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shirish gadgeel

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https://www.readbyqxmd.com/read/28164089/met-hgf-pathway-activation-as-a-paradigm-of-resistance-to-targeted-therapies
#1
REVIEW
Brian Ko, Tianfang He, Shirish Gadgeel, Balazs Halmos
Resistance to targeted therapeutics is a key issue limiting the long-term utility of these medications in the management of molecularly selected subsets of cancer patients, including patients with non-small cell lung cancer harboring oncogenic alterations affecting EGFR, ALK and other genes. Bypass resistance mediated by activation of MET kinase has emerged as a frequent, validated and pivotal resistance mechanism in multiple types of cancers. Biochemical understanding is accumulating to explain the unique role of MET in such bypass pathways, providing alternate downstream activation opportunities and intricate interactions during epithelial-mesenchymal transitions...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28073615/randomized-trial-of-a-question-prompt-list-to-increase-patient-active-participation-during-interactions-with-black-patients-and-their-oncologists
#2
Susan Eggly, Lauren M Hamel, Tanina S Foster, Terrance L Albrecht, Robert Chapman, Felicity W K Harper, Hayley Thompson, Jennifer J Griggs, Richard Gonzalez, Lisa Berry-Bobovski, Rifky Tkatch, Michael Simon, Anthony Shields, Shirish Gadgeel, Randa Loutfi, Haythem Ali, Ira Wollner, Louis A Penner
OBJECTIVE: Communication during racially-discordant interactions is often of poor quality and may contribute to racial treatment disparities. We evaluated an intervention designed to increase patient active participation and other communication-related outcomes during interactions between Black patients and non-Black oncologists. METHODS: Participants were 18 non-Black medical oncologists and 114 Black patients at two cancer hospitals in Detroit, Michigan, USA. Before a clinic visit to discuss treatment, patients were randomly assigned to usual care or to one of two question prompt list (QPL) formats: booklet (QPL-Only), or booklet and communication coach (QPL-plus-Coach)...
December 27, 2016: Patient Education and Counseling
https://www.readbyqxmd.com/read/28063799/phase-ii-trial-of-dose-dense-pemetrexed-gemcitabine-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer
#3
Bryan J Schneider, Gregory P Kalemkerian, Shirish M Gadgeel, Manuel Valdivieso, Deborah M Hackstock, Wei Chen, Lance K Heilbrun, John C Ruckdeschel, Antoinette J Wozniak
INTRODUCTION: Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC. METHODS: This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m(2)), gemcitabine (1200 mg/m(2)), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27979383/atezolizumab-versus-docetaxel-in-patients-with-previously-treated-non-small-cell-lung-cancer-oak-a-phase-3-open-label-multicentre-randomised-controlled-trial
#4
Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara
BACKGROUND: Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer. METHODS: We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1...
January 21, 2017: Lancet
https://www.readbyqxmd.com/read/27969533/ps01-66-biomarker-stratification-of-outcomes-of%C3%A2-third-generation-egfr-tki-therapy-in-patients-with-previously-treated-advanced-nsclc-topic-medical-oncology
#5
Heather Wakelee, Jonathan W Goldman, Shirish Gadgeel, David R Camidge, Karen L Reckamp, Sai-Hong I Ou, Helena A Yu, Benjamin Solomon, Stephen V Liu, Maurice Pérol, Nicholas F Dupuis, Alex Nickel, Chris Karlovich, Mitch Raponi, Sergey Yurasov, Jason Litten, Darrin Despain, Jean-Charles Soria, Lecia Sequist, David Carbone
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27913735/preoperative-pulmonary-rehabilitation-for-marginal-function-lung-cancer-patients
#6
Asra Hashmi, Frank A Baciewicz, Ayman O Soubani, Shirish M Gadgeel
Background This study aimed to evaluate the impact of preoperative pulmonary rehabilitation in lung cancer patients undergoing pulmonary resection surgery with marginal lung function. Methods Short-term outcomes of 42 patients with forced expiratory volume in 1 s < 1.6 L who underwent lung resection between 01/2006 and 12/2010 were reviewed retrospectively. They were divided into group A (no preoperative pulmonary rehabilitation) and group B (receiving pulmonary rehabilitation). In group B, a second set of pulmonary function tests was obtained...
