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Tadeusz Robak, Krzysztof Warzocha, K Govind Babu, Yaroslav Kulyaba, Kazimierz Kuliczkowski, Kudrat Abdulkadyrov, Javier Loscertales, Iryna Kryachok, Janusz Kłoczko, Grygoriy Rekhtman, Wojciech Homenda, Jerzy Z Błoński, Astrid McKeown, Michele M Gorczyca, Jodi L Carey, Chai-Ni Chang, Steen Lisby, Ira V Gupta, Sebastian Grosicki
: In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18...
October 12, 2016: Leukemia & Lymphoma
Shaohua Lu, Kay See Tan, Kyuichi Kadota, Takashi Eguchi, Sarina Bains, Natasha Rekhtman, Prasad S Adusumilli, William D Travis
INTRODUCTION: Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma, however, it has not yet been characterized in squamous cell carcinoma (SCC). METHODS: We reviewed 445 resected stage I-III lung SCC and investigated the clinical significance of STAS. Cumulative incidence of recurrence (CIR) and lung cancer-specific death (CID) were evaluated by competing risks analyses and overall survival (OS) by Cox models. RESULTS: Of total 445 patients, 336 (76%) were >65 years old...
September 28, 2016: Journal of Thoracic Oncology
Jarushka Naidoo, Xuan Wang, Kaitlin M Woo, Tunc Iyriboz, Darragh Halpenny, Jane Cunningham, Jamie E Chaft, Neil H Segal, Margaret K Callahan, Alexander M Lesokhin, Jonathan Rosenberg, Martin Voss, Charles M Rudin, Hira Rizvi, Xue Hou, Katherine Rodriguez, Melanie Albano, Ruth-Ann Gordon, Charles Leduc, Natasha Rekhtman, Bianca Harris, Alexander M Menzies, Alexander D Guminski, Matteo S Carlino, Benjamin Y Kong, Jedd D Wolchok, Michael A Postow, Georgina V Long, Matthew D Hellmann
PURPOSE: Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. METHODS: Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015)...
September 19, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Shaozhou Ken Tian, J Keith Killian, Natasha Rekhtman, Ryma Benayed, Sumit Middha, Marc Ladanyi, Oscar Lin, Maria E Arcila
The value and suitability of cytology specimens for molecular diagnosis has been demonstrated by numerous studies. In practice, however, the success rates vary widely across institutions depending on the disease setting, institutional practices of acquisition, handling/processing, and testing methodologies. As the number of clinically relevant biomarkers continues to increase, more laboratories are turning to next-generation sequencing platforms for testing. Although amplicon-based next-generation sequencing assays, interrogating a limited genomic territory, can be performed with minimal input material, broader-based next-generation sequencing assays have higher DNA input requirements that may not be met if the small tissue samples are not acquired and handled appropriately...
September 2, 2016: Archives of Pathology & Laboratory Medicine
Maureen F Zakowski, Natasha Rekhtman, Manon Auger, Christine N Booth, Barbara Crothers, Mohiddean Ghofrani, Walid Khalbuss, Rodolfo Laucirica, Ann T Moriarty, Z Laura Tabatabai, Güliz A Barkan
CONTEXT: -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material...
October 2016: Archives of Pathology & Laboratory Medicine
Kirtee Raparia, Dara L Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain Borczuk, Philip T Cagle, Vera Capelozzi, Sanja Dacic, Lida P Hariri, Keith M Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Natasha Rekhtman, Anja C Roden, Sinchita Roy-Chowdhuri, Lynette Sholl, Maxwell L Smith, Eric Thunnissen, Ming Sound Tsao, Yasushi Yatabe
Transbronchial lung cryobiopsy involves using a cryoprobe rather than forceps to obtain a bronchoscopic biopsy. Recent studies have shown that transbronchial cryobiopsy provides a larger specimen than conventional transbronchial forceps biopsy, and that the interobserver agreement in the interpretation of cryobiopsy specimens is comparable to that of a surgical lung biopsy. This is encouraging, and transbronchial lung cryobiopsy clearly has a role in the workup and diagnosis of interstitial lung diseases. However, very few patients who have been studied underwent both transbronchial lung cryobiopsy and surgical lung biopsy, and the available data suggest that the diagnostic accuracy of cryobiopsy may not be similar to that of surgical lung biopsy...
