. 2014 Aug;44(2):483-94. doi: 10.1183/09031936.00020214. Epub 2014 Jun 12. PMID- 24925809 OWN - NLM STAT- MEDLINE DA - 20140909 DCOM- 20150522 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 5 DP - 2014 Sep TI - Management of Italian patients with advanced non-small-cell lung cancer after second-line treatment: results of the longitudinal phase of the LIFE observational study. PG - 338-45.e1 LID - 10.1016/j.cllc.2014.04.004 [doi] LID - S1525-7304(14)00078-3 [pii] AB - INTRODUCTION/BACKGROUND: Patients with advanced NSCLC who experience disease progression after second-line therapy might receive further active treatment. LIFE was an Italian cohort multicenter observational study composed of a cross-sectional and a longitudinal phase. PATIENTS AND METHODS: In the longitudinal phase, described here, the primary aim was to determine the proportion of patients receiving third-line therapy among those who received second-line active treatment according to clinical practice. The proportion of patients receiving further treatment lines was also estimated. RESULTS: The longitudinal phase was conducted between January and August 2012. Of 464 patients who began second-line therapy outside of clinical trials within the baseline evaluation, 56 (12.1%) were still receiving second-line therapy at the end of the observation period and 17 (3.7%) withdrew during or after second-line therapy. Of the remaining 391 patients, 158 (40.4%) received third-line treatment outside of clinical trials: 93 received a third-line chemotherapy and 65 a targeted agent. The main reason for interrupting third-line treatment was disease progression or death. During the same observation period, 25 of 113 patients who completed a third-line therapy received a fourth line of treatment. From diagnosis of NSCLC to the end of observation, biomarkers were tested in 323 patients (59.7%): epidermal growth factor receptor mutations in 315 (58.2%), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations in 83 (15.3%) and Anaplastic lymphoma kinase (ALK) translocation in 84 (15.5%). CONCLUSION: In Italian clinical practice, the proportion of patients with advanced NSCLC receiving more than 2 treatment lines of therapy is not negligible. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - de Marinis, Filippo AU - de Marinis F AD - UOC Pneumologia Oncologica, A.O. San Camillo Forlanini, Rome, Italy; Thoracic Oncology Division, European Institute of Oncology (IEO), Milan, Italy. Electronic address: filippo.demarinis@ieo.it. FAU - Ardizzoni, Andrea AU - Ardizzoni A AD - U.O. Oncologia Medica, Azienda Ospedaliera di Parma, Parma, Italy. FAU - Fontanini, Gabriella AU - Fontanini G AD - U.O. Oncologia II Univ., Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. FAU - Grossi, Francesco AU - Grossi F AD - S.S. Tumori Polmonari, IRCCS A.O.U. San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. FAU - Cappuzzo, Federico AU - Cappuzzo F AD - Oncologia, Ospedale di Livorno - Oncologia, Livorno, Italy. FAU - Novello, Silvia AU - Novello S AD - Oncologia, Universita di Torino; A.O.U. San Luigi Gonzaga, Orbassano, Italy. FAU - Santo, Antonio AU - Santo A AD - GIVOP (Gruppo Interdisciplinare Veronese Oncologia Polmonare), Ospedale Civile Maggiore Borgo Trento - Oncologia Medica D.O., Verona, Italy. FAU - Lorusso, Vito AU - Lorusso V AD - Oncologia Medica Pad. oncologico Ospedale V. Fazzi, Lecce, Italy. FAU - Cortinovis, Diego AU - Cortinovis D AD - UO Oncologia Medica Ospedale San Gerardo, Monza, Italy. FAU - Iurlaro, Monica AU - Iurlaro M AD - Boehringer Ingelheim S.p.A., Milano, Italy. FAU - Galetta, Domenico AU - Galetta D AD - Oncologia Medica IRCCS Giovanni Paolo II Ospedale Oncologico, Bari, Italy. FAU - Gridelli, Cesare AU - Gridelli C AD - Oncologia Medica, A.O.R.N. San Giuseppe Moscati, Avellino, Italy. CN - LIFE Study Team LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20140514 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 RN - 0 (Antineoplastic Agents) RN - 0 (KRAS protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Quinazolines) RN - 0 (Tumor Markers, Biological) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - EC 2.7.10.1 (anaplastic lymphoma kinase) RN - EC 3.6.5.2 (ras Proteins) RN - J4T82NDH7E (erlotinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Cohort Studies MH - Disease Progression MH - Female MH - Humans MH - Italy MH - Longitudinal Studies MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Proto-Oncogene Proteins/genetics MH - Quinazolines/therapeutic use MH - Receptor Protein-Tyrosine Kinases/genetics MH - Receptor, Epidermal Growth Factor/genetics MH - Tumor Markers, Biological/metabolism MH - ras Proteins/genetics OTO - NOTNLM OT - Chemotherapy OT - EGFR OT - Erlotinib OT - NSCLC OT - Third-line IR - Pedrazzoli P FIR - Pedrazzoli, Paolo IR - Siena S FIR - Siena, Salvatore IR - Alabiso O FIR - Alabiso, Oscar IR - Bilancia D FIR - Bilancia, Domenico IR - Cinieri S FIR - Cinieri, Saverio IR - Carteni G FIR - Carteni, Giacomo IR - Fasola G FIR - Fasola, Gianpiero IR - Ferrau F FIR - Ferrau, Francesco IR - Milella M FIR - Milella, Michele IR - Contu A FIR - Contu, Antonio IR - Giuffrida D FIR - Giuffrida, Dario IR - Illiano A FIR - Illiano, Alfonso IR - Ravaioli A FIR - Ravaioli, Alberto IR - Zaniboni A FIR - Zaniboni, Alberto IR - Bettini A FIR - Bettini, Anna IR - Caprioli A FIR - Caprioli, Alberto IR - Longo F FIR - Longo, Flavia IR - Cruciani G FIR - Cruciani, Giorgio IR - Defraia E FIR - Defraia, Efisio IR - Favaretto A FIR - Favaretto, Adolfo IR - Amadori D FIR - Amadori, Dino IR - Clerico M FIR - Clerico, Mario IR - Di Costanzo F FIR - Di Costanzo, Francesco IR - Gamucci T FIR - Gamucci, Teresa IR - Caruso M FIR - Caruso, Michele IR - Iacobelli S FIR - Iacobelli, Stefano IR - Pinotti G FIR - Pinotti, Graziella IR - Pozzessere D FIR - Pozzessere, Daniele IR - Maiello E FIR - Maiello, Evaristo IR - Marchetti P FIR - Marchetti, Paolo IR - Passalacqua R FIR - Passalacqua, Rodolfo IR - Pavesi L FIR - Pavesi, Lorenzo IR - Tortora G FIR - Tortora, Giampaolo IR - Aglietta M FIR - Aglietta, Massimo IR - Bianco R FIR - Bianco, Roberto IR - Brandes A FIR - Brandes, Alba IR - Ciuffreda L FIR - Ciuffreda, Libero IR - Daniele B FIR - Daniele, Bruno IR - Demichelis C FIR - Demichelis, Claudio IR - Romito S FIR - Romito, Sante IR - Tamberi S FIR - Tamberi, Stefano IR - Barni S FIR - Barni, Sandro IR - Barbieri F FIR - Barbieri, Fausto IR - Giordano M FIR - Giordano, Monica IR - Bracarda S FIR - Bracarda, Sergio IR - Crino L FIR - Crino, Lucio IR - Marzano N FIR - Marzano, Nicola IR - Merlano M FIR - Merlano, Marco IR - Numico G FIR - Numico, Gianmauro EDAT- 2014/06/14 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/06/14 06:00 PHST- 2014/01/17 [received] PHST- 2014/04/07 [revised] PHST- 2014/04/08 [accepted] PHST- 2014/05/14 [aheadofprint] AID - S1525-7304(14)00078-3 [pii] AID - 10.1016/j.cllc.2014.04.004 [doi] PST - ppublish SO - Clin Lung Cancer. 