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Journal of Thoracic Oncology

Chee Khoon Lee, Johnathan Man, Sally Lord, Matthew Links, Val Gebski, Tony Mok, James Chih-Hsin Yang
INTRODUCTION: We performed a meta-analysis to assess the role of immune-checkpoint inhibitors as second-line therapy in epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC). METHODS: Randomized trials comparing immune-checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation defined subgroups...
October 17, 2016: Journal of Thoracic Oncology
Alex Herskovic, Elizabeth Mauer, Paul Christos, Himanshu Nagar
BACKGROUND: The role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) non-small cell lung cancer (NSCLC) remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database. METHODS: Patients with known histologies of pathologic stage IIIA (N2) NSCLC who underwent surgery with negative margins and received adjuvant multiagent chemotherapy from 2004-2013 were identified from the National Cancer DataBase (NCDB) and stratified by the use of PORT...
October 13, 2016: Journal of Thoracic Oncology
Christina K Speirs, Todd A DeWees, Sana Rehman, Alerson Molotievschi, Maria A Velez, Daniel Mullen, Sandra Fergus, Marco Trovo, Jeffrey D Bradley, Cliff G Robinson
INTRODUCTION: In the randomized trial of standard vs high dose chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) (RTOG 0617), overall survival (OS) was worse in the high dose arm. While heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters impacting OS in this patient population, focusing on heart dose. METHODS: Clinical data was collected on 416 patients with LA-NSLC treated at a single institution, with a subset of 333 available treatment plans re-contoured using RTOG normal tissue guidelines...
October 12, 2016: Journal of Thoracic Oncology
Stephen G Swisher, Jennifer Moughan, Ritsuko U Komaki, Jaffer A Ajani, Tsung T Wu, Wayne L Hofstetter, Andre A Konski, Christopher G Willett
INTRODUCTION: The impact of selective surgical resection for esophageal cancer patients treated with definitive chemoradiation has not been clearly evaluated long-term. METHODS: NRG Oncology RTOG 0246 was a multi-institutional, single arm, open-label, non-randomized phase II study, which enrolled forty-three patients from Sept 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) from 19 sites...
October 8, 2016: Journal of Thoracic Oncology
Christian Manegold, Anne-Marie C Dingemans, Jhanelle E Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crino, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M Huber, Aurelien Marabelle, Marcin Moniuszko, Francoise Mornex, Silvia Novello, Mauro Papotti, Maurice Pérol, Egbert F Smit, Kostas Syrigos, Jan P van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes
Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab and nintedanib). It is hypothesised that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments...
October 8, 2016: Journal of Thoracic Oncology
Jianlin Xu, Haitang Yang, Xiaolong Fu, Bo Jin, Yuqing Lou, Yanwei Zhang, Xueyan Zhang, Hua Zhong, Huiming Wang, Dan Wu, Baohui Han
INTRODUCTION: Data on prophylactic cranial irradiation (PCI) after complete resection of SCLC are limited. The purpose of this study was to investigate the impact of PCI in this population. METHODS: We retrospectively identified completely resected SCLC at the Shanghai Chest Hospital between January 2006 and January 2014. RESULTS: A total of 349 patients (115 patients who received PCI [the PCI-treated cohort] and 234 patients who did not [the non-PCI-treated cohort]) were included in the study...
October 7, 2016: Journal of Thoracic Oncology
Sarah J Gao, Christopher D Corso, Elyn H Wang, Justin D Blasberg, Frank C Detterbeck, Daniel J Boffa, Roy H Decker, Anthony W Kim
INTRODUCTION: A subset of patients with potentially resectable clinical stage IIIA non-small cell lung cancer (NSCLC) are managed with trimodality therapy. However, little data exist to guide the timing of surgery after neoadjuvant therapy. This study examined whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical resection impacts overall survival. METHODS: Clinical stage IIIA disease (T1-3 N2) NSCLC patients who underwent neoadjuvant chemoradiation therapy were identified in the National Cancer Data Base (NCDB) between 2004-2012 and categorized based on the interval between chemoradiation and surgery (0 to ≤3, 3 to ≤6, 6 to ≤9, and 9 to ≤12 weeks)...
