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https://www.readbyqxmd.com/read/29708428/interpathologist-diagnostic-agreement-for-non-small-cell-lung-carcinomas-using-current-and-recent-classifications
#1
William K Funkhouser, D Neil Hayes, Dominic T Moore, W Keith Funkhouser, Jason P Fine, HeeJoon Jo, Nana Nikolaishvilli-Feinberg, Mervi Eeva, Juneko E Grilley-Olson, Peter M Banks, Paolo Graziano, Elizabeth L Boswell, Goran Elmberger, Kirtee Raparia, Craig F Hart, Lynette M Sholl, Norris J Nolan, Karen J Fritchie, Ersie Pouagare, Timothy C Allen, Keith E Volmar, Paul W Biddinger, Daniel T Kleven, Michael J Papez, Deborah V Spencer, Natasha Rekhtman, Mari Mino-Kenudson, Lida Hariri, Brandon Driver, Philip T Cagle
CONTEXT: - Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications. OBJECTIVES: - To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure...
April 30, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29658848/neoadjuvant-pd-1-blockade-in-resectable-lung-cancer
#2
Patrick M Forde, Jamie E Chaft, Kellie N Smith, Valsamo Anagnostou, Tricia R Cottrell, Matthew D Hellmann, Marianna Zahurak, Stephen C Yang, David R Jones, Stephen Broderick, Richard J Battafarano, Moises J Velez, Natasha Rekhtman, Zachary Olah, Jarushka Naidoo, Kristen A Marrone, Franco Verde, Haidan Guo, Jiajia Zhang, Justina X Caushi, Hok Yee Chan, John-William Sidhom, Robert B Scharpf, James White, Edward Gabrielson, Hao Wang, Gary L Rosner, Valerie Rusch, Jedd D Wolchok, Taha Merghoub, Janis M Taube, Victor E Velculescu, Suzanne L Topalian, Julie R Brahmer, Drew M Pardoll
Background Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. Methods In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose...
April 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#3
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29656758/feasibility-of-endobronchial-ultrasound-transbronchial-needle-aspiration-for-massively-parallel-next-generation-sequencing-in-thoracic-cancer-patients
#4
Simon R Turner, Darren Buonocore, Patrice Desmeules, Natasha Rekhtman, Snjezana Dogan, Oscar Lin, Maria E Arcila, David R Jones, James Huang
INTRODUCTION: Next-generation sequencing (NGS) allows for the identification of a growing number of therapeutic and prognostic molecular targets. However, NGS typically requires greater quantities of DNA than traditional molecular testing does. Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure used to sample central thoracic lesions, but it is not well established whether this technique provides sufficient material for NGS. METHODS: We performed a retrospective review of EBUS-TBNA at our institution (3/1/14-9/28/16)...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29648885/commentary-on-testing-of-non-adenocarcinomas
#5
Natasha Rekhtman
No abstract text is available yet for this article.
April 12, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29610121/response-to-erbb3-directed-targeted-therapy-in-nrg1-rearranged-cancers
#6
Alexander Drilon, Romel Somwar, Biju P Mangatt, Henrik Edgren, Patrice Desmeules, Anja Ruusulehto, Roger S Smith, Lukas Delasos, Morana Vojnic, Andrew J Plodkowski, Joshua Sabari, Kenneth Ng, Joseph Montecalvo, Jason Chang, Huichun Tai, William W Lockwood, Victor Martinez, Gregory J Riely, Charles M Rudin, Mark G Kris, Maria E Arcila, Christopher Matheny, Ryma Benayed, Natasha Rekhtman, Marc Ladanyi, Gopinath Ganji
NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMAs) of the lung. The oncoprotein binds ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 monoclonal antibody therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase 1 trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four NRG1-rearranged IMA patients (including the index patient post-GSK2849330)...
April 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29605191/a-quality-improvement-intervention-to-reduce-emergency-department-radiography-for-bronchiolitis
#7
Joel Reiter, Adin Breuer, Oded Breuer, Saar Hashavya, David Rekhtman, Eitan Kerem, Malena Cohen-Cymberknoh
INTRODUCTION: Bronchiolitis is one of the most common infectious diseases in children and the most frequent cause of hospitalization in infants. Clinical practice guidelines recommend that a chest X-ray (CXR) should not be routinely obtained in the diagnosis of bronchiolitis, as studies have shown that they do not affect clinical outcomes, but rather lead to overuse of pharmacological agents and a longer length of hospital stay. OBJECTIVE: To determine whether active institution of bronchiolitis practice guidelines as part of a quality improvement project decreased the use of CXRs in the Pediatric Emergency Department (ED)...