2014 Sep;15(5):338-45.e1. doi: 10.1016/j.cllc.2014.04.004. Epub 2014 May 14. PMID- 24923873 OWN - NLM STAT- MEDLINE DA - 20150115 DCOM- 20150512 LR - 20150115 IS - 1468-3296 (Electronic) IS - 0040-6376 (Linking) VI - 70 IP - 2 DP - 2015 Feb TI - The role of receipt and timeliness of treatment in socioeconomic inequalities in lung cancer survival: population-based, data-linkage study. PG - 138-45 LID - 10.1136/thoraxjnl-2014-205517 [doi] AB - BACKGROUND: Lung cancer survival is socioeconomically patterned, and socioeconomic inequalities in receipt of treatment have been demonstrated. In England, there are target waiting times for the referral (14 days) and treatment intervals (31 days from diagnosis, 62 days from GP referral). Socioeconomic inequalities in the time intervals from GP referral have been found. Cancer registry, Hospital Episode Statistics and lung cancer audit data were linked in order to investigate the contribution of these inequalities to socioeconomic inequalities in lung cancer survival. METHODS: Logistic regression was used to examine the likelihood of being alive 2 years after diagnosis, by socioeconomic position, for 22,967 lung cancer patients diagnosed in 2006-2009, and in a subset with stage recorded (n=5233). RESULTS: Socioeconomic inequalities in survival were found in a multivariable analysis adjusted for age, sex, histology, year, timely GP referral, performance status and comorbidity, with those in the most deprived socioeconomic group significantly less likely to be alive after 2 years (OR=0.77, 95% CI 0.66 to 0.88, p<0.001). When receipt of treatment was included in the analysis, the association no longer remained significant (OR=0.87, 95% CI 0.75 to 1.00, p=0.06). Addition of timeliness of treatment did not alter the conclusion. Patients treated within guideline targets had lower likelihood of two-year survival. CONCLUSIONS: Socioeconomic inequalities in survival from lung cancer were statistically explained by socioeconomic inequalities in receipt of treatment, but not by timeliness of referral and treatment. Further research is required to determine the currently unexplained socioeconomic variance in treatment rates. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Forrest, Lynne F AU - Forrest LF AD - Fuse, UKCRC Centre for Translational Research in Public Health, Newcastle University, Newcastle upon Tyne, UK Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK. FAU - Adams, Jean AU - Adams J AD - Fuse, UKCRC Centre for Translational Research in Public Health, Newcastle University, Newcastle upon Tyne, UK Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK. FAU - Rubin, Greg AU - Rubin G AD - Fuse, UKCRC Centre for Translational Research in Public Health, Newcastle University, Newcastle upon Tyne, UK Wolfson Research Institute, Durham University, Queen's Campus, Stockton on Tees, UK. FAU - White, Martin AU - White M AD - Fuse, UKCRC Centre for Translational Research in Public Health, Newcastle University, Newcastle upon Tyne, UK Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK. LA - eng GR - MR/K02325X/1/Medical Research Council/United Kingdom GR - British Heart Foundation/United Kingdom GR - Cancer Research UK/United Kingdom GR - Department of Health/United Kingdom GR - Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140612 PL - England TA - Thorax JT - Thorax JID - 0417353 SB - IM CIN - Thorax. 2015 Feb;70(2):108-9. PMID: 25311470 MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/economics/*mortality/therapy MH - England/epidemiology MH - Female MH - General Practice/statistics & numerical data MH - *Healthcare Disparities MH - Humans MH - Lung Neoplasms/economics/*mortality/therapy MH - Male MH - Middle Aged MH - Practice Guidelines as Topic MH - Referral and Consultation/statistics & numerical data MH - Small Cell Lung Carcinoma/economics/*mortality/therapy MH - *Social Class MH - Socioeconomic Factors MH - Survival Rate MH - Time Factors MH - Time-to-Treatment OTO - NOTNLM OT - Clinical Epidemiology OT - Lung Cancer OT - Non-Small Cell Lung Cancer OT - Small Cell Lung Cancer EDAT- 2014/06/14 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/06/14 06:00 PHST- 2014/06/12 [aheadofprint] AID - thoraxjnl-2014-205517 [pii] AID - 10.1136/thoraxjnl-2014-205517 [doi] PST - ppublish SO - Thorax. 2015 Feb;70(2):138-45. doi: 10.1136/thoraxjnl-2014-205517. Epub 2014 Jun 12. PMID- 24913066 OWN - NLM STAT- MEDLINE DA - 20140909 DCOM- 20150522 LR - 20150326 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 5 DP - 2014 Sep TI - Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with recurrent malignant pleural effusion. PG - 379-86 LID - 10.1016/j.cllc.2014.04.002 [doi] LID - S1525-7304(14)00076-X [pii] AB - INTRODUCTION/BACKGROUND: Non-small-cell lung cancer patients with malignant pleural effusion have a poor overall median survival (4.3 months). VEGF is a key regulator of pleural effusion production. It is unknown if pharmacological inhibition of VEGF signaling modifies the disease course of non-small-cell lung cancer patients with recurrent malignant pleural effusion. We report the final results of a single-arm phase II clinical trial of the VEGF receptor inhibitor, vandetanib, combined with intrapleural catheter placement in patients with non-small-cell lung cancer and recurrent malignant pleural effusion, to determine whether vandetanib reduces time to pleurodesis. PATIENTS AND METHODS: Non-small-cell lung cancer patients with proven metastatic disease to the pleural space using pleural fluid cytology or pleural biopsy who required intrapleural catheter placement were eligible for enrollment. On the same day of the intrapleural