October 5, 2016: Journal of Thoracic Oncology
Sai-Hong Ignatius Ou, Ramaswamy Govindan, Keith D Eaton, Gregory A Otterson, Martin E Gutierrez, Alain C Mita, Athanassios Argiris, Nicoletta M Brega, Tiziana Usari, Weiwei Tan, Steffan N Ho, Francisco Robert
INTRODUCTION: This phase I trial was conducted to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus erlotinib in patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with an Eastern Cooperative Oncology Group performance status of 0-2 after failure of 1-2 prior chemotherapy regimens were eligible. Erlotinib 100 mg was given continuously once daily (QD) starting between day -14 and -7; crizotinib 200 mg twice daily (BID; dose level 1) or 150 mg BID (dose level -1) was added continuously beginning on treatment cycle 1, day 1...
September 30, 2016: Journal of Thoracic Oncology
Shaohua Lu, Kay See Tan, Kyuichi Kadota, Takashi Eguchi, Sarina Bains, Natasha Rekhtman, Prasad S Adusumilli, William D Travis
INTRODUCTION: Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma, however, it has not yet been characterized in squamous cell carcinoma (SCC). METHODS: We reviewed 445 resected stage I-III lung SCC and investigated the clinical significance of STAS. Cumulative incidence of recurrence (CIR) and lung cancer-specific death (CID) were evaluated by competing risks analyses and overall survival (OS) by Cox models. RESULTS: Of total 445 patients, 336 (76%) were >65 years old...
September 28, 2016: Journal of Thoracic Oncology
Valerie W Rusch, Kari Chansky, Hedy L Kindler, Anna K Nowak, Harvey I Pass, David C Rice, Lynn Shemanski, Françoise Galateau-Sallé, Brian C McCaughan, Takashi Nakano, Enrico Ruffini, Jan P van Meerbeeck, Masahiro Yoshimura
INTRODUCTION: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. METHODS: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical M0 (cM0) and cM1 categories...
September 28, 2016: Journal of Thoracic Oncology
Samuel J Klempner, Ali Borghei, Behrooz Hakimian, Siraj M Ali, Sai-Hong Ignatius Ou
INTRODUCTION: A significant portion of non-small cell lung cancers with MET exon14 skipping alterations are sensitive to small molecule MET tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need. METHODS: Hybrid capture based comprehensive genomic profiling identified a patient with a MET exon14 skipping alteration and serial MRI imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy...
September 27, 2016: Journal of Thoracic Oncology
David Rice, Kari Chansky, Anna Nowak, Harvey Pass, Hedy Kindler, Lynn Shemanski, Isabelle Opitz, Sergi Call Caja, Seiki Hasegawa, Kemp Kernstine, Cansel Atinkaya, Federico Rea, Philippe Nafteux, Valerie Rusch
INTRODUCTION: Nodal categories for malignant pleural mesothelioma (MPM) are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer (IASLC) developed a multinational database to generate evidence-based recommendations to inform the 8(th) edition of the tumor, node metastasis classification of MPM. METHODS: Data from 29 centers were entered prospectively (n=1,566) or by transfer of retrospective data (n=1,953)...
September 23, 2016: Journal of Thoracic Oncology
Anna K Nowak, Kari Chansky, David C Rice, Harvey I Pass, Hedy L Kindler, Lynn Shemanski, Andrea Billé, Robert Rintoul, Hasan F Batirel, Charles F Thomas, Joseph Friedberg, Susana Cedres, Marc de Perrot, Valerie W Rusch
INTRODUCTION: Current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical datasets and consensus. The International Association for the Study of Lung Cancer undertook revision of the 7(th) Edition staging system for MPM with the goal of developing recommendations for the 8(th) edition. METHODS: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded...
September 23, 2016: Journal of Thoracic Oncology
Harvey Pass, Dorothy Giroux, Catherine Kennedy, Enrico Ruffini, Ayten K Cangir, David Rice, Hisao Asamura, David Waller, John Edwards, Walter Weder, Hans Hoffmann, Jan P van Meerbeeck, Anna Nowak, Valerie W Rusch
For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma (MPM). In 1994, members of the International Mesothelioma Interest Group (IMIG), in collaboration with the International Association for the Study of Lung Cancer (IASLC), proposed a tumor, node and metastasis (TNM) staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer (AJCC) and the Union for International Cancer Control (UICC) for the 6(th) editions of their staging manuals, this system has since been the international staging standard...
