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https://www.readbyqxmd.com/read/28816950/pemetrexed-carboplatin-with-intercalated-icotinib-in-the-treatment-of-patient-with-advanced-egfr-wild-type-lung-adenocarcinoma-a-case-report
#1
Tongpeng Xu, Hao Wu, Shidai Jin, Huang Min, Zhihong Zhang, Yongqian Shu, Wei Wen, Renhua Guo
RATIONALE: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. PATIENT CONCERNS: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. DIAGNOSES: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28814805/intercalating-and-maintenance-gefitinib-plus-chemotherapy-versus-chemotherapy-alone-in-selected-advanced-non-small-cell-lung-cancer-with-unknown-egfr-status
#2
Hong Jian, Wei Li, Zhiyong Ma, Jianjin Huang, Jifeng Feng, Yong Song, Beili Gao, Huili Zhu, Min Tao, Chong Bai, Shenglin Ma, Hongming Pan, Shukui Qin, Dong Hua, Yongfeng Yu, Shun Lu
Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m(2)) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15-25 of each cycle until disease progress (n = 109)...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#3
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#4
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28807247/interleukins-as-new-prognostic-genetic-biomarkers-in-non-small-cell-lung-cancer
#5
Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Ahmed Alnatsha, Miguel Ángel Molina, Ana I Robles, Eduardo Villar, Juan Ramón Delgado, María José Faus-Dáder, Miguel Ángel Calleja-Hernández
BACKGROUND: Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28807234/third-generation-egfr-tkis-in-egfr-mutated-nsclc-where-are-we-now-and-where-are-we-going
#6
REVIEW
A Russo, T Franchina, G R R Ricciardi, V Smiroldo, M Picciotto, M Zanghì, C Rolfo, V Adamo
The therapeutic landscape of Non Small Lung Cancer (NSCLC) has been profoundly changed over the last decade with the clinical introduction of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) and the discovery of EGFR activating mutations as the major predictive factor to these agents. Despite impressive clinical activity against EGFR-mutated NSCLCs, the benefit seen with 1st and 2nd generation EGFR TKIs is usually transient and virtually all patients become resistant. Several different mechanisms of acquired resistance have been reported to date, but the vast majority of patients develop a secondary exon 20 mutation in the ATP-binding site of EGFR, namely T790M...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806935/association-between-charlson-comorbidity-index-score-and-outcome-in-patients-with-stage-iiib-iv-non-small-cell-lung-cancer
#7
Lei Zhao, Lai-Han Leung, Jing Wang, Huihui Li, Juanjuan Che, Lian Liu, Xiaojun Yao, Bangwei Cao
BACKGROUND: This retrospective study investigated the association between the Charlson comorbidity index (CCI) score and the survival of patients with stage IIIB-IV (advanced, non-resectable) non-small cell lung cancer (NSCLC) who also did not have gene mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). METHODS: The records of 165 patients (28-80 y, median 61 y) who met the above criteria and were admitted to Beijing Friendship Hospital Capital Medical University from 1 May 2010 to 1 October 2014were reviewed...
August 15, 2017: BMC Pulmonary Medicine
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
#8
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...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#9
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#10
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#11
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#12
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28790845/clinical-efficacy-evaluation-of-tyrosine-kinase-inhibitors-for-non-adenocarcinoma-lung-cancer-patients-harboring-egfr-sensitizing-mutations
#13
REVIEW
Xinyu Song, Zhehai Wang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28781309/congestive-heart-failure-during-osimertinib-treatment-for-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#14
Hiromi Watanabe, Eiki Ichihara, Hirohisa Kano, Kiichiro Ninomiya, Mitsune Tanimoto, Katsuyuki Kiura
We herein report a case of congestive heart failure which developed during osimertinib treatment. A 78-year-old woman presented with mild exertional dyspnea three weeks after starting osimertinib for the treatment of epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer. She was diagnosed with congestive heart failure caused by the osimertinib. In contrast to trastuzumab, a human epidermal growth factor receptor 2 (HER2) monoclonal antibody that often causes cardiac dysfunction, the causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear...
August 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28780743/high-probability-and-frequency-of-egfr-mutations-in-non-small-cell-lung-cancer-with-brain-metastases
#15
Mengxi Ge, Yingjie Zhuang, Xinli Zhou, Ruofan Huang, Xiaohua Liang, Qiong Zhan
Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction...
August 5, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28779874/brief-report-met-exon-14-alterations-and-new-resistance-mutations-to-tyrosine-kinase-inhibitors-risk-of-inadequate-detection-with-current-amplicon-based-ngs-panels
#16
Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
INTRODUCTION: Targeted therapies, as tyrosine kinase inhibitors (TKI), have dramatically improved the treatment of lung adenocarcinoma and detection of activating mutations of genes like EGFR or ALK is now mandatory in clinical setting. However, additional targetable alterations are continuously described and force us to adapt our detection methods. We evaluate here the ability of 8 amplicon-based next generation sequencing (NGS) panels to detect the recently described MET exon 14 alterations or new resistance-mutations to TKI...
August 2, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28778092/epidermal-growth-factor-receptor-t790m-mutation-as-a-prognostic-factor-in-egfr-mutant-non-small-cell-lung-cancer-patients-that-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors
#17
Guangzhi Ma, Jing Zhang, Hai Jiang, Nannan Zhang, Liyuan Yin, Wen Li, Qinghua Zhou
Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression...
July 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777825/beyond-disease-progression-clinical-outcomes-after-egfr-tkis-in-a-cohort-of-egfr-mutated-nsclc-patients
#18
Roxana Alina Tudor, Adrijana D'Silva, Alain Tremblay, Paul MacEachern, Don Morris, Darren Brenner, Karen Kopciuk, Dafydd Gwyn Bebb
PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28776568/clinical-analysis-of-nsclc-patients-reveals-lack-of-association-between-egfr-mutation-and-tet1-downregulation
#19
J-I Lai, Y-C Lai, Y-C Chen, N-K Wang, J-N Pan, W-S Wang, S-C Chang
Lung cancer is one of the leading causes of death from cancer worldwide, with a poor prognosis in advanced cases. In the past decade, epidermal growth factor receptor (EGFR) inhibitors have shown significant efficacy towards treatment for EGFR mutant lung cancer. Expanding our knowledge of oncogenic EGFR signaling pathways is therefore of highly importance for the cancer field. Recently it has been proposed that mutant EGFR transcriptionally silences the TET1 (ten-eleven translocation methylcytosine dioxygenase 1) gene in cellular and animal models of lung cancer...
August 4, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28776311/continued-egfr-tki-with-concurrent-radiotherapy-to-improve-time-to-progression-ttp-in-patients-with-locally-progressive-non-small-cell-lung-cancer-nsclc-after-front-line-egfr-tki-treatment
#20
Y Wang, Y Li, L Xia, K Niu, X Chen, D Lu, R Kong, Z Chen, J Sun
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. METHODS: Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression...
August 3, 2017: Clinical & Translational Oncology
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