catheter insertion, the patients were started on a daily oral dose of 300 mg vandetanib, for a maximum of 10 weeks. The primary end point was time to pleurodesis, with response rate as the secondary end point. Exploratory analyses included measurement of pleural fluid cytokines and angiogenic factors before and during therapy. RESULTS: Twenty eligible patients were included in the trial. Eleven patients completed 10 weeks of treatment. Median time to pleurodesis was 35 days (95% confidence interval, 15-not applicable). Median time to pleurodesis in the historical cohort was 63 days (95% confidence interval, 45-86) when adjusted for Eastern Cooperative Oncology Group performance status /=2 pN2 lymph nodes (P=0.021). The POCRT group had a significantly lower local relapse (P=0.009) and distant metastasis (P=0.05) rates as compared to that of the POCT group. One case died of pyemia and 9 cases suffered from grade 3 and 4 acute radiation esophagitis. The two groups had similar and tolerable hematologic toxicities. CONCLUSIONS: Compared with POCT, POCRT increased both local/regional and distant DFS rate of the patients with IIIA-pN2 NSCLC, but not the OS rate. Considering the relatively small sample size of the current study, caution should be taken when adopting the conclusions. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Shen, Wen-yi AU - Shen WY AD - Department of Radiation Oncology, People's Hospital of Lianshui County, Huai'an, PR China. FAU - Ji, Jian AU - Ji J AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Zuo, Yang-song AU - Zuo YS AD - Department of Radiation Oncology, People's Hospital of Lianshui County, Huai'an, PR China. FAU - Pu, Juan AU - Pu J AD - Department of Radiation Oncology, People's Hospital of Lianshui County, Huai'an, PR China. FAU - Xu, Yan-mei AU - Xu YM AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Zong, Cheng-dong AU - Zong CD AD - Department of Radiation Oncology, Oncology Hospital of Huai'an, PR China. FAU - Tao, Guang-zhou AU - Tao GZ AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Chen, Xiao-fei AU - Chen XF AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Ji, Fu-zhi AU - Ji FZ AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Zhou, Xi-lei AU - Zhou XL AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Han, Ji-hua AU - Han JH AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. FAU - Wang, Cheng-shi AU - Wang CS AD - Department of Radiation Oncology, People's Hospital of Lianshui County, Huai'an, PR China. FAU - Yi, Jiang-guo AU - Yi JG AD - Department of Radiation Oncology, Oncology Hospital of Huai'an, PR China. FAU - Su, Xi-long AU - Su XL AD - Department of Radiation Oncology, Huai'an No. 2 People's Hospital, PR China. FAU - Zhu, Wei-guo AU - Zhu WG AD - Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, PR China. Electronic address: zwgjsha@163.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20131031 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 RN - 33069-62-4 (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) SB - IM CIN - Radiother Oncol. 2014 Aug;112(2):314-5. PMID: 25037929 MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy/radiotherapy/surgery/*therapy MH - Chemoradiotherapy MH - Chemotherapy, Adjuvant MH - Cisplatin/administration & dosage MH - Disease-Free Survival MH - Female MH - Humans MH - Lung Neoplasms/drug therapy/radiotherapy/surgery/*therapy MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/pathology MH - Paclitaxel/administration & dosage MH - Pneumonectomy MH - Postoperative Care MH - Survival Rate MH - Treatment Outcome OTO - NOTNLM OT - IIIA-pN2 OT - Non-small cell lung cancer OT - Postoperative concurrent radiochemotherapy OT - Surgery OT - Survival EDAT- 2013/11/05 06:00 MHDA- 2015/05/23 06:00 CRDT- 2013/11/05 06:00 PHST- 2013/06/10 [received] PHST- 2013/10/12 [revised] PHST- 2013/10/13 [accepted] PHST- 2013/10/31 [aheadofprint] AID - S0167-8140(13)00512-4 [pii] AID - 10.1016/j.radonc.2013.10.008 [doi] PST - ppublish SO - Radiother Oncol. 2014 Jan;110(1):120-5. doi: 10.1016/j.radonc.2013.10.008. Epub 2013 Oct 31. PMID- 24157245 OWN - NLM STAT- MEDLINE DA - 20140217 DCOM- 20150521 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 15 IP - 2 DP - 2014 Mar TI - Stereotactic body radiation therapy in octogenarians with stage I lung cancer. PG - 131-5 LID - 10.1016/j.cllc.2013.08.007 [doi] LID - S1525-7304(13)00184-8 [pii] AB - BACKGROUND: The purpose of this study was to describe our clinical experience using stereotactic body radiation therapy (SBRT) to treat medically inoperable stage I non-small-cell lung cancer (NSCLC) in very elderly patients. PATIENTS AND METHODS: Twenty-four consecutive octogenarians with stage I NSCLC were treated with SBRT between 2007 and 2011 at a single center. Median prescription dose was 48 Gy (range, 48-56). Follow-up clinical examination and computed tomography (CT) were performed every 2 to 3 months. RESULTS: Median age was 85 years (range, 80-89). Twenty-three (96%) patients had peripheral tumors, and median tumor size was 22 mm (range, 11-49). Tissue diagnosis was obtained in 16 (67%) patients. Median follow-up for all patients was 27.6 months (range, 4.3-61.2). The 24-month disease-free survival was 77% (95% confidence interval [CI], 61%-97%). The 24-month overall survival (OS) was 74% (95% CI, 57%-94%). No local failure (LF) was observed during the period of observation. Nodal failure (NF) and distant failure (DF) occurred in 2 and 4 patients, respectively. The cumulative incidence of competing mortality at 24 months was estimated at 13% (95% CI, 3%-30%). No difference in outcomes with or without tissue diagnosis was observed. No grade >/= 3 early or late treatment-related toxicities were observed. CONCLUSION: Octogenarians tolerate SBRT well, which makes it an attractive treatment option. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Sandhu, Ajay P AU - Sandhu AP AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. Electronic address: apsandhu@ucsd.edu. FAU - Lau, Steven K M AU - Lau SK AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Rahn, Douglas AU - Rahn D AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Nath, Sameer K AU - Nath SK AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Kim, Daniel AU - Kim D AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Song, William Y AU - Song WY AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Gulaya, Sachin AU - Gulaya S AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. FAU - Fuster, Mark M AU - Fuster MM AD - Division of Pulmonary and Critical Care Medicine, VA San Diego Healthcare System and Department of Medicine, University of California San Diego, La Jolla, CA. FAU - Bazhenova, Lyudmila AU - Bazhenova L AD - Division of Hematology and Oncology, Department of Medicine, University of California San Diego, La Jolla, CA. FAU - Mundt, Arno J AU - Mundt AJ AD - Department of Radiation Medicine and Applied Sciences, Moores University of California San Diego Cancer Center, La Jolla, CA. LA - eng GR - PHSGM07198/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131021 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 SB - IM MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/pathology/*surgery MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/mortality/pathology/*surgery MH - Male MH - Neoplasm Staging MH - Prognosis MH - *Radiosurgery MH - Retrospective Studies MH - Survival Rate OTO - NOTNLM OT - Elderly OT - Non-small-cell lung cancer OT - Stereotactic body radiation therapy EDAT- 2013/10/26 06:00 MHDA- 2015/05/23 06:00 CRDT- 2013/10/26 06:00 PHST- 2013/06/07 [received] PHST- 2013/07/23 [revised] PHST- 2013/08/06 [accepted] PHST- 2013/10/21 [aheadofprint] AID - S1525-7304(13)00184-8 [pii] AID - 10.1016/j.cllc.2013.08.007 [doi] PST - ppublish SO - Clin Lung Cancer. 2014 Mar;15(2):131-5. doi: 10.1016/j.cllc.2013.08.007. Epub 2013 Oct 21. PMID- 24100149 OWN - NLM STAT- MEDLINE DA - 20140318 DCOM- 20150521 LR - 20150522 IS - 1879-0887 (Electronic) IS - 0167-8140 (Linking) VI - 110 IP - 1 DP - 2014 Jan TI - Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. PG - 3-8 LID - 10.1016/j.radonc.2013.08.011 [doi] LID - S0167-8140(13)00396-4 [pii] AB - BACKGROUND: We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection. RESULTS: Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p=0.01) and 0.76 (p=0.02) for PORT vs. controls, respectively). Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%. CONCLUSIONS: This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery. CI - Copyright (c) 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. FAU - Billiet, Charlotte AU - Billiet C AD - Radiation Oncology. Electronic address: charlotte.billiet@uzleuven.be. FAU - Decaluwe, Herbert AU - Decaluwe H AD - Thoracic Surgery and Leuven Lung Cancer Group, University Hospitals Leuven/KU Leuven, Belgium. FAU - Peeters, Stephanie AU - Peeters S AD - Radiation Oncology. FAU - Vansteenkiste, Johan AU - Vansteenkiste J AD - Respiratory Oncology (Pneumology) and Leuven Lung Cancer Group, University Hospitals Leuven/KU Leuven, Belgium. FAU - Dooms, Christophe AU - Dooms C AD - Respiratory Oncology (Pneumology) and Leuven Lung Cancer Group, University Hospitals Leuven/KU Leuven, Belgium. FAU - Haustermans, Karin AU - Haustermans K AD - Radiation Oncology. FAU - De Leyn, Paul AU - De Leyn P AD - Thoracic Surgery and Leuven Lung Cancer Group, University Hospitals Leuven/KU Leuven, Belgium. FAU - De Ruysscher, Dirk AU - De Ruysscher D AD - Radiation Oncology. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20131004 PL - Ireland TA - Radiother Oncol JT - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology JID - 8407192 SB - IM CIN - Radiother Oncol. 2014 Aug;112(2):314-5. PMID: 25037929 EIN - Radiother Oncol. 2014 Nov;113(2):300-1 MH - Carcinoma, Non-Small-Cell Lung/*radiotherapy/surgery MH - Humans MH - Lung Neoplasms/*radiotherapy/surgery MH - Neoplasm Recurrence, Local/radiotherapy MH - Postoperative Period MH - Radiotherapy, Adjuvant MH - Survival Rate OTO - NOTNLM OT - Local tumor control OT - Modeling OT - Non-small cell lung cancer OT - PORT OT - Post-operative radiotherapy OT - Stage III OT - Survival EDAT- 2013/10/09 06:00 MHDA- 2015/05/23 06:00 CRDT- 2013/10/09 06:00 PHST- 2013/02/24 [received] PHST- 2013/08/07 [revised] PHST- 2013/08/07 [accepted] PHST- 2013/10/04 [aheadofprint] AID - S0167-8140(13)00396-4 [pii] AID - 10.1016/j.radonc.2013.08.011 [doi] PST - ppublish SO - Radiother Oncol. 2014 Jan;110(1):3-8. doi: 10.1016/j.radonc.2013.08.011. Epub 2013 Oct 4. PMID- 23912954 OWN - NLM STAT- MEDLINE DA - 20140819 DCOM- 20150512 IS - 1437-7772 (Electronic) IS - 1341-9625 (Linking) VI - 19 IP - 4 DP - 2014 Aug TI - Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer. PG - 594-600 LID - 10.1007/s10147-013-0602-1 [doi] AB - BACKGROUND: There are many complex and rare mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) other than the two classical mutations of L858R and exon 19 deletional mutation. The purpose of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs). METHODS: We analyzed 1,431 NSCLC patients who were treated with either gefitinib or erlotinib. Exons 18 to 21 of EGFR were analyzed by PCR and subjected to direct sequencing methods. RESULTS: Of 306 patients who had EGFR mutation, 24 patients (7.3 %) had complex mutations. The frequency of rare mutations was 10.3 %. Four groups were categorized [group A (N = 269): classical mutation alone; group B (N = 16): complex mutation with classical mutation; group C (N = 16): rare mutation alone or complex mutation with rare mutation; group D (N = 5); classical mutation with T790M]; the response rate (RR) to TKI was significantly different between each group (RR = 74.8 % in group A vs. 68.8 % in group B vs. 25.0 % in group C vs. 80.0 % in group D, P < 0.001). Progression-free survival (PFS) was also poorer in rare mutations (median PFS: 11.9 vs. 8.1 vs. 1.4 vs. 8.0 months, respectively, P < 0.001). CONCLUSIONS: NSCLC patients harboring rare mutations did not show consistent and favorable responses to EGFR TKI compared with those harboring classical mutations. However, complex mutations with classical mutations showed similar treatment efficacy toward EGFR TKI to that with classical mutations alone. FAU - Keam, Bhumsuk AU - Keam B AD - Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. FAU - Kim, Dong-Wan AU - Kim DW FAU - Park, Jin Hyun AU - Park JH FAU - Lee, Jeong-Ok AU - Lee JO FAU - Kim, Tae Min AU - Kim TM FAU - Lee, Se-Hoon AU - Lee SH FAU - Chung, Doo Hyun AU - Chung DH FAU - Heo, Dae Seog AU - Heo DS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130806 PL - Japan TA - Int J Clin Oncol JT - International journal of clinical oncology JID - 9616295 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - EC 2.7.10.1 (Receptor, Epidermal Growth Factor) RN - J4T82NDH7E (erlotinib) RN - S65743JHBS (gefitinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/pathology MH - Disease-Free Survival MH - Female MH - Humans MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Staging MH - Protein Kinase Inhibitors/*administration & dosage MH - Quinazolines/administration & dosage MH - Receptor, Epidermal Growth Factor/*genetics EDAT- 2013/08/06 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/08/06 06:00 PHST- 2013/05/10 [received] PHST- 2013/07/17 [accepted] PHST- 2013/08/06 [aheadofprint] AID - 10.1007/s10147-013-0602-1 [doi] PST - ppublish SO - Int J Clin Oncol. 