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By Saadvik Raghuram Medical oncologist
https://www.readbyqxmd.com/read/28396313/acquired-met-y1248h-and-d1246n-mutations-mediate-resistance-to-met-inhibitors-in-non-small-cell-lung-cancer
#1
Anna Li, Jin-Ji Yang, Xu-Chao Zhang, Zhou Zhang, Jian Su, Lan-Ying Gou, Yu Bai, Qing Zhou, Zhenfan Yang, Han Han-Zhang, Wen-Zhao Zhong, Shannon Chuai, Qi Zhang, Zhi Xie, Hongfei Gao, Huajun Chen, Zhen Wang, Zheng Wang, Xue-Ning Yang, Bin-Chao Wang, Bin Gan, Zhi-Hong Chen, Ben-Yuan Jiang, Si-Pei Wu, Si-Yang Liu, Chong-Rui Xu, Yi-Long Wu
Purpose:MET amplification, responsible for 20% of acquired resistance to EGFR tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC), presents an attractive target. Numerous studies have conferred susceptibility of MET mutations and focal amplification to targeted MET-TKIs. However, the mechanism underlying MET-TKIs-induced resistance remains elusive.Experimental Design: We conducted a cohort of 12 patients with advanced NSCLC who developed resistance to a combinatorial therapy consisting of gefitinib and a type I MET-TKI...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29232915/histologic-grade-is-predictive-of-incidence-of-epidermal-growth-factor-receptor-mutations-in-metastatic-lung-adenocarcinoma
#2
Michelle Levy, Liisa Lyon, Erika Barbero, John Wong, Marie Suga, Danny Sam, Minggui Pan
Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations...
December 11, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29100447/can-peripheral-blood-be-used-as-surrogate-in-detecting-epidermal-growth-factor-receptor-mutation-status-in-advanced-non-small-cell-lung-cancer-patients-a-meta-analysis
#3
Xiaowei Mao, Yujun Zhang, Fangfang Xie, Xiaoxuan Zheng, Jiayuan Sun
Background: Apply peripheral blood as a surrogate for detecting epidermal growth factor receptor mutation status in tumor, also called liquid biopsy, has been reported to be a feasible method in patients with advanced non-small lung cancer. But the diagnostic yield varies in different studies. Methods: A meta-analysis was carried out to evaluate the sensitivity and specificity of peripheral blood in detection epidermal growth factor receptor mutation status in advanced non-small lung cancer patients...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29164298/value-of-18-f-fdg-pet-ct-for-predicting-egfr-mutations-and-positive-alk-expression-in-patients-with-non-small-cell-lung-cancer-a-retrospective-analysis-of-849-chinese-patients
#4
Zhilei Lv, Jinshuo Fan, Juanjuan Xu, Feng Wu, Qi Huang, Mengfei Guo, Tingting Liao, Shuqing Liu, Xiaoli Lan, Shanshan Liao, Wei Geng, Yang Jin
PURPOSE: Epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) rearrangement are the two most common druggable targets in non-small cell lung cancer (NSCLC). However, genetic testing is sometimes unavailable. Previous studies regarding the predictive role of (18)F-FDG PET/CT for EGFR mutations in NSCLC patients are conflicting. We investigated whether or not (18)F-FDG PET could be a valuable noninvasive method to predict EGFR mutations and ALK positivity in NSCLC using the largest patient cohort to date...
November 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#5
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
October 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28885881/durvalumab-after-chemoradiotherapy-in-stage-iii-non-small-cell-lung-cancer
#6
RANDOMIZED CONTROLLED TRIAL
Scott J Antonia, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, Alberto Chiappori, Ki H Lee, Maike de Wit, Byoung C Cho, Maryam Bourhaba, Xavier Quantin, Takaaki Tokito, Tarek Mekhail, David Planchard, Young-Chul Kim, Christos S Karapetis, Sandrine Hiret, Gyula Ostoros, Kaoru Kubota, Jhanelle E Gray, Luis Paz-Ares, Javier de Castro Carpeño, Catherine Wadsworth, Giovanni Melillo, Haiyi Jiang, Yifan Huang, Phillip A Dennis, Mustafa Özgüroğlu
BACKGROUND: Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months...
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28137739/etoposide-and-cisplatin-versus-paclitaxel-and-carboplatin-with-concurrent-thoracic-radiotherapy-in-unresectable-stage-iii-non-small-cell-lung-cancer-a-multicenter-randomized-phase-iii-trial
#7
RANDOMIZED CONTROLLED TRIAL
J Liang, N Bi, S Wu, M Chen, C Lv, L Zhao, A Shi, W Jiang, Y Xu, Z Zhou, W Wang, D Chen, Z Hui, J Lv, H Zhang, Q Feng, Z Xiao, X Wang, L Liu, T Zhang, L Du, W Chen, Y Shyr, W Yin, J Li, J He, L Wang
Background: The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods: Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm)...
