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https://www.readbyqxmd.com/read/29130105/tumor-molecular-profiling-of-nsclc-patients-using-next-generation-sequencing
#1
Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Aikaterini Scapeti, Eugenia Bourkoula, Pavlos Zarogoulidis, George Pentheroudakis, Stylianos Kakolyris, Ioannis Boukovinas, Pavlos Papakotoulas, Elias Athanasiadis, Theofanis Floros, Anna Koumarianou, Vasileios Barbounis, Anca Dinischiotu, George Nasioulas
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29129443/adjuvant-chemotherapy-with-or-without-bevacizumab-in-patients-with-resected-non-small-cell-lung-cancer-e1505-an-open-label-multicentre-randomised-phase-3-trial
#2
Heather A Wakelee, Suzanne E Dahlberg, Steven M Keller, William J Tester, David R Gandara, Stephen L Graziano, Alex A Adjei, Natasha B Leighl, Seena C Aisner, Jan M Rothman, Jyoti D Patel, Mark D Sborov, Sean R McDermott, Roman Perez-Soler, Anne M Traynor, Charles Butts, Tracey Evans, Atif Shafqat, Andrew E Chapman, Samer S Kasbari, Leora Horn, Suresh S Ramalingam, Joan H Schiller
BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#3
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29123418/evaluating-the-cost-effectiveness-of-afatinib-after-platinum-based-therapy-for-the-treatment-of-squamous-non-small-cell-lung-cancer-in-france
#4
Maud Pignata, Christos Chouaid, Katell Le Lay, Laura Luciani, Ceilidh McConnachie, James Gordon, Stéphane Roze
Background and aims: Lung cancer has the highest mortality rate of all cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and has an extremely poor prognosis. Afatinib is an irreversible ErbB family blocker designed to suppress cellular signaling and inhibit cellular growth and is approved in Europe after platinum-based therapy for squamous NSCLC. The objective of the present analysis was to evaluate the cost-effectiveness of afatinib after platinum-based therapy for squamous NSCLC in France...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29119148/brigatinib-for-the-treatment-of-alk-positive-advanced-non-small-cell-lung-cancer-patients
#5
A Passaro, A Prelaj, A Pochesci, G Spitaleri, G Rossi, E Del Signore, C Catania, F de Marinis
Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease...
August 2017: Drugs of Today
https://www.readbyqxmd.com/read/29116951/induction-therapies-plus-surgery-versus-exclusive-radiochemotherapy-in-stage-iiia-n2-non-small-cell-lung-cancer-nsclc
#6
Branislav Jeremić
In spite of the growing body of data from prospective randomized clinical trials (PRCTs) and meta-analyses, the optimal treatment approach in patients with stage IIIA non-small cell lung cancer remains unknown. This review focuses on the available data directly confronting induction chemotherapy or induction radiochemotherapy (RT-CHT) when followed by surgery with exclusive RT-CHT. Seven PRCTs and 4 meta-analyses investigated this issue. In addition, numerous retrospective studies attempted to identify potential predictors and/or prognosticators that may have influenced the decision to offer surgery in a particular patient subgroup...
November 7, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29115057/smoking-and-egfr-status-may-predict-outcomes-of-advanced-nsclc-treated-with-pd-l-1-inhibitors-beyond-first-line-a-meta-analysis
#7
Omar Abdel-Rahman
OBJECTIVES: To assess the potential clinical and biological predictive markers of survival in pretreated advanced NSCLC patients treated with the three PD-(L)1 inhibitors (nivolumab, pembrolizumab, atezolizumab). Data source/ study selection: PubMed database has been searched. The review author extracted relevant information on participant characteristics and study outcomes for this review and assessed risk of bias of the included trials. Data analysis was conducted through RevMan v.5...