September 23, 2016: Journal of Thoracic Oncology
Sai-Hong Ignatius Ou, Lauren Young, Alexa B Schrock, Adrienne Johnson, Samuel J Klempner, Viola W Zhu, Vincent A Miller, Siraj M Ali
INTRODUCTION: MET exon14 skipping (METex14) alterations represent a unique subset of oncogenic drivers in non-small cell lung cancer (NSCLC). Preliminary clinical activity of crizotinib against METex14+ NSCLC has been reported. The full spectrum of resistance mechanisms to crizotinib in METex14+ NSCLC remains to be identified. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) performed on a tumor specimen obtained at diagnosis and a hybrid capture-based assay of circulating tumor DNA (ctDNA) at the time of progression on crizotinib was assessed in a pairwise fashion...
September 22, 2016: Journal of Thoracic Oncology
Geoffrey B Johnson, Marie Christine Aubry, Eunhee S Yi, Chi Wan Koo, Sarah M Jenkins, Yolanda I Garces, Randolph S Marks, Stephen D Cassivi, Anja C Roden
INTRODUCTION: Neoadjuvant treatment might increase resectability of thymic epithelial tumors (TET). No standardized pathologic grading scheme for tumor response is available. Also, it is unclear whether radiologic treatment response can predict pathologic response. METHODS: Patients with unresectable TET who underwent neoadjuvant treatment before surgery at Mayo Clinic Rochester (1942-2014) were included. The pathologic tumor response grade (TRG) was based upon Mandard-grading (1994) ranging from TRG 1 (no viable tumor) to TRG 5 (no regression)...
September 22, 2016: Journal of Thoracic Oncology
Tzahi Neuman, Michal London, Juliane Kania-Almog, Anna Litvin, Yaniv Zohar, Ludmila Fridel, Judith Sandbank, Iris Barshak, Gilad W Vainer
INTRODUCTION: Immunotherapy is a novel treatment for lung cancer. Pembrolizumab (Merck Sharp and Dohme, Kenilworth, NJ) is a monoclonal antibody against programmed cell death 1 that has been approved for use with NSCLC together with a companion diagnostic by Dako (Carpinteria, CA). Ventana's BenchMark XT (Ventana Medical Systems, Tucson, AZ) is a widely used immunohistochemical (IHC) platform. However, data on its reliability and reproducibility with the 22C3 antibody are scant. METHODS: We performed a comprehensive calibration of 22C3 programmed cell death ligand 1 (PD-L1) staining on the BenchMark XT platform using Dako's prediluted 22C3 anti-PD-L1 primary antibody with two of Ventana's detection systems...
September 21, 2016: Journal of Thoracic Oncology
Rafael Caparica, Cheng Tzu Yen, Renata Coudry, Sai-Hong Ignatius Ou, Marileila Varella-Garcia, D Ross Camidge, Gilberto de Castro
MET activation highly sensitive to MET inhibition has recently been described in non-small cell lung cancer (NSCLC) through two mechanisms: high-level amplification of the MET gene (usually expressed relative to the centromere on chromosome 7 when using fluorescence in-situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other, or if both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor sensitive NSCLC harboring exon 14 alterations without co-incident amplification have already been described...
September 21, 2016: Journal of Thoracic Oncology
Kenichi Suda, Paul A Bunn, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
Diverse molecular mechanisms that confer acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in lung cancers with sensitive EGFR mutations have been reported. However, it is not realistic to analyze for all these mechanisms at the time of resistance in clinical practice and establish adequate treatment targeting these numerous resistance mechanisms. Therefore, we believe that we should move our research focus from the exploration of "established" diverse resistance mechanisms to the elucidation of molecular mechanisms that enable cancer cells to remain alive at the early phase of the treatment...
September 15, 2016: Journal of Thoracic Oncology
Hui Yu, Cory Batenchuk, Andrzej Badzio, Theresa A Boyle, Piotr Czapiewski, Daniel C Chan, Xian Lu, Dexiang Gao, Kim Ellison, Ashley A Kowalewski, Christopher J Rivard, Rafal Dziadziuszko, Caicun Zhou, Maen Hussein, Donald Richards, Sharon Wilks, Marc Monte, William Edenfield, Jerome Goldschmidt, Ray Page, Brian Ulrich, David Waterhouse, Sandra Close, Jacek Jassem, Kimary Kulig, Fred R Hirsch
No abstract text is available yet for this article.
September 14, 2016: Journal of Thoracic Oncology
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