January 2017: Asian Cardiovascular & Thoracic Annals
https://www.readbyqxmd.com/read/27863201/pooled-analysis-of-cns-response-to-alectinib-in-two-studies-of-pretreated-patients-with-alk-positive-non-small-cell-lung-cancer
#7
Shirish M Gadgeel, Alice T Shaw, Ramaswamy Govindan, Leena Gandhi, Mark A Socinski, D Ross Camidge, Luigi De Petris, Dong-Wan Kim, Alberto Chiappori, Denis L Moro-Sibilot, Michael Duruisseaux, Lucio Crino, Tommaso De Pas, Eric Dansin, Antje Tessmer, James Chih-Hsin Yang, Ji-Youn Han, Walter Bordogna, Sophie Golding, Ali Zeaiter, Sai-Hong Ignatius Ou
Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27822122/mesothelioma-in-the-united-states-a-surveillance-epidemiology-and-end-results-seer-medicare-investigation-of-treatment-patterns-and-overall-survival
#8
Jennifer L Beebe-Dimmer, Jon P Fryzek, Cecilia L Yee, Tapashi B Dalvi, David H Garabrant, Ann G Schwartz, Shirish Gadgeel
INTRODUCTION: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare database. MATERIALS AND METHODS: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27745820/carboplatin-and-pemetrexed-with-or-without-pembrolizumab-for-advanced-non-squamous-non-small-cell-lung-cancer-a-randomised-phase-2-cohort-of-the-open-label-keynote-021-study
#9
Corey J Langer, Shirish M Gadgeel, Hossein Borghaei, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Yang Ge, Harry Raftopoulos, Leena Gandhi
BACKGROUND: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC...
November 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27732997/predictive-and-prognostic-biomarkers-in-non-small-cell-lung-cancer
#10
Manish K Thakur, Shirish M Gadgeel
Therapy of non-small cell lung cancer (NSCLC) patients has evolved over the past few years with the incorporation of targeted therapy and immune therapy. These changes have increased the importance of prognostic and predictive biomarkers to enable practicing physicians in making the most appropriate treatment decisions for NSCLC patients. A variety of prognostic factors based on clinical and pathologic features determine the overall outcome of the patient and these factors do influence decisions regarding initiation of therapy...
October 2016: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27686971/phase-2-study-of-erlotinib-in-combination-with%C3%A2-linsitinib-osi-906-or-placebo-in-chemotherapy-naive-patients-with-non-small-cell-lung-cancer-and-activating-epidermal-growth-factor-receptor-mutations
#11
Natasha B Leighl, Naiyer A Rizvi, Lopes Gilberto de Lima, Wichit Arpornwirat, Charles M Rudin, Alberto A Chiappori, Myung-Ju Ahn, Laura Q M Chow, Lyudmila Bazhenova, Arunee Dechaphunkul, Patrapim Sunpaweravong, Keith Eaton, Jihong Chen, Sonja Medley, Srinivasu Poondru, Margaret Singh, Joyce Steinberg, Rosalyn A Juergens, Shirish M Gadgeel
INTRODUCTION: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes. PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non-small-cell lung cancer...