November 8, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/29110849/continued-use-of-afatinib-with-the-addition-of-cetuximab-after-progression-on-afatinib-in-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-and-acquired-resistance-to-gefitinib-or-erlotinib
#8
Leora Horn, Scott Gettinger, D Ross Camidge, Egbert F Smit, Yelena Y Janjigian, Vincent A Miller, William Pao, Matthias Freiwald, Jean Fan, Bushi Wang, Vikram K Chand, Harry J M Groen
OBJECTIVES: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. MATERIALS AND METHODS: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m(2) every 2 weeks until progression or intolerable adverse events (AEs)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110837/the-burden-of-neutropenic-sepsis-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-single-agent-docetaxel-a-retrospective-study
#9
Toby Talbot, Adam Dangoor, Riyaz Shah, Jay Naik, Denis Talbot, Jason F Lester, Riccardo Cipelli, Matt Hodgson, Ajay Patel, Max Summerhayes, Thomas Newsom-Davis
OBJECTIVES: To describe rates of confirmed and suspected neutropenic sepsis (NS) and associated hospital resource utilisation in patients with non-small cell lung cancer (NSCLC) treated with docetaxel monotherapy following relapse after ≥1 line of chemotherapy in routine UK clinical practice. MATERIALS AND METHODS: A multi-centre, retrospective, observational research study was conducted in seven centres across England and Wales. Adult patients with stage III/IV NSCLC initiated on docetaxel monotherapy between 2010 and 2016 in routine clinical practice (aged ≥18 years at initiation) following failure of first-line chemotherapy were eligible...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29106810/stereotactic-body-radiotherapy-for-early-stage-non-small-cell-lung-cancer-american-society-of-clinical-oncology-endorsement-of-the-american-society-for-radiation-oncology-evidence-based-guideline
#10
Bryan J Schneider, Megan E Daly, Erin B Kennedy, Mara B Antonoff, Stephen Broderick, Jill Feldman, Shruti Jolly, Bryan Meyers, Gaetano Rocco, Chad Rusthoven, Ben J Slotman, Daniel H Sterman, Brendon M Stiles
Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on treatment with stereotactic body radiotherapy (SBRT) for patients with early-stage non-small-cell lung cancer. ASCO has a policy and set of procedures for endorsing and/or adapting clinical practice guidelines that have been developed by other professional organizations. Methods The ASTRO Evidence-Based Guideline for Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer was reviewed for developmental rigor by methodologists...
November 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29101057/cost-effectiveness-of-osimertinib-for-egfr-mutation-positive-non-small-cell-lung-cancer-after-progression-of-first-line-egfr-tki-therapy
#11
Bin Wu, Xiaohua Gu, Qiang Zhang
INTRODUCTION: To investigate the cost-effectiveness of osimertinib for the treatment of advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) T790M mutation after the failure of first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS: A mathematical model was established by combining a decision tree and the Markov approach to project the cost-effectiveness of osimertinib for the treatment of patients who harbor an EGFR T790M mutation compared to that of standard chemotherapy, who had disease progression after first-line EGFR-TKI therapy with or without metastases to the central nervous system...
October 31, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29100279/radiotherapy-prolongs-the-survival-of-advanced-non-small-cell-lung-cancer-patients-undergone-to-an-immune-modulating-treatment-with-dose-fractioned-cisplatin-and-metronomic-etoposide-and-bevacizumab-mpebev
#12
Pierpaolo Pastina, Valerio Nardone, Cirino Botta, Stefania Croci, Paolo Tini, Giuseppe Battaglia, Veronica Ricci, Maria Grazia Cusi, Claudia Gandolfo, Gabriella Misso, Silvia Zappavigna, Michele Caraglia, Antonio Giordano, Donatella Aldinucci, Pierfrancesco Tassone, Pierosandro Tagliaferri, Luigi Pirtoli, Pierpaolo Correale
Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growth-factor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097733/discovery-of-targetable-genetic-alterations-in-advanced-non-small-cell-lung-cancer-using-a-next-generation-sequencing-based-circulating-tumor-dna-assay
#13
Helei Hou, Xiaonan Yang, Jinping Zhang, Zhe Zhang, Xiaomei Xu, Xiaoping Zhang, Chuantao Zhang, Dong Liu, Weihua Yan, Na Zhou, Hongmei Zhu, Zhaoyang Qian, Zhuokun Li, Xiaochun Zhang
Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097074/a-phase-ii-toxicity-end-point-trial-icorg-99-09-of-accelerated-dose-escalated-hypofractionated-radiation-in-non-small-cell-lung-cancer
#14
D N Cagney, P G Thirion, M T Dunne, C Fleming, D Fitzpatrick, C M O'Shea, M A Finn, S O'Sullivan, C Booth, C D Collins, S J Buckney, A Shannon, J G Armstrong
AIMS: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial...