2014 Aug;19(4):594-600. doi: 10.1007/s10147-013-0602-1. Epub 2013 Aug 6. PMID- 23842112 OWN - NLM STAT- MEDLINE DA - 20140726 DCOM- 20150512 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 8 DP - 2013 TI - Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer. PG - 179 LID - 10.1186/1748-717X-8-179 [doi] AB - INTRODUCTION: Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. METHODS: Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45-60) followed by an SBRT boost with an average dose of 25 Gy (range 20-30) given over 5 fractions. RESULTS: With a median follow-up of 14 months (range, 1-14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. CONCLUSION: Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. FAU - Karam, Sana D AU - Karam SD FAU - Horne, Zachary D AU - Horne ZD FAU - Hong, Robert L AU - Hong RL FAU - McRae, Don AU - McRae D FAU - Duhamel, David AU - Duhamel D FAU - Nasr, Nadim M AU - Nasr NM LA - eng PT - Journal Article DEP - 20130710 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 SB - IM MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/*surgery MH - Chemoradiotherapy/methods MH - Disease-Free Survival MH - Female MH - Fiducial Markers MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/mortality/*surgery MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Radiometry MH - Radiosurgery/adverse effects/*methods MH - Radiotherapy Planning, Computer-Assisted/methods PMC - PMC3720211 OID - NLM: PMC3720211 EDAT- 2013/07/12 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/07/12 06:00 PHST- 2013/04/30 [received] PHST- 2013/06/28 [accepted] PHST- 2013/07/10 [aheadofprint] AID - 1748-717X-8-179 [pii] AID - 10.1186/1748-717X-8-179 [doi] PST - epublish SO - Radiat Oncol. 2013 Jul 10;8:179. doi: 10.1186/1748-717X-8-179. PMID- 23824557 OWN - NLM STAT- MEDLINE DA - 20140819 DCOM- 20150512 IS - 1437-7772 (Electronic) IS - 1341-9625 (Linking) VI - 19 IP - 4 DP - 2014 Aug TI - The role of SHP-1 promoter 2 hypermethylation detection of lymph node micrometastasis in resectable stage I non-small cell lung cancer as a prognostic marker of disease recurrence. PG - 586-92 LID - 10.1007/s10147-013-0590-1 [doi] AB - BACKGROUND: Despite adequate surgical management of stage I non-small cell lung cancer (NSCLC), many patients still relapse. Nodal micrometastases which cannot be detected by the standard hematoxylin and eosin (H&E) method are the postulated mechanism. We conducted a study of an epithelial-specific methylation marker, SHP-1 promoter 2 (SHP1P2) methylation, as a potential molecular marker to determine its association with a high risk of disease relapse. MATERIAL AND METHOD: Lymph nodes from stage II-IIIA NSCLC patients were examined to explore the potential role of SHP1P2 methylation in detecting metastatic carcinoma according to H&E staining. Further study was done in lymph nodes from stage I NSCLC patients who underwent curative resection and follow-up at The King Chulalongkorn Memorial Hospital, Bangkok, Thailand. No adjuvant treatment was given, according to the standard treatment in that stage. Patients who relapsed within 40 months after resection were defined as high risk. RESULTS: The nodal SHP1P2 methylation level from stage II-IIIA NSCLC patients was significantly higher in the metastasis group, median 674 [0-3536] ng, compared with the no metastasis group, median 230 [0-3832] ng (p = 0.004). One-hundred and ninety-eight lymph nodes from stage I NSCLC patients were analyzed, including hilar and mediastinal nodes. With a median follow-up period of 65 [46-109] months, high SHP1P2 methylation levels of more than 140 ng in hilar lymph nodes were associated with early relapse, with sensitivity and specificity of 85 and 54 %, respectively (hazard ratio 5.3; 95 % confidence interval 5.0-5.6; p < 0.0001). CONCLUSION: A high level of SHP1P2 methylation of hilar lymph nodes from stage I NSCLC patients is associated with early relapse of disease. FAU - Vinayanuwattikun, Chanida AU - Vinayanuwattikun C AD - Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand, Chanida.Vi@chula.ac.th. FAU - Chantranuwat, Poonchavist AU - Chantranuwat P FAU - Sriuranpong, Virote AU - Sriuranpong V FAU - Mutirangura, Apiwat AU - Mutirangura A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130704 PL - Japan TA - Int J Clin Oncol JT - International journal of clinical oncology JID - 9616295 RN - 0 (Tumor Markers, Biological) RN - EC 3.1.3.48 (PTPN6 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6) SB - IM EIN - Int J Clin Oncol. 2014 Aug;19(4):593. Chanida, Vinayanuwattikun [corrected to Vinayanuwattikun, Chanida]; Poonchavist, Chantranuwat [corrected to Chantranuwat, Poonchavist]; Virote, Sriuranpong [corrected to Sriuranpong, Virote]; Apiwat, Mutirangura [corrected to Mutirangura, Apiwat] MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics/pathology/surgery MH - DNA Methylation/genetics MH - Female MH - Humans MH - Lymphatic Metastasis/*genetics/pathology MH - Male MH - Middle Aged MH - Neoplasm Micrometastasis/*genetics/pathology MH - Neoplasm Recurrence, Local/genetics/pathology/surgery MH - Neoplasm Staging MH - Prognosis MH - Promoter Regions, Genetic MH - Protein Tyrosine Phosphatase, Non-Receptor Type 6/diagnostic use/*genetics MH - Thailand MH - Tumor Markers, Biological/*genetics EDAT- 2013/07/05 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/07/05 06:00 PHST- 2013/04/17 [received] PHST- 2013/06/17 [accepted] PHST- 2013/07/04 [aheadofprint] AID - 10.1007/s10147-013-0590-1 [doi] PST - ppublish SO - Int J Clin Oncol. 