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https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-pd-l-ligand-1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#1
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#2
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29146616/therapeutic-potential-of-afatinib-for-cancers-with-erbb2-her2-transmembrane-domain-mutations-g660d-and-v659e
#3
Hiromasa Yamamoto, Shinichi Toyooka, Takashi Ninomiya, Shigemi Matsumoto, Masashi Kanai, Shuta Tomida, Katsuyuki Kiura, Manabu Muto, Ken Suzawa, Patrice Desmeules, Mark G Kris, Bob T Li, Marc Ladanyi
We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2-mutant cancers. The familial lung cancer patient in one of the authors' institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29106880/utility-of-screening-questionnaire-and-polysomnography-to-predict-postoperative-outcomes-in-children
#4
Hiromi Kako, Jennifer Tripi, Hina Walia, Dmitry Tumin, Mark Splaingard, Kris R Jatana, Joseph D Tobias, Vidya T Raman
INTRODUCTION: The prevalence of pediatric obstructive sleep apnea (OSA) has increased concurrently with the increasing prevalence of obesity. We have previously validated a short questionnaire predicting the occurrence of OSA on polysomnography (PSG). This follow-up study assessed the utility of the questionnaire in predicting postoperative outcomes. METHODS: Children undergoing surgery and completing a sleep study were prospectively screened for OSA using a short questionnaire...
November 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/29089357/effects-of-co-occurring-genomic-alterations-on-outcomes-in-patients-with-kras-mutant-non-small-cell-lung-cancer
#5
Kathryn C Arbour, Emmett Jordan, Hyunjae Ryan Kim, Jordan Dienstag, Helena A Yu, Francisco Sanchez-Vega, Piro Lito, Michael Berger, David B Solit, Matthew Hellmann, Mark G Kris, Charles M Rudin, Ai Ni, Maria Arcila, Marc Ladanyi, Gregory J Riely
Purpose:KRAS mutations occur in approximately 25% of patients with non-small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS-mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS-mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy.Experimental Design: We identified patients with advanced KRAS-mutant NSCLC and evaluated the most common co-occurring genomic alterations...
October 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29028759/which-domains-of-the-odi-best-predict-change-in-physical-function-in-patients-after-surgery-for-degenerative-lumbar-spondylolisthesis
#6
Hamadi A Murphy, Eugene Warnick, Richard McGintee, Kristen Nicholson, Douglas A Hollern, Christie Stawicki, Daniel Tarazona, Gregory D Schroeder, Barrett I Woods, Mark F Kurd, Jeffrey A Rihn, Greg D Anderson, Christopher K Kepler, Alan S Hilibrand, Alexander R Vaccaro, Kris E Radcliff
STUDY DESIGN: Retrospective Review OBJECTIVE.: The purpose of this study is to determine the differential improvement of the various individual items of the ODI and to determine their relationship to other measures of HRQOL. SUMMARY OF BACKGROUND DATA: The oswestry disability index (ODI) is an easily scored, common, ten-item questionnaire about symptoms relevant to lumbar spine pathology. It is not clear if all of the items can be reliably applied to spine surgery...
October 12, 2017: Spine
https://www.readbyqxmd.com/read/28940498/twice-weekly-pulse-and-daily-continuous-dose-erlotinib-as-initial-treatment-for-patients-with-epidermal-growth-factor-receptor-mutant-lung-cancers-and-brain-metastases
#7
Kathryn C Arbour, Mark G Kris, Gregory J Riely, Ai Ni, Kathryn Beal, Mariza Daras, Sara A Hayes, Robert J Young, Christopher R Rodriguez, Linda Ahn, William Pao, Helena A Yu
BACKGROUND: In a phase 1 study of pulse/continuous-dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)-mutant lung cancers with untreated brain metastases. METHODS: Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly...
September 21, 2017: Cancer
https://www.readbyqxmd.com/read/28837374/antiemetics-american-society-of-clinical-oncology-clinical-practice-guideline-update-summary
#8
Paul J Hesketh, Kari Bohlke, Mark G Kris
No abstract text is available yet for this article.
August 24, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28759346/antiemetics-american-society-of-clinical-oncology-clinical-practice-guideline-update
#9
REVIEW
Paul J Hesketh, Mark G Kris, Ethan Basch, Kari Bohlke, Sally Y Barbour, Rebecca Anne Clark-Snow, Michael A Danso, Kristopher Dennis, L Lee Dupuis, Stacie B Dusetzina, Cathy Eng, Petra C Feyer, Karin Jordan, Kimberly Noonan, Dee Sparacio, Mark R Somerfield, Gary H Lyman
Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy...
October 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28743157/her2-mutations-in-lung-adenocarcinomas-a-report-from-the-lung-cancer-mutation-consortium
#10
Rathi N Pillai, Madhusmita Behera, Lynne D Berry, Mike R Rossi, Mark G Kris, Bruce E Johnson, Paul A Bunn, Suresh S Ramalingam, Fadlo R Khuri
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS: Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers...