August 8, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27567356/outcomes-of-elderly-patients-who-receive-combined-modality-therapy-for-locally-advanced-non-small-cell-lung-cancer
#12
Mark Zaki, Michael Dominello, Gregory Dyson, Shirish Gadgeel, Antoinette Wozniak, Steven Miller, Peter Paximadis
BACKGROUND: The objective of this study was to review our institution's experience among patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with chemotherapy and radiation and to determine the prognostic significance of age. PATIENTS AND METHODS: Patients were included if they underwent sequential or concurrent chemoradiotherapy from 2006 to 2014 for LA-NSCLC. Patients were stratified according to age ≤70 and >70 years. Kaplan-Meier and Cox regression methods were performed to evaluate overall survival (OS) and progression-free survival (PFS)...
July 22, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27468937/a-highly-sensitive-and-quantitative-test-platform-for-detection-of-nsclc-egfr-mutations-in-urine-and-plasma
#13
Karen L Reckamp, Vladislava O Melnikova, Chris Karlovich, Lecia V Sequist, D Ross Camidge, Heather Wakelee, Maurice Perol, Geoffrey R Oxnard, Karena Kosco, Peter Croucher, Errin Samuelsz, Cecile Rose Vibat, Shiloh Guerrero, Jennifer Geis, David Berz, Elaina Mann, Shannon Matheny, Lindsey Rolfe, Mitch Raponi, Mark G Erlander, Shirish Gadgeel
INTRODUCTION: In approximately 60% of patients with NSCLC who are receiving EGFR tyrosine kinase inhibitors, resistance develops through the acquisition of EGFR T790M mutation. We aimed to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations from urine and plasma specimens is feasible. METHODS: Short footprint mutation enrichment next-generation sequencing assays were used to interrogate EGFR activating mutations and the T790M resistance mutation in urine or plasma specimens from patients enrolled in TIGER-X (NCT01526928), a phase 1/2 clinical study of rociletinib in previously treated patients with EGFR mutant-positive advanced NSCLC...
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27432227/molecular-mechanisms-of-resistance-to-first-and-second-generation-alk-inhibitors-in-alk-rearranged-lung-cancer
#14
Justin F Gainor, Leila Dardaei, Satoshi Yoda, Luc Friboulet, Ignaty Leshchiner, Ryohei Katayama, Ibiayi Dagogo-Jack, Shirish Gadgeel, Katherine Schultz, Manrose Singh, Emily Chin, Melissa Parks, Dana Lee, Richard H DiCecca, Elizabeth Lockerman, Tiffany Huynh, Jennifer Logan, Lauren L Ritterhouse, Long P Le, Ashok Muniappan, Subba Digumarthy, Colleen Channick, Colleen Keyes, Gad Getz, Dora Dias-Santagata, Rebecca S Heist, Jochen Lennerz, Lecia V Sequist, Cyril H Benes, A John Iafrate, Mari Mino-Kenudson, Jeffrey A Engelman, Alice T Shaw
: Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors...
October 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27383774/risk-of-lung-cancer-associated-with-copd-phenotype-based-on-quantitative-image-analysis
#15
Ann G Schwartz, Christine M Lusk, Angela S Wenzlaff, Donovan Watza, Stephanie Pandolfi, Laura Mantha, Michele L Cote, Ayman O Soubani, Garrett Walworth, Antoinette Wozniak, Christine Neslund-Dudas, Amy A Ardisana, Michael J Flynn, Thomas Song, David L Spizarny, Paul A Kvale, Robert A Chapman, Shirish M Gadgeel
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. This study evaluates alternative measures of COPD based on spirometry and quantitative image analysis to better define a phenotype that predicts lung cancer risk. METHODS: A total of 341 lung cancer cases and 752 volunteer controls, ages 21 to 89 years, participated in a structured interview, standardized CT scan, and spirometry. Logistic regression, adjusted for age, race, gender, pack-years, and inspiratory and expiratory total lung volume, was used to estimate the odds of lung cancer associated with FEV1/FVC, percent voxels less than -950 Hounsfield units on the inspiratory scan (HUI) and percent voxels less than -856 HU on expiratory scan (HUE)...