2014 Aug;19(4):586-92. doi: 10.1007/s10147-013-0590-1. Epub 2013 Jul 4. PMID- 23774619 OWN - NLM STAT- MEDLINE DA - 20140821 DCOM- 20150513 IS - 2186-1005 (Electronic) IS - 1341-1098 (Linking) VI - 20 IP - 4 DP - 2014 TI - Mediastinal lymph-nodes metastasis beyond the lobe-specific: an independent risk factor toward worse prognoses. PG - 284-91 AB - PURPOSE: Five-year survival rates were widely dispersed in pN2 non-small cell lung cancer (NSCLC). The present study aims to investigate the prognosis of patients with lymph node metastasis beyond lobe-specific mediastinal regions. METHODS: A total of 654 pathologically proved N2-NSCLC patients were enrolled. All patients underwent a major pulmonary resection and radical mediastinal lymphadenectomy. Two separate groups were assigned according to the definition of lobe-specific nodal metastasis: Group LS (lobe-specific) and Group NLS (non-lobe-specific). Survival rates were calculated using Kaplan-Meier and Cox regression models. RESULTS: There were 376 cases in Group LS and 278 cases in Group NLS. Univariate analyses showed that the risk factors of 5-year survival were operation type, MLN positivity ratio, nodal station, nodal zone, and LS/NLS metastasis. The 5-year survival among those in Group LS was significantly better than that of Group NLS (27.5% vs. 11.7%, p <0.0001). Multivariate analysis confirmed that the grouping method of LS/NLS and number of involved nodal zones were the most prominent risk factors for 5-year survival. CONCLUSION: Lymph node metastasis beyond lobe-specific lymph nodes is an independent risk factor of 5-year survival and is associated with worse prognoses for N2 NSCLC patients. FAU - Sun, Yifeng AU - Sun Y AD - Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Gao, Wen AU - Gao W FAU - Zheng, Hui AU - Zheng H FAU - Jiang, Gening AU - Jiang G FAU - Chen, Chang AU - Chen C FAU - Zhang, Lei AU - Zhang L LA - eng PT - Journal Article DEP - 20130618 PL - Japan TA - Ann Thorac Cardiovasc Surg JT - Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia JID - 9703158 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/*secondary/surgery MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/mortality/*pathology/surgery MH - Lymph Node Excision MH - Lymph Nodes/*pathology/surgery MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Neoplasm Staging MH - Odds Ratio MH - Pneumonectomy MH - Proportional Hazards Models MH - Risk Factors MH - Time Factors MH - Treatment Outcome EDAT- 2013/06/19 06:00 MHDA- 2015/05/15 06:00 CRDT- 2013/06/19 06:00 PHST- 2013/06/18 [aheadofprint] AID - DN/JST.JSTAGE/atcs/oa.13-00028 [pii] PST - ppublish SO - Ann Thorac Cardiovasc Surg. 2014;20(4):284-91. Epub 2013 Jun 18. PMID- 23767810 OWN - NLM STAT- MEDLINE DA - 20140726 DCOM- 20150512 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 8 DP - 2013 TI - An in-silico comparison of proton beam and IMRT for postoperative radiotherapy in completely resected stage IIIA non-small cell lung cancer. PG - 144 LID - 10.1186/1748-717X-8-144 [doi] AB - INTRODUCTION: Post-operative radiotherapy (PORT) for stage IIIA completely-resected non-small cell lung cancer (CR-NSCLC) has been shown to improve local control; however, it is unclear that this translates into a survival benefit. One explanation is that the detrimental effect of PORT on critical organs at risk (OARs) negates its benefit. This study reports an in-silico comparative analysis of passive scattering proton therapy (PSPT)- and intensity modulated proton therapy (IMPT) with intensity modulated photon beam radiotherapy (IMRT) PORT. METHODS: The computed tomography treatment planning scans of ten patients with pathologic stage IIIA CR-NSCLC treated with IMRT were used. IMRT, PSPT, and IMPT plans were generated and analyzed for dosimetric endpoints. The proton plans were constructed with two or three beams. All plans were optimized to deliver 50.4 Gy(RBE) in 1.8 Gy(RBE) fractions to the target volume. RESULTS: IMPT leads to statistically significant reductions in maximum spinal cord, mean lung dose, lung volumes treated to 5, 10, 20, and 30 Gy (V5, V10, V20, V30), mean heart dose, and heart volume treated to 40 Gy (V40), when compared with IMRT or PSPT. PSPT reduced lung V5 but increased lung V20, V30, and heart and esophagus V40. CONCLUSIONS: IMPT demonstrates a large decrease in dose to all OARs. PSPT, while reducing the low-dose lung bath, increases the volume of lung receiving high dose. Reductions are seen in dosimetric parameters predictive of radiation pneumonitis and cardiac morbidity and mortality. This reduction may correlate with a decrease in dose-limiting toxicity and improve the therapeutic ratio. FAU - Berman, Abigail T AU - Berman AT FAU - Teo, Boon-Keng Kevin AU - Teo BK FAU - Dolney, Derek AU - Dolney D FAU - Swisher-McClure, Samuel AU - Swisher-McClure S FAU - Shahnazi, Kambiz AU - Shahnazi K FAU - Both, Stefan AU - Both S FAU - Rengan, Ramesh AU - Rengan R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20130615 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 SB - IM MH - Carcinoma, Non-Small-Cell Lung/pathology/*radiotherapy MH - Humans MH - Lung Neoplasms/pathology/*radiotherapy MH - Neoplasm Staging MH - Proton Therapy/*methods MH - Radiometry MH - Radiotherapy Planning, Computer-Assisted/*methods MH - Radiotherapy, Adjuvant/methods MH - Radiotherapy, Intensity-Modulated/*methods MH - Retrospective Studies PMC - PMC3695889 OID - NLM: PMC3695889 EDAT- 2013/06/19 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/06/18 06:00 PHST- 2013/01/22 [received] PHST- 2013/06/01 [accepted] PHST- 2013/06/15 [aheadofprint] AID - 1748-717X-8-144 [pii] AID - 10.1186/1748-717X-8-144 [doi] PST - epublish SO - Radiat Oncol. 2013 Jun 15;8:144. doi: 10.1186/1748-717X-8-144. PMID- 23680396 OWN - NLM STAT- MEDLINE DA - 20140729 DCOM- 20150512 IS - 1748-717X (Electronic) IS - 1748-717X (Linking) VI - 8 DP - 2013 TI - Dose-volumetric parameters and prediction of severe acute esophagitis in patients with locally-advanced non small-cell lung cancer treated with neoadjuvant concurrent hyperfractionated-accelerated chemoradiotherapy. PG - 122 LID - 10.1186/1748-717X-8-122 [doi] AB - BACKGROUND: To identify dose-volume parameters predictive for severity of acute esophagitis (CTC > grade 2) in locally-advanced non small-cell lung cancer (LA-NSCLC) patients treated with neoadjuvant concurrent hyperfractionated-accelerated chemoradiotherapy (HA-CRT) a retrospective analysis was performed. 