April 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-1-pd-l1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#8
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)...
March 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29177675/clinical-evaluation-and-biomarker-profiling-of-hsp90-inhibitors
#9
Akira Yuno, Min-Jung Lee, Sunmin Lee, Yusuke Tomita, David Rekhtman, Brittni Moore, Jane B Trepel
Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have been in clinical development as anticancer agents since 1998. There have been 18 Hsp90 inhibitors (Hsp90i) that have entered the clinic, all of which, though structurally distinct, target the ATP-binding Bergerat fold of the chaperone N-terminus. Currently, there are five Hsp90 inhibitors in clinical trial and no approved drug in this class. One impediment to development of a clinically efficacious Hsp90 inhibitor has been the very low percentage of clinical trials that have codeveloped a predictive or pharmacodynamic marker of the anticancer activity inherent in this class of drugs...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29095036/novel-modification-of-histogel-based-cell-block-preparation-method-improved-sufficiency-for-molecular-studies
#10
Natasha Rekhtman, Darren J Buonocore, Dorota Rudomina, Maria Friedlander, Crisbane Dsouza, Gitika Aggarwal, Maria Arcila, Marcia Edelweiss, Oscar Lin
CONTEXT: - Cell block preparation methods vary substantially across institutions and are frequently suboptimal. The growing importance of biomarker testing in the era of targeted therapies makes optimization of cell block preparation critically important. OBJECTIVE: - To develop an improved cell block preparation method. DESIGN: - Ex vivo fine-needle aspirates and scrapes from surgically resected tumors were used to develop an improved HistoGel (Thermo Fisher Scientific, Waltham, Massachusetts)-based cell block preparation method...
November 2, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28884744/pulmonary-large-cell-neuroendocrine-carcinoma-with-adenocarcinoma-like-features-napsin-a-expression-and-genomic-alterations
#11
Natasha Rekhtman, Catherine M Pietanza, Joshua Sabari, Joseph Montecalvo, Hangjun Wang, Omar Habeeb, Kyuichi Kadota, Prasad Adusumilli, Charles M Rudin, Marc Ladanyi, William D Travis, Philippe Joubert
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like, and carcinoid-like. To further characterize adenocarcinoma-like subset, here we analyzed the expression of exocrine marker napsin A, along with TTF-1, in a large series of LCNECs (n=112), and performed detailed clinicopathologic and genomic analysis of napsin A-positive cases...
January 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28799111/erratum-to-micropapillary-and-or-solid-histologic-subtype-based-on-pre-treatment-biopsy-predicts-local-recurrence-after-thermal-ablation-of-lung-adenocarcinoma
#12
Song Gao, Seth Stein, Elena N Petre, Waleed Shady, Jeremy C Durack, Carole Ridge, Prasad S Adusumilli, Natasha Rekhtman, Stephen B Solomon, Etay Ziv
No abstract text is available yet for this article.
October 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28771603/expression-of-pd-l1-and-other-immunotherapeutic-targets-in-thymic-epithelial-tumors
#13
Kathryn C Arbour, Jarushka Naidoo, Keith E Steele, Ai Ni, Andre L Moreira, Natasha Rekhtman, Paul B Robbins, Joyson Karakunnel, Andreas Rimner, James Huang, Gregory J Riely, Matthew D Hellmann
INTRODUCTION: The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs...
2017: PloS One
https://www.readbyqxmd.com/read/28770314/micropapillary-and-or-solid-histologic-subtype-based-on-pre-treatment-biopsy-predicts-local-recurrence-after-thermal-ablation-of-lung-adenocarcinoma
#14
Song Gao, Seth Stein, Elena N Petre, Waleed Shady, Jeremy C Durack, Carole Ridge, Prasad S Adusumilli, Natasha Rekhtman, Stephen B Solomon, Etay Ziv
BACKGROUND: To investigate whether histologic subtyping from biopsies can predict local recurrence after thermal ablation for lung adenocarcinoma. METHODS: Patients treated with CT-guided thermal ablation for lung adenocarcinoma that had pre-ablation needle biopsy with analysis of histologic components were identified. Age, gender, smoking status, treatment indication (primary stage 1 tumor versus salvage), histologic subtype, ground-glass radiographic appearance, tumor size, ablation modality, and ablation margin were evaluated in relation to time to local recurrence (TTLR)...