October 30, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29095090/pharmacokinetic-drug-evaluation-of-osimertinib-for-the-treatment-of-non-small-cell-lung-cancer
#15
Antonio Rossi, Lucia Anna Muscarella, Concetta Di Micco, Cristiano Carbonelli, Vito D'alessandro, Stefano Notarangelo, Giuseppe Palomba, Gerardo Sanpaolo, Marco Taurchini, Paolo Graziano, Evaristo Maiello
First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9-13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene...
November 12, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29090407/pkpd-modeling-of-acquired-resistance-to-anti-cancer-drug-treatment
#16
Miro J Eigenmann, Nicolas Frances, Thierry Lavé, Antje-Christine Walz
Non-small cell lung cancer (NSCLC) patients greatly benefit from the treatment with tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR). However, emergence of acquired resistance inevitable occurs after long-term treatment in most patients and limits clinical improvement. In the present study, resistance to drug treatment in patient-derived NSCLC xenograft mice was assessed and modeling and simulation was applied to understand the dynamics of drug resistance as a basis to explore more beneficial drug regimen...
October 31, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29082855/comparative-efficacy-and-safety-of-second-line-treatments-for-advanced-non-small-cell-lung-cancer-with-wild-type-or-unknown-status-for-epidermal-growth-factor-receptor-a-systematic-review-and-network-meta-analysis
#17
Perrine Créquit, Anna Chaimani, Amélie Yavchitz, Nassima Attiche, Jacques Cadranel, Ludovic Trinquart, Philippe Ravaud
BACKGROUND: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis...
October 30, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29079636/alk-fusions-in-a-wide-variety-of-tumor-types-respond-to-anti-alk-targeted-therapy
#18
Jeffrey S Ross, Siraj M Ali, Omotayo Fasan, Jared Block, Sumanta Pal, Julia A Elvin, Alexa B Schrock, James Suh, Sahar Nozad, Sungeun Kim, Hwa Jeong Lee, Christine E Sheehan, David M Jones, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, Vince A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: Genomic fusions of the anaplastic lymphoma kinase gene (ALK) are a well-established therapy target in non-small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of ALK rearrangements (rALK) in non-NSCLC tumors and report their responsiveness to therapies targeting ALK. MATERIALS AND METHODS: Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay...
October 27, 2017: Oncologist
https://www.readbyqxmd.com/read/29079040/overall-survival-analysis-and-characterization-of-an-egfr-mutated-non-small-cell-lung-cancer-nsclc-population
#19
Filipa Aguiar, Gabriela Fernandes, Henrique Queiroga, José Carlos Machado, Luís Cirnes, Conceição Souto Moura, Venceslau Hespanhol
BACKGROUND: Patients with activating somatic mutations in the Epidermal Growth Factor Receptor (EGFR) have better clinical outcomes when treated with Tyrosine Kinase Inhibitors (TKI) over chemotherapy. However, the impact of the use of TKIs on overall survival outside clinical trials is not well established. OBJECTIVE: To characterize and analyze the overall survival of a Caucasian population with NSCLC and EGFR mutations. METHODS: A retrospective cohort analysis of patients with NSCLC screened for EGFR mutations (exons 18-21) between October 2009 and July 2013 was conducted...
October 24, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29078665/steps-in-the-development-of-a-vats-lobectomy-program
#20
Dario Amore, Carlo Curcio
Video-assisted thoracoscopic surgery (VATS) lobectomy has been employed in recent decades for the treatment of non-small cell lung cancer (NSCLC). Although trials have shown this procedure to be safe and feasible a VATS approach for lobectomy has not been widely used yet. Surgeons can go beyond this limit by following a specific operative plan focused on learning the minimally invasive technique in centers of excellence and then including: a pre-operative phase based on the radioclinical assessments and an operating phase designed to develop a methodical approach to VATS technique...
2017: J Vis Surg
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