88 patients were treated with HA-CRT followed by radical surgery. Predictive power of absolute oesophageal length, absolute and relative oesophageal volume included in the 95%-isodose, patient- and tumor-related factors for severity of acute esophagitis was assessed. FINDINGS: A total of 82 patients (93%) developed radiation-induced acute esophagitis. Grade 1 was documented in 1 (1%), grade 2 in 55 (67%), grade 3 in 23 (28%) and grade 4 in 3 (4%) patients, respectively. Absolute oesophageal volume included in the 95%-isodose (42.8 Gy) achieved 13.5 cm3 (range: 3 - 29 cm3). Of the tested variables in univariate analysis, absolute oesophageal volume included in the 95%-Isodose was found to be the only significant variable (p = 0.03) predicting severe acute esophagitis (CTC > grade 2). For this volume a gradation scale of the likelihood of severity was built. CONCLUSION: Increase of absolute oesophageal volume included in the 95%-isodose correlates with severity of acute esophagitis in LA-NSCLC patients treated with neo-adjuvant concurrent HA-CRT. FAU - Manapov, Farkhad AU - Manapov F FAU - Sepe, Susanna AU - Sepe S FAU - Niyazi, Maximilian AU - Niyazi M FAU - Belka, Claus AU - Belka C FAU - Friedel, Godehard AU - Friedel G FAU - Budach, Wilfried AU - Budach W LA - eng PT - Journal Article DEP - 20130517 PL - England TA - Radiat Oncol JT - Radiation oncology (London, England) JID - 101265111 SB - IM MH - Carcinoma, Non-Small-Cell Lung/*radiotherapy MH - Chemoradiotherapy/*adverse effects MH - Clinical Trials, Phase II as Topic MH - Dose Fractionation MH - Esophagitis/*etiology MH - Female MH - Humans MH - Lung Neoplasms/*radiotherapy MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy MH - Radiation Injuries/*etiology MH - Retrospective Studies PMC - PMC3694011 OID - NLM: PMC3694011 EDAT- 2013/05/18 06:00 MHDA- 2015/05/13 06:00 CRDT- 2013/05/18 06:00 PHST- 2013/01/22 [received] PHST- 2013/05/14 [accepted] PHST- 2013/05/17 [aheadofprint] AID - 1748-717X-8-122 [pii] AID - 10.1186/1748-717X-8-122 [doi] PST - epublish SO - Radiat Oncol. 2013 May 17;8:122. doi: 10.1186/1748-717X-8-122. PMID- 23211223 OWN - NLM STAT- MEDLINE DA - 20140903 DCOM- 20150501 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 37 IP - 2 DP - 2014 Apr TI - Gefitinib combined with stereotactic radiosurgery in previously treated patients with advanced non-small cell lung cancer. PG - 148-53 LID - 10.1097/COC.0b013e31826e071b [doi] AB - BACKGROUND: Disease progression remains the major challenge in the management of advanced (stage IIIb or IV) non-small cell lung cancer (NSCLC) after the failure of first-line or second-line chemotherapy, or even of targeted therapies such as gefitinib. The current study evaluated the tolerability and efficacy of stereotactic body radiation therapy (SBRT) in combined with gefitinib as a second-line or third-line treatment in patients with advanced NSCLC. METHODS: Fourteen advanced NSCLC patients showing disease progression after platinum-based chemotherapy regimens were recruited. Eligible patients started taking gefitinib (250 mg/d) 7 days before SBRT and continued for 1 year until disease progression, unacceptable toxicity or withdrawal of consent. SBRT was delivered in median 3 fractions within 3 to 5 days. Treatment-associated toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v.3.0). Local control was assessed according to the Response Evaluation Criteria in Solid Tumors criteria and symptom assessments were measured by the Functional Assessment of Cancer Therapy-Lung instrument (V4.0). RESULTS: With an overall median follow-up of 15.5 months (range, 4 to 27 mo), most patients were well tolerated with common side effects from grade 1 to 2. No grade 4 or higher toxicity was encountered. The clinical disease-related symptom improvement rate was reached 57.1% with the median duration of symptom improvement of 8.0 months. The 1-year local control and overall survival (OS) rates were 83.9% and 69.6%, respectively. The median progression-free survival and OS were 7.0 and 19.0 months, respectively. CONCLUSIONS: The SBRT combined with gefitinib is a promising treatment strategy for advanced (stage IIIb or IV) NSCLC after the failure of previously chemotherapy. This method improves local control and disease-related symptoms with tolerated toxicity, and even increases the progression-free survival and OS. FAU - Wang, Zhen AU - Wang Z AD - Departments of *Radiation Oncology daggerDermatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Zhu, Xi-Xu AU - Zhu XX FAU - Wu, Xin-Hu AU - Wu XH FAU - Li, Bing AU - Li B FAU - Shen, Tian-Ze AU - Shen TZ FAU - Kong, Qing-Tao AU - Kong QT FAU - Li, Jing AU - Li J FAU - Liu, Zhi-Bing AU - Liu ZB FAU - Jiang, Wan-Rong AU - Jiang WR FAU - Wang, Yang AU - Wang Y FAU - Hou, Bo AU - Hou B LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 RN - 0 (Antineoplastic Agents) RN - 0 (Quinazolines) RN - S65743JHBS (gefitinib) SB - IM MH - Adenocarcinoma/drug therapy/mortality/pathology/surgery MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology/*surgery MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/mortality/pathology/*surgery MH - Male MH - Middle Aged MH - Quinazolines/adverse effects/*therapeutic use MH - *Radiosurgery/adverse effects MH - Treatment Outcome EDAT- 2012/12/06 06:00 MHDA- 2015/05/02 06:00 CRDT- 2012/12/06 06:00 AID - 10.1097/COC.0b013e31826e071b [doi] PST - ppublish SO - Am J Clin Oncol. 