July 21, 2016: Archives of Pathology & Laboratory Medicine
Benjamin H Lok, Eric E Gardner, Valentina E Schneeberger, Andy Ni, Patrice Desmeules, Natasha Rekhtman, Elisa de Stanchina, Beverly A Teicher, Nadeem Riaz, Simon N Powell, John T Poirier, Charles M Rudin
PURPOSE: PARP inhibitors (PARPi) are a novel class of small molecule therapeutics for small cell lung cancer (SCLC). Identification of predictors of response would advance our understanding, and guide clinical application, of this therapeutic strategy. EXPERIMENTAL DESIGN: Efficacy of PARP inhibitors olaparib, rucaparib, and veliparib, as well as etoposide and cisplatin in SCLC cell lines, and gene expression correlates, were analyzed using public datasets. HRD genomic scar scores were calculated from Affymetrix SNP 6...
July 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Luc Girard, Jaime Rodriguez-Canales, Carmen Behrens, Debrah M Thompson, Ihab W Botros, Hao Tang, Yang Xie, Natasha Rekhtman, William D Travis, Ignacio I Wistuba, John D Minna, Adi F Gazdar
PURPOSE: Most non-small cell lung cancers (NSCLCs) are now diagnosed from small specimens, and classification using standard pathology methods can be difficult. This is of clinical relevance as many therapy regimens and clinical trials are histology dependent. The purpose of this study was to develop an mRNA expression signature as an adjunct test for routine histo-pathological classification of NSCLCs. EXPERIMENTAL DESIGN: A microarray dataset of resected adenocarcinomas (ADC) and squamous cell carcinomas (SCC) was used as the learning set for an ADC-SCC signature...
June 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Lynette M Sholl, Dara L Aisner, Timothy Craig Allen, Mary Beth Beasley, Philip T Cagle, Vera L Capelozzi, Sanja Dacic, Lida P Hariri, Keith M Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Eric Thunnissen, Ming Tsao, Marina Vivero, Yasushi Yatabe
Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology...
August 2016: Archives of Pathology & Laboratory Medicine
Sinchita Roy-Chowdhuri, Dara L Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain Borczuk, Philip T Cagle, Vera Capelozzi, Sanja Dacic, Gilda da Cunha Santos, Lida P Hariri, Keith M Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Andre Moreira, Kirtee Raparia, Natasha Rekhtman, Lynette Sholl, Eric Thunnissen, Ming Sound Tsao, Marina Vivero, Yasushi Yatabe
The advent of targeted therapy in lung cancer has heralded a paradigm shift in the practice of cytopathology with the need for accurately subtyping lung carcinoma, as well as providing adequate material for molecular studies, to help guide clinical and therapeutic decisions. The variety and versatility of cytologic-specimen preparations offer significant advantages to molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is critical, not only from a lung cancer diagnosis standpoint but also for the myriad ancillary studies that are necessary to provide appropriate clinical management...
April 15, 2016: Archives of Pathology & Laboratory Medicine
A Drilon, I Bergagnini, L Delasos, J Sabari, K M Woo, A Plodkowski, L Wang, M D Hellmann, P Joubert, C S Sima, R Smith, R Somwar, N Rekhtman, M Ladanyi, G J Riely, M G Kris
BACKGROUND: RET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have shown durable clinical benefit with pemetrexed-based therapies in ALK- and ROS1-rearranged lung cancers, the benefits of pemetrexed-based treatments in patients with RET-rearranged lung cancers relative to other genomic subsets have not previously been explored. PATIENTS AND METHODS: A retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas and evidence of a RET, ROS1, or ALK rearrangement, or a KRAS mutation was conducted...