September 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27325865/the-effects-of-oncologist-implicit-racial-bias-in-racially-discordant-oncology-interactions
#16
Louis A Penner, John F Dovidio, Richard Gonzalez, Terrance L Albrecht, Robert Chapman, Tanina Foster, Felicity W K Harper, Nao Hagiwara, Lauren M Hamel, Anthony F Shields, Shirish Gadgeel, Michael S Simon, Jennifer J Griggs, Susan Eggly
PURPOSE: Health providers' implicit racial bias negatively affects communication and patient reactions to many medical interactions. However, its effects on racially discordant oncology interactions are largely unknown. Thus, we examined whether oncologist implicit racial bias has similar effects in oncology interactions. We further investigated whether oncologist implicit bias negatively affects patients' perceptions of recommended treatments (i.e., degree of confidence, expected difficulty)...
August 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27119128/lung-cancer-and-personalized-medicine-novel-therapies-and-clinical-management-preface
#17
EDITORIAL
Aamir Ahmad, Shirish M Gadgeel
No abstract text is available yet for this article.
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27062154/risk-of-brain-metastases-in-patients-with-nonmetastatic-lung-cancer-analysis-of-the-metropolitan-detroit-surveillance-epidemiology-and-end-results-seer-data
#18
Priscila H Goncalves, Stephanie L Peterson, Fawn D Vigneau, Ronald D Shore, William O Quarshie, Khairul Islam, Ann G Schwartz, Antoinette J Wozniak, Shirish M Gadgeel
BACKGROUND: Brain metastases (BM) remain an important cause of morbidity and mortality in patients with lung cancer. The current study evaluated population-based incidence and outcomes of BM in patients with nonmetastatic lung cancer. METHODS: Patients diagnosed with nonmetastatic first primary lung cancer between 1973 and 2011 in the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry were used for the current analysis. Age-adjusted odds ratios of developing BM based on various demographic characteristics and histology were calculated with 95% confidence intervals...
June 15, 2016: Cancer
https://www.readbyqxmd.com/read/26903362/plasma-biomarker-enrichment-of-clinical-prognostic-indices-in-malignant-pleural-mesothelioma
#19
Harvey I Pass, Chandra Goparaju, Osvaldo Espin-Garcia, Jessica Donington, Michele Carbone, Devalben Patel, Zhuo Chen, Ronald Feld, John Cho, Shirish Gadgeel, Antoinette Wozniak, Abraham Chachoua, Natasha Leighl, Ming-Sound Tsao, Marc de Perrot, Wei Xu, Geoffrey Liu
OBJECTIVES: Prognostic models for malignant pleural mesothelioma (MPM) are needed to prevent potentially futile outcomes. We combined MPM plasma biomarkers with validated clinical prognostic indices to determine whether stratification of risk for death in 194 patients with MPM improved. METHODS: Individuals were recruited from three different centers: a discovery cohort (83 patients with MPM) created by combining patients from two U.S. centers and a separate, independent cohort from Canada (111 patients with MPM)...
June 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/26831715/phase-i-dose-escalation-study-of-linsitinib-osi-906-and-erlotinib-in-patients-with-advanced-solid-tumors
#20
Valentine M Macaulay, Mark R Middleton, S Gail Eckhardt, Charles M Rudin, Rosalyn A Juergens, Richard Gedrich, Sven Gogov, Sean McCarthy, Srinivasu Poondru, Andrew W Stephens, Shirish M Gadgeel
PURPOSE: Cross-talk between type I IGF receptor (IGF1R), insulin receptor (INSR), and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of linsitinib, a potent oral IGF1R/INSR inhibitor, with EGFR inhibitor erlotinib. EXPERIMENTAL DESIGN: This open-label, dose-escalation study investigated linsitinib schedules S1: once daily intermittent (days 1-3 weekly); S2, once daily continuous; S3, twice-daily continuous; each with erlotinib 100-150 mg once daily; and a non-small cell lung cancer (NSCLC) expansion cohort...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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