April 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27393514/advanced-non-small-cell-lung-cancer-patients-at-the-extremes-of-age-in-the-era-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#8
Yu-Mu Chen, Chien-Hao Lai, Kun-Ming Rau, Cheng-Hua Huang, Huang-Chih Chang, Tung-Ying Chao, Chia-Cheng Tseng, Wen-Feng Fang, Yung-Che Chen, Yu-Hsiu Chung, Yi-Hsi Wang, Mao-Chang Su, Kuo-Tung Huang, Shih-Feng Liu, Hung-Chen Chen, Ya-Chun Chang, Yu-Ping Chang, Chin-Chou Wang, Meng-Chih Lin
OBJECTIVES: The clinical characteristics and survival of very young (≤40 years) and very old (>80years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients' clinical characteristics and prognosis. MATERIALS AND METHODS: Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included...
August 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27223332/first-line-treatment-of-advanced-epidermal-growth-factor-receptor-egfr-mutation-positive-non-squamous-non-small-cell-lung-cancer
#9
REVIEW
Janette Greenhalgh, Kerry Dwan, Angela Boland, Victoria Bates, Fabio Vecchio, Yenal Dundar, Pooja Jain, John A Green
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is emerging as an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men and is less associated with smoking. OBJECTIVES: To assess the clinical effectiveness of single -agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC)...
May 25, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27189523/impact-of-heart-and-lung-dose-on-early-survival-in-patients-with-non-small-cell-lung-cancer-treated-with-chemoradiation
#10
Susan L Tucker, Anwen Liu, Daniel Gomez, Ling Long Tang, Pamela Allen, Jinzhong Yang, Zhongxing Liao, David Grosshans
BACKGROUND AND PURPOSE: To determine whether the impact of heart dose on early overall survival (OS) reported in RTOG 0617 could be confirmed in an independent cohort. MATERIALS AND METHODS: Heart and lung dose-volume histogram data were retrospectively extracted for patients with stage IIIA-IIIB non-small cell lung cancer (NSCLC) who had received radiotherapy using 3D CRT, IMRT or proton therapy delivered with concurrent chemotherapy between 1999 and 2010. Potential associations between clinical and dosimetric factors and OS up to 24months after start of treatment were assessed in univariate and multivariate analyses with log-rank tests or Cox proportional hazards models...
June 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27186518/erlotinib-plus-concurrent-whole-brain-radiation-therapy-for-non-small-cell-lung-cancers-patients-with-multiple-brain-metastases
#11
Danny Ulahannan, Siow-Ming Lee
Sequencing of the epidermal growth factor receptor (EGFR) gene to identify mutations in lung adenocarcinomas is routine in clinical practice. The use of tyrosine kinase inhibitors (TKIs) has transformed the management of patients with brain metastases harboring EGFR mutations, with improved response rates (RR) and survival. We evaluate the role of concurrent TKI therapy and radiotherapy in this group of patients, considering this data in the context of emerging concepts in this advancing field.
April 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27106020/targeted-therapy-combined-with-radiotherapy-in-non-small-cell-lung-cancer-a-review-of-the-oncologic-group-for-the-study-of-lung-cancer-spanish-radiation-oncology-society
#12
REVIEW
F Couñago, A Rodríguez, P Calvo, J Luna, J L Monroy, B Taboada, V Díaz, N Rodríguez de Dios
In recent years, major advances in our understanding of the molecular biology of lung cancer, together with significant improvements in radiotherapy technologies, have revolutionized the treatment of non-small cell lung cancer (NSCLC). This has led to the development of new therapies that target molecular mutations specific to each tumor type, acting on the cell surface antigens or intracellular signaling pathways, or directly affecting cell survival. At the same time, ablative dose radiotherapy can be delivered safely in the context of metastatic disease...
January 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27044418/quantification-of-the-smoking-associated-cancer-risk-with-rate-advancement-periods-meta-analysis-of-individual-participant-data-from-cohorts-of-the-chances-consortium
#13
José Manuel Ordóñez-Mena, Ben Schöttker, Ute Mons, Mazda Jenab, Heinz Freisling, Bas Bueno-de-Mesquita, Mark G O'Doherty, Angela Scott, Frank Kee, Bruno H Stricker, Albert Hofman, Catherine E de Keyser, Rikje Ruiter, Stefan Söderberg, Pekka Jousilahti, Kari Kuulasmaa, Neal D Freedman, Tom Wilsgaard, Lisette Cpgm de Groot, Ellen Kampman, Niclas Håkansson, Nicola Orsini, Alicja Wolk, Lena Maria Nilsson, Anne Tjønneland, Andrzej Pająk, Sofia Malyutina, Růžena Kubínová, Abdonas Tamosiunas, Martin Bobak, Michail Katsoulis, Philippos Orfanos, Paolo Boffetta, Antonia Trichopoulou, Hermann Brenner
BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality...
April 5, 2016: BMC Medicine
https://www.readbyqxmd.com/read/26150526/egfr-inhibition-evokes-innate-drug-resistance-in-lung-cancer-cells-by-preventing-akt-activity-and-thus-inactivating-ets-1-function
#14
Janyaporn Phuchareon, Frank McCormick, David W Eisele, Osamu Tetsu
Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. About 14% of NSCLCs harbor mutations in epidermal growth factor receptor (EGFR). Despite remarkable progress in treatment with tyrosine kinase inhibitors (TKIs), only 5% of patients achieve tumor reduction >90%. The limited primary responses are attributed partly to drug resistance inherent in the tumor cells before therapy begins. Recent reports showed that activation of receptor tyrosine kinases (RTKs) is an important determinant of this innate drug resistance...
July 21, 2015: Proceedings of the National Academy of Sciences of the United States of America
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