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Journal of Thoracic Oncology

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https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#1
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28189832/characteristics-and-outcomes-of-patients-with-lung-cancer-harboring-multiple-molecular-alterations-results-from-the-ifct-study-biomarkers-france
#2
Nicolas Guibert, Fabrice Barlesi, Renaud Descourt, Hervé Léna, Benjamin Besse, Michèle Beau-Faller, Jean Mosser, Eric Pichon, Jean-Philippe Merlio, L'Houcine Ouafik, François Guichard, Bénédicte Mastroianni, Lionel Moreau, Annie Wdowik, Jean-Christophe Sabourin, Antoinette Lemoine, Pascale Missy, Alexandra Langlais, Denis Moro-Sibilot, Julien Mazieres
INTRODUCTION: Little is known about the prevalence, prognosis and response to treatment of advanced non-small cell lung cancer (NSCLC) harboring multiple genomic alterations. METHODS: The French Biomarkers France database (IFCT) including 17,664 patients was used. The prevalence of multiple alterations, their associations, impact on prognosis (overall survival: OS) and their response to targeted or conventional treatments (progression free survival: PFS; objective response rate: ORR), were assessed and compared with those of patients harboring single or no mutation...
February 9, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28179162/loss-of-p16-ink4a-expression-and-homozygous-cdkn2a-deletion-are-associated-with-worse-outcome-and-younger-age-in-thymic-carcinomas
#3
Scott W Aesif, Marie Christine Aubry, Eunhee S Yi, Sara M Kloft-Nelson, Sarah M Jenkins, Grant M Spears, Patricia T Greipp, William R Sukov, Anja C Roden
PURPOSE: Thymic carcinomas are aggressive tumors. Biomarkers and alternative treatment modalities are needed. We studied the expression of p16 and cytogenetic abnormalities of CDKN2A and correlated findings with clinical features and outcome in a large cohort of thymic carcinomas. MATERIALS AND METHODS: Thymic carcinomas (1963-2013) were stained with p16. Fluorescence in situ hybridization was utilized to assess for the presence of CDKN2A gene (at 9p21). Statistical analysis was performed...
February 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28167203/erbb2-mutated-metastatic-non-small-cell-lung-cancer-response-and-resistance-to-targeted-therapies
#4
Jody C Chuang, Henning Stehr, Ying Liang, Millie Das, Jane Huang, Maximilian Diehn, Heather A Wakelee, Joel W Neal
ERBB2/HER2 has long been recognized as an oncogenic driver in some breast and gastro-esophageal cancers, in which amplification of this gene confers sensitivity to treatment with ERBB2 directed agents. More recently, somatic mutations in ERBB2 have been reported in 1-2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies. Here we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2 targeted therapies...
February 3, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28161554/maintenance-sunitinib-following-initial-platinum-based-combination-chemotherapy-in-advanced-stage-iiib-iv-non-small-cell-lung-cancer-a-randomized-double-blind-placebo-controlled-phase-iii-study-calgb-30607-alliance
#5
Maria Q Baggstrom, Mark A Socinski, Xiaofei F Wang, Lin Gu, Thomas E Stinchcombe, Martin J Edelman, Sherman Baker, Josephine Feliciano, Paul Novotny, Olwen Hahn, Jeffrey A Crawford, Everett E Vokes
INTRODUCTION: To evaluate efficacy of maintenance sunitinib after first-line chemotherapy for stage IIIB/IV non-small cell lung cancer (NSCLC). METHODS: Cancer and Leukemia Group B (CALGB) 30607 trial was a randomized, double-blind, placebo-controlled, phase III study that enrolled patients without progression after four cycles of first-line platinum-based doublet chemotherapy with or without bevacizumab. Bevacizumab was only allowed during the four cycles of chemotherapy...