November 1, 2017: Cancer
https://www.readbyqxmd.com/read/28714472/targeting-the-differential-addiction-to-anti-apoptotic-bcl-2-family-for-cancer-therapy
#11
Akane Inoue-Yamauchi, Paul S Jeng, Kwanghee Kim, Hui-Chen Chen, Song Han, Yogesh Tengarai Ganesan, Kota Ishizawa, Sylvia Jebiwott, Yiyu Dong, Maria C Pietanza, Matthew D Hellmann, Mark G Kris, James J Hsieh, Emily H Cheng
BCL-2 family proteins are central regulators of mitochondrial apoptosis and validated anti-cancer targets. Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differential addiction of cancer cells to anti-apoptotic BCL-2, BCL-XL or MCL-1, which correlated with the respective protein expression ratio. ABT-263 (navitoclax), a BCL-2/BCL-XL inhibitor, prevented BCL-XL from sequestering activator BH3-only molecules (BH3s) and BAX but not BAK. Consequently, ABT-263 failed to kill BCL-XL-addicted cells with low activator BH3s and BCL-XL overabundance conferred resistance to ABT-263...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28625636/prognostic-impact-of-ttf-1-expression-in-patients-with-stage-iv-lung-adenocarcinomas
#12
Juliana B Schilsky, Ai Ni, Linda Ahn, Sutirtha Datta, William D Travis, Mark G Kris, Jamie E Chaft, Natasha Rekhtman, Matthew D Hellmann
OBJECTIVES: Thyroid transcription factor 1 (TTF-1) is routinely tested in the diagnostic evaluation of suspected lung cancers, is commonly expressed by lung adenocarcinomas, and may modulate lung cancer biology. We examined the role of TTF-1 as a predictive and prognostic marker in patients with advanced lung adenocarcinomas. MATERIALS AND METHODS: We analyzed clinical, pathologic, and molecular features, treatments received, and overall survival obtained from the medical records of 479 consecutive patients at a single site with stage IV lung adenocarcinomas and evaluable TTF-1 expression...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28620111/dietary-fats-and-cardiovascular-disease-a-presidential-advisory-from-the-american-heart-association
#13
REVIEW
Frank M Sacks, Alice H Lichtenstein, Jason H Y Wu, Lawrence J Appel, Mark A Creager, Penny M Kris-Etherton, Michael Miller, Eric B Rimm, Lawrence L Rudel, Jennifer G Robinson, Neil J Stone, Linda V Van Horn
Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD...
July 18, 2017: Circulation
https://www.readbyqxmd.com/read/28586821/overall-survival-results-of-a-trial-assessing-patient-reported-outcomes-for-symptom-monitoring-during-routine-cancer-treatment
#14
COMPARATIVE STUDY
Ethan Basch, Allison M Deal, Amylou C Dueck, Howard I Scher, Mark G Kris, Clifford Hudis, Deborah Schrag
No abstract text is available yet for this article.
July 11, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28441082/adjuvant-systemic-therapy-and-adjuvant-radiation-therapy-for-stages-i-to-iiia-resectable-non-small-cell-lung-cancers-american-society-of-clinical-oncology-cancer-care-ontario-clinical-practice-guideline-update-summary
#15
Mark G Kris, Laurie E Gaspar, Jamie E Chaft, Erin B Kennedy
No abstract text is available yet for this article.
July 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28437162/adjuvant-systemic-therapy-and-adjuvant-radiation-therapy-for-stage-i-to-iiia-completely-resected-non-small-cell-lung-cancers-american-society-of-clinical-oncology-cancer-care-ontario-clinical-practice-guideline-update
#16
REVIEW
Mark G Kris, Laurie E Gaspar, Jamie E Chaft, Erin B Kennedy, Christopher G Azzoli, Peter M Ellis, Steven H Lin, Harvey I Pass, Rahul Seth, Frances A Shepherd, David R Spigel, John R Strawn, Yee C Ung, Michael Weyant
Purpose The panel updated the American Society of Clinical Oncology (ASCO) adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO convened an update panel and conducted a systematic review of the literature, investigating adjuvant therapy in resected non-small-cell lung cancers. Results The updated evidence base covered questions related to adjuvant systemic therapy and included a systematic review conducted by Cancer Care Ontario current to January 2016. A recent American Society for Radiation Oncology guideline and systematic review, previously endorsed by ASCO, was used as the basis for recommendations for adjuvant radiation therapy...