2014 Apr;37(2):148-53. doi: 10.1097/COC.0b013e31826e071b. PMID- 23111363 OWN - NLM STAT- MEDLINE DA - 20140903 DCOM- 20150501 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 37 IP - 2 DP - 2014 Apr TI - Phase II study of biweekly carboplatin, gemcitabine, and bevacizumab as first-line treatment in patients with stage IIIB/IV NSCLC. PG - 140-3 LID - 10.1097/COC.0b013e31826b9e12 [doi] AB - BACKGROUND: This study was initiated to assess the safety and efficacy of biweekly carboplatin and gemcitabine with bevacizumab in treatment-naive patients with advanced and metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: An open-label, nonrandomized phase II clinical trial was conducted. Treatment consisted of a biweekly cycle of gemcitabine, carboplatin, and bevacizumab for a maximum of 6 cycles. If no disease progression or intolerable side effects were observed, maintenance therapy with bevacizumab was continued until disease progressed. Progression-free survival, overall survival (OS), objective response rate, and the safety and tolerability of the therapy were assessed. RESULTS: Treatment was administered to 35 patients with stage IIIB/IV NSCLC. Median age of the patients was 64.5 years, with 58% being male. Median number of cycles of treatment was 6 (range, 4 to 28 cycles); median number of days of treatment was 117 days (range, 43 to 451 d). Sixty-six percent of patients experienced grade >/=3 toxicities. Hypertension (19%) was the most common adverse event. Pulmonary hemorrhage (3%) and pulmonary abscess (3%) were the causes of treatment-related deaths. There were 48% patients with partial response, 23% with stable disease, and 29% with progressive disease. Median progression-free survival was 2.6 months [95% confidence interval (CI), 1.6-3.4], and median OS was 13.4 months (95% CI, 8.4-24). The 2-year OS rate was 30% (95% CI, 12%-51%). CONCLUSIONS: Biweekly therapy with combination of carboplatin, gemcitabine, and bevacizumab in advanced inoperable NSCLC provided limited benefit and was associated with excessive toxicity. Further testing of this regimen is not recommended. CLINICALTRIALSGOV IDENTIFIER: NCT00400803. FAU - Dudek, Arkadiusz Z AU - Dudek AZ AD - *University of Minnesota Masonic Cancer Center, Minneapolis double daggerHubert H. Humphrey Cancer Center-North Memorial Health Care, Robbinsdale, MN daggerDepartment of Medicine, University of North Dakota, Fargo, ND. FAU - Kumar, Priya AU - Kumar P FAU - H Thaw, Sunn Sunn AU - H Thaw SS FAU - Cao, Qing AU - Cao Q FAU - Pawloski, Pamala AU - Pawloski P FAU - Larson, Timothy AU - Larson T LA - eng SI - ClinicalTrials.gov/NCT00400803 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0W860991D6 (Deoxycytidine) RN - 2S9ZZM9Q9V (bevacizumab) RN - B76N6SBZ8R (gemcitabine) RN - BG3F62OND5 (Carboplatin) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Disease-Free Survival MH - Drug Administration Schedule MH - Female MH - Humans MH - Hypertension/chemically induced MH - Lung Neoplasms/*drug therapy/mortality MH - Male MH - Middle Aged MH - Prospective Studies MH - Treatment Outcome EDAT- 2012/11/01 06:00 MHDA- 2015/05/02 06:00 CRDT- 2012/11/01 06:00 AID - 10.1097/COC.0b013e31826b9e12 [doi] PST - ppublish SO - Am J Clin Oncol. 2014 Apr;37(2):140-3. doi: 10.1097/COC.0b013e31826b9e12. PMID- 23111361 OWN - NLM STAT- MEDLINE DA - 20140903 DCOM- 20150501 IS - 1537-453X (Electronic) IS - 0277-3732 (Linking) VI - 37 IP - 2 DP - 2014 Apr TI - Prognostic value of primary tumor FDG uptake for occult mediastinal lymph node involvement in clinically N2/N3 node-negative non-small cell lung cancer. PG - 135-9 LID - 10.1097/COC.0b013e31826b9cd3 [doi] AB - OBJECTIVES: The objective of this study was to identify predictive factors of occult mediastinal nodal involvement on staging positron emission tomography with F-fluorodeoxyglucose in patients with non-small cell lung cancer. METHODS: We performed a retrospective review of 665 patients with suspected non-small cell lung cancer who underwent staging positron emission tomography with F-fluorodeoxyglucose from January 1, 2000 through August 31, 2010 at the Hospital of the University of Pennsylvania with clinical stage I or II disease and no evidence of N2 or N3 involvement on staging positron emission tomography (PET). A total of 201 of these patients underwent invasive pathologic staging of the mediastinum at the Hospital of the University of Pennsylvania with pathology reports available at the time of review. RESULTS: A total of 63 of the 201 patients were found to have N2 disease at the time of pathologic staging. The mean standardized uptake value (SUV) of the primary tumor for patients with occult N2 metastases was significantly higher than the node-negative patients (SUV 9.31 vs. 7.24, P=0.04). Histology, tumor location (central vs. peripheral), sex, and age were not predictive for occult N2 disease. A multivariate analysis was performed and identified primary tumor SUV>6 was the only significant predictor (P=0.02). An analysis by quartile identified a primary tumor SUV>10 to have an odds ratio of 1.72 compared with an SUV<4 of occult N2 involvement. CONCLUSIONS: Increased primary tumor SUV predicted for increased risk of mediastinal nodal disease. Tumor location was not predictive of PET-occult mediastinal nodal involvement, in contrast to previous publications. Pathologic staging of the mediastinum should be strongly considered in these patients even with a negative mediastinum on PET. FAU - Trister, Andrew D AU - Trister AD AD - *Department of Radiation Oncology, University of Washington, Seattle, WA Departments of daggerRadiology double daggerRadiation Oncology section signSurgery, Division of Thoracic Surgery parallelDepartment of Medicine, Division of Pulmonary, Allergy & Critical Care, University of Pennsylvania, Philadelphia, PA. FAU - Pryma, Daniel A AU - Pryma DA FAU - Xanthopoulos, Eric AU - Xanthopoulos E FAU - Kucharczuk, John AU - Kucharczuk J FAU - Sterman, Daniel AU - Sterman D FAU - Rengan, Ramesh AU - Rengan R LA - eng PT - Journal Article PL - United States TA - Am J Clin Oncol JT - American journal of clinical oncology JID - 8207754 RN - 0 (Radiopharmaceuticals) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/mortality/*pathology/*radionuclide imaging MH - Female MH - Fluorodeoxyglucose F18/*diagnostic use/*pharmacokinetics MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/mortality/*pathology/radionuclide imaging MH - Lymph Nodes/*pathology/*radionuclide imaging MH - Male MH - Mediastinum/*pathology/radionuclide imaging MH - Middle Aged MH - Multivariate Analysis MH - Positron-Emission Tomography MH - Predictive Value of Tests MH - Prognosis MH - Radiopharmaceuticals/diagnostic use MH - Retrospective Studies EDAT- 2012/11/01 06:00 MHDA- 2015/05/02 06:00 CRDT- 2012/11/01 06:00 AID - 10.1097/COC.0b013e31826b9cd3 [doi] PST - ppublish SO - Am J Clin Oncol. 2014 Apr;37(2):135-9. doi: 10.1097/COC.0b013e31826b9cd3.