February 1, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28214559/radiation-therapy-for-invasive-breast-cancer-increases-the-risk-of-second-primary-lung-cancer-a-nationwide-population-based-cohort-analysis
#6
Yi-Jhih Huang, Tsai-Wang Huang, Fu-Huang Lin, Chi-Hsiang Chung, Chang-Huei Tsao, Wu-Chien Chien
INTRODUCTION: Although the risk factors for lung cancer are well documented, it remains unclear if previous radiation therapy (RT) to treat breast cancer (BC) increases the incidence of second primary lung cancer. We determined the overall incidence of second primary lung cancer after previous RT for all clinical stages of BC. METHODS: After analyzing the Longitudinal Health Insurance Database, 986,713 individuals were randomly enrolled from 2000 to 2010 for cohort analysis...
January 31, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28147239/a-sensitive-alk-immunohistochemistry-companion-diagnostic-test-identifies-patients-eligible-for-treatment-with-crizotinib
#7
Trish Thorne-Nuzzo, Crystal Williams, Alice Catallini, June Clements, Shalini Singh, James Amberson, Kim Dickinson, Zoran Gatalica, Steffan N Ho, Isabell Loftin, Abigail McElhinny, Penny Towne
INTRODUCTION: The availability of high quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK) NSCLC who can potentially benefit from treatment with crizotinib. Here we present data on the recently approved VENTANA ALK (D5F3) CDx Assay (ALK (D5F3) CDx), the only immunohistochemistry (IHC) based assay linked to treatment outcome. METHODS: NSCLC specimens prospectively tested for ALK status by Flourescent In-situ Hybridization (FISH) in the PROFILE 1014 clinical trial of crizotinib versus chemotherapy (N=1018, including 179 ALK(+) and 754 ALK(-) specimens), were evaluated using the ALK (D5F3) CDx assay...
January 29, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28132868/lag-3-protein-expression-in-non-small-cell-lung-cancer-and-its-relationship-with-pd-1-pd-l1-and-tumor-infiltrating-lymphocytes
#8
Yayi He, Hui Yu, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Kenichi Suda, Shengxiang Ren, Chunyan Wu, Likun Hou, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy targeting the programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) checkpoint has shown promising efficacy in patients with non-small cell lung cancer (NSCLC). Lymphocyte activation gene-3 (LAG-3) is another important checkpoint, and its role in NSCLC is still not clear. In this study, we investigated LAG-3 protein expression and its correlation with PD-1, PD-L1, tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. METHODS: The expression of LAG-3 (EPR4392, Abcam) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC)...
January 26, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28126540/the-impact-of-postoperative-radiotherapy-for-thymoma-and-thymic-carcinoma
#9
Matthew W Jackson, David A Palma, D Ross Camidge, Bernard L Jones, Tyler P Robin, David J Sher, Matthew Koshy, Brian D Kavanagh, Laurie E Gaspar, Chad G Rusthoven
INTRODUCTION: The optimal role for postoperative radiation therapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Database to investigate the impact of PORT on overall survival. METHODS: Patients who underwent surgery for thymoma or thymic carcinoma were categorized into Masaoka-Koga stage groups I-IIA, IIB, III, and IV. Patients who did not undergo surgery or those who received preoperative radiation were excluded. Kaplan-Meier OS estimates, univariate (UVA) and multivariate (MVA) Cox proportional hazards regression analyses were performed...
January 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28126539/regional-emphysema-score-predicting-overall-survival-quality-of-life-and-pulmonary-function-recovery-in-early-stage-lung-cancer-patients
#10
Jie Dai, Ming Liu, Stephen J Swensen, Shawn M Stoddard, Jason A Wampfler, Andrew H Limper, Gening Jiang, Ping Yang
INTRODUCTION: Pulmonary emphysema is a common comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on patient's overall survival, quality of life (QOL), and pulmonary function recovery in stage I-II lung cancer. METHODS: Between 1997 and 2009, 1,073 patients were identified and divided into two surgical groups (cancer in emphysematous [group 1, n=565] and non-emphysematous [group 2, n=435] region) and one non-surgical group (group 3, n=73)...