September 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28336552/prospective-comprehensive-molecular-characterization-of-lung-adenocarcinomas-for-efficient-patient-matching-to-approved-and-emerging-therapies
#17
Emmet J Jordan, Hyunjae R Kim, Maria E Arcila, David Barron, Debyani Chakravarty, JianJiong Gao, Matthew T Chang, Andy Ni, Ritika Kundra, Philip Jonsson, Gowtham Jayakumaran, Sizhi Paul Gao, Hannah C Johnsen, Aphrothiti J Hanrahan, Ahmet Zehir, Natasha Rekhtman, Michelle S Ginsberg, Bob T Li, Helena A Yu, Paul K Paik, Alexander Drilon, Matthew D Hellmann, Dalicia N Reales, Ryma Benayed, Valerie W Rusch, Mark G Kris, Jamie E Chaft, José Baselga, Barry S Taylor, Nikolaus Schultz, Charles M Rudin, David M Hyman, Michael F Berger, David B Solit, Marc Ladanyi, Gregory J Riely
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma, but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies...
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28147693/inverse-collimated-proton-radiography-for-imaging-thin-materials
#18
Matthew S Freeman, Jason Allison, Malcolm Andrews, Eric Ferm, John J Goett, Kris Kwiatkowski, Julian Lopez, Fesseha Mariam, Mark Marr-Lyon, Michael Martinez, Jason Medina, Patrick Medina, Frank E Merrill, Chris L Morris, Matthew M Murray, Paul Nedrow, Levi P Neukirch, Katherine Prestridge, Paolo Rigg, Alexander Saunders, Tamsen Schurman, Amy Tainter, Frans Trouw, Dale Tupa, Josh Tybo, Wendy Vogan-McNeil, Carl Wilde
Relativistic, magnetically focused proton radiography was invented at Los Alamos National Laboratory using the 800 MeV LANSCE beam and is inherently well-suited to imaging dense objects, at areal densities >20 g cm(-2). However, if the unscattered portion of the transmitted beam is removed at the Fourier plane through inverse-collimation, this system becomes highly sensitive to very thin media, of areal densities <100 mg cm(-2). Here, this inverse-collimation scheme is described in detail and demonstrated by imaging Xe gas with a shockwave generated by an aluminum plate compressing the gas at Mach 8...
January 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28002967/discovery-of-1s-2r-3s-4s-5r-6r-2-amino-3-3-4-difluorophenyl-sulfanylmethyl-4-hydroxy-bicyclo-3-1-0-hexane-2-6-dicarboxylic-acid-hydrochloride-ly3020371%C3%A2-hcl-a-potent-metabotropic-glutamate-2-3-receptor-antagonist-with-antidepressant-like-activity
#19
Mark D Chappell, Renhua Li, Stephon C Smith, Bruce A Dressman, Eric G Tromiczak, Allie E Tripp, Maria-Jesus Blanco, Tatiana Vetman, Steven J Quimby, James Matt, Thomas C Britton, Adam M Fivush, Jeffrey M Schkeryantz, Daniel Mayhugh, Jon A Erickson, Mark G Bures, Carlos Jaramillo, Mercedes Carpintero, José Eugenio de Diego, Mario Barberis, Susana Garcia-Cerrada, José F Soriano, Stephen Antonysamy, Shane Atwell, Iain MacEwan, Bradley Condon, Christine Sougias, Jing Wang, Aiping Zhang, Kris Conners, Chris Groshong, Stephen R Wasserman, John W Koss, Jeffrey M Witkin, Xia Li, Carl Overshiner, Keith A Wafford, Wesley Seidel, Xu-Shan Wang, Beverly A Heinz, Steven Swanson, John T Catlow, David W Bedwell, James A Monn, Charles H Mitch, Paul L Ornstein
As part of our ongoing efforts to identify novel ligands for the metabotropic glutamate 2 and 3 (mGlu2/3) receptors, we have incorporated substitution at the C3 and C4 positions of the (1S,2R,5R,6R)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid scaffold to generate mGlu2/3 antagonists. Exploration of this structure-activity relationship (SAR) led to the identification of (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride (LY3020371·HCl, 19f), a potent, selective, and maximally efficacious mGlu2/3 antagonist...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27987583/the-addition-of-anti-angiogenic-tyrosine-kinase-inhibitors-to-chemotherapy-for-patients-with-advanced-non-small-cell-lung-cancers-a-meta-analysis-of-randomized-trials
#20
Bob T Li, Tristan A Barnes, David L Chan, Jarushka Naidoo, Adrian Lee, Mustafa Khasraw, Gavin M Marx, Mark G Kris, Stephen J Clarke, Alexander Drilon, Charles M Rudin, Nick Pavlakis
OBJECTIVES: The role of anti-angiogenic tyrosine kinase inhibitors (AATKI) for patients with non-small-cell lung cancers (NSCLC) is uncertain. We conducted a comprehensive meta-analysis to assess the overall utility of adding AATKI to chemotherapy. MATERIALS AND METHODS: We included 15 randomized controlled trials (RCTs) of AATKI plus chemotherapy versus chemotherapy involving 7997 patients with advanced NSCLC. Meta-analysis was performed to obtain pooled hazard ratios (HR) for OS and PFS, and pooled odds ratios (OR) for objective response rate (ORR) and grade 3 or greater toxicity...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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