February 2018: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28686497/immunohistochemistry-of-pulmonary-biomarkers-a-perspective-from-members-of-the-pulmonary-pathology-society
#15
Erik Thunnissen, Timothy Craig Allen, Julien Adam, Dara L Aisner, Mary Beth Beasley, Alain C Borczuk, Philip T Cagle, Vera Luiza Capelozzi, Wendy Cooper, Lida P Hariri, Izidor Kern, Sylvie Lantuejoul, Ross Miller, Mari Mino-Kenudson, Teodora Radonic, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Prudence Russell, Frank Schneider, Lynette M Sholl, Ming Sound Tsao, Marina Vivero, Yasushi Yatabe
The use of immunohistochemistry for the determination of pulmonary carcinoma biomarkers is a well-established and powerful technique. Immunohistochemisty is readily available in pathology laboratories, is relatively easy to perform and assess, can provide clinically meaningful results very quickly, and is relatively inexpensive. Pulmonary predictive biomarkers provide results essential for timely and accurate therapeutic decision making; for patients with metastatic non-small cell lung cancer, predictive immunohistochemistry includes ALK and programmed death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing...
March 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28639854/rapid-on-site-evaluation-of-endobronchial-ultrasound-guided-transbronchial-needle-aspirations-for-the-diagnosis-of-lung-cancer-a-perspective-from-members-of-the-pulmonary-pathology-society
#16
Deepali Jain, Timothy Craig Allen, Dara L Aisner, Mary Beth Beasley, Philip T Cagle, Vera Luiza Capelozzi, Lida P Hariri, Sylvie Lantuejoul, Ross Miller, Mari Mino-Kenudson, Sara E Monaco, Andre Moreira, Kirtee Raparia, Natasha Rekhtman, Anja Christiane Roden, Sinchita Roy-Chowdhuri, Gilda da Cunha Santos, Erik Thunnissen, Giancarlo Troncone, Marina Vivero
CONTEXT: - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. OBJECTIVE: - To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer...
February 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28625636/prognostic-impact-of-ttf-1-expression-in-patients-with-stage-iv-lung-adenocarcinomas
#17
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/28505004/a-subset-of-malignant-mesotheliomas-in-young-adults-are-associated-with-recurrent-ewsr1-fus-atf1-fusions
#18
Patrice Desmeules, Philippe Joubert, Lei Zhang, Hikmat A Al-Ahmadie, Christopher D Fletcher, Efsevia Vakiani, Deborah F Delair, Natasha Rekhtman, Marc Ladanyi, William D Travis, Cristina R Antonescu
Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28336552/prospective-comprehensive-molecular-characterization-of-lung-adenocarcinomas-for-efficient-patient-matching-to-approved-and-emerging-therapies
#19
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/28196596/chemosensitive-relapse-in-small-cell-lung-cancer-proceeds-through-an-ezh2-slfn11-axis
#20
Eric E Gardner, Benjamin H Lok, Valentina E Schneeberger, Patrice Desmeules, Linde A Miles, Paige K Arnold, Andy Ni, Inna Khodos, Elisa de Stanchina, Thuyen Nguyen, Julien Sage, John E Campbell, Scott Ribich, Natasha Rekhtman, Afshin Dowlati, Pierre P Massion, Charles M Rudin, John T Poirier
Small cell lung cancer is initially highly responsive to cisplatin and etoposide but in almost every case becomes rapidly chemoresistant, leading to death within 1 year. We modeled acquired chemoresistance in vivo using a series of patient-derived xenografts to generate paired chemosensitive and chemoresistant cancers. Multiple chemoresistant models demonstrated suppression of SLFN11, a factor implicated in DNA-damage repair deficiency. In vivo silencing of SLFN11 was associated with marked deposition of H3K27me3, a histone modification placed by EZH2, within the gene body of SLFN11, inducing local chromatin condensation and gene silencing...
February 13, 2017: Cancer Cell
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