January 23, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28126538/rethinking-autoantibody-signature-panels-for-cancer-diagnosis-a-brief-report
#11
Michael J Campa, Elizabeth B Gottlin, James E Herndon, Edward F Patz
INTRODUCTION: Most pulmonary nodules found on imaging studies are indeterminate, but because of the concern for lung cancer, all patients require further evaluation with resultant radiation risk, significant cost and delays in diagnosis. We hypothesized that a diagnostic blood test based on detection of autoantibodies against cancer antigens would be able to distinguish a benign nodule from lung cancer. METHODS: We identified a panel of 25 serum autoantibodies associated with NSCLC and constructed a protein microarray containing the autoantigens...
January 23, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28111235/comparison-of-segmentectomy-and-lobectomy-in-stage-ia-adenocarcinomas-1-and-%C3%A2-2-cm-a-brief-report
#12
Ze-Rui Zhao, Dong-Rong Situ, Rainbow W H Lau, Tony S K Mok, George G Chen, Malcolm J Underwood, Calvin S H Ng
INTRODUCTION: Recent studies have suggested that segmentectomy may be an acceptable alternative treatment to lobectomy, for surgical management of smaller lung adenocarcinomas. The objective of this study was to compare survival after lobectomy and segmentectomy among patients with pathological stage IA adenocarcinoma categorized as the new T1b (>10 to ≤20 mm) according to the eighth TNM system. METHODS: In total, 7,989 patients were identified from the Surveillance, Epidemiology, and End Results registry...
January 19, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28108303/braf-v600e-mutation-is-not-always-present-as-expected-a-case-report-of-lung-and-thyroid-carcinomas
#13
Nicolas Piton, Mathieu Salaün, Florian Guisier, Florent Marguet, Emmanuel K Touré, Pierre Gémival, Luc Thiberville, Jean-Christophe Sabourin
No abstract text is available yet for this article.
January 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#14
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1(st)-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28104536/exome-wide-association-study-identifies-low-frequency-coding-variants-in-2p23-2-and-7p11-2-associated-with-survival-of-non-small-cell-lung-cancer-patients
#15
Meng Zhu, Liguo Geng, Wei Shen, Yuzhuo Wang, Jia Liu, Yang Cheng, Cheng Wang, Juncheng Dai, Guangfu Jin, Zhibin Hu, Hongxia Ma, Hongbing Shen
INTRODUCTION: A growing body of evidence has suggested that low-frequency or rare variants might have strong effects on the development and prognosis of cancer. Here, we aim to assess the role of low-frequency and rare coding variants in the survival of non-small cell lung cancer (NSCLC) in Chinese populations. METHODS: We performed an exome-wide scan of 247,870 variants in 1,008 NSCLC patients and replicated the promising variants by using imputed genotype data of The Cancer Genome Atlas (TCGA) with a cox regression model...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in%C3%A2-advanced-nsclc
#16
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
No abstract text is available yet for this article.
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28089762/long-terms-results-of-a-trial-of-concurrent-chemotherapy-and-escalating-doses-of-radiation-for-unresectable-non-small-cell-lung-cancer-ncctg-n0028-alliance
#17
Steven E Schild, Shauna L Hillman, Angelina D Tan, Helen J Ross, William L McGinnis, Yolanda A Garces, David L Graham, Alex A Adjei, James R Jett
INTRODUCTION OR HYPOTHESIS: This phase I/II trial was originally designed to determine the maximally tolerated dose(MTD) of thoracic radiotherapy(TRT) as part of a combined modality approach. This report includes the long-term outcome of patients treated on this study. The phase II portion was never completed as RTOG-0617 opened before it was concluded. METHODS: The MTD was defined as 74Gy in 37 fractions in this study. Twenty-five patients with unresectable non-small cell lung cancer(NSCLC) were treated with 2Gy daily fractions and concurrent weekly carboplatin and paclitaxel...
January 12, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#18
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing. METHODS: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#19
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the gene ROS1 define a distinct molecular subset of NSCLCs with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in EGFR and KRAS. METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma receptor tyrosine kinase gene (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#20
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
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