July 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Natasha Rekhtman, Maria C Pietanza, Matthew D Hellmann, Jarushka Naidoo, Arshi Arora, Helen Won, Darragh F Halpenny, Hangjun Wang, Shaozhou K Tian, Anya M Litvak, Paul K Paik, Alexander E Drilon, Nicholas Socci, John T Poirier, Ronglai Shen, Michael F Berger, Andre L Moreira, William D Travis, Charles M Rudin, Marc Ladanyi
PURPOSE: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm, whose biologic relationship to small cell lung carcinoma (SCLC) versus non-SCLC (NSCLC) remains unclear, contributing to uncertainty regarding optimal clinical management. To clarify these relationships, we analyzed genomic alterations in LCNEC compared with other major lung carcinoma types. EXPERIMENTAL DESIGN: LCNEC (n = 45) tumor/normal pairs underwent targeted next-generation sequencing of 241 cancer genes by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) platform and comprehensive histologic, immunohistochemical, and clinical analysis...
July 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jarushka Naidoo, Maria L Santos-Zabala, Tunc Iyriboz, Kaitlin M Woo, Camelia S Sima, John J Fiore, Mark G Kris, Gregory J Riely, Piro Lito, Afsheen Iqbal, Stephen Veach, Stephanie Smith-Marrone, Inderpal S Sarkaria, Lee M Krug, Charles M Rudin, William D Travis, Natasha Rekhtman, Maria C Pietanza
BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. MATERIALS AND METHODS: Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data...
January 21, 2016: Clinical Lung Cancer
Paul A Bunn, John D Minna, Alexander Augustyn, Adi F Gazdar, Youcef Ouadah, Mark A Krasnow, Anton Berns, Elisabeth Brambilla, Natasha Rekhtman, Pierre P Massion, Matthew Niederst, Martin Peifer, Jun Yokota, Ramaswamy Govindan, John T Poirier, Lauren A Byers, Murry W Wynes, David G McFadden, David MacPherson, Christine L Hann, Anna F Farago, Caroline Dive, Beverly A Teicher, Craig D Peacock, Jane E Johnson, Melanie H Cobb, Hans-Guido Wendel, David Spigel, Julien Sage, Ping Yang, M Catherine Pietanza, Lee M Krug, John Heymach, Peter Ujhazy, Caicun Zhou, Koichi Goto, Afshin Dowlati, Camilla Laulund Christensen, Keunchil Park, Lawrence H Einhorn, Martin J Edelman, Giuseppe Giaccone, David E Gerber, Ravi Salgia, Taofeek Owonikoko, Shakun Malik, Niki Karachaliou, David R Gandara, Ben J Slotman, Fiona Blackhall, Glenwood Goss, Roman Thomas, Charles M Rudin, Fred R Hirsch
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Natasha S Hochberg, Sergey Rekhtman, Julianne Burns, Lisa Ganley-Leal, Sina Helbig, Nathaniel S Watts, Gary H Brandeis, Jerrold J Ellner, C Robert Horsburgh
OBJECTIVES: In the USA, tuberculosis disease rates are highest in older adults. Diagnostic testing for latent tuberculosis infection (LTBI) has not been evaluated carefully in this group. The aim of this study was to define the relationship between tuberculin skin test (TST) results, T-SPOT.TB results, and T-cell responses to Mycobacterium tuberculosis antigens. METHODS: Long-term care facility residents with known prior TST results (positive or negative) were retested with TSTs and T-SPOT...
March 2016: International Journal of Infectious Diseases: IJID
Anders Österborg, Miklós Udvardy, Andrey Zaritskey, Per-Ola Andersson, Sebastian Grosicki, Grzegorz Mazur, Polina Kaplan, Michael Steurer, Anna Schuh, Marco Montillo, Iryna Kryachok, Jan Moritz Middeke, Yaroslav Kulyaba, Grygoriy Rekhtman, Michele Gorczyca, Siobhan Daly, Chai-Ni Chang, Steen Lisby, Ira Gupta
We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5...
September 2016: Leukemia & Lymphoma
Lynette M Sholl, Dara L Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain C Borczuk, Philip T Cagle, Vera Capelozzi, Sanja Dacic, Lida Hariri, Keith M Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Eric Thunnissen, Ming Sound Tsao, Yasushi Yatabe
The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell-mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non-small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors...
April 2016: Archives of Pathology & Laboratory Medicine
Eran Lavi, David Rekhtman, Yackov Berkun, Isaiah Wexler
UNLABELLED: The use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations...
March 2016: European Journal of Pediatrics
Danilo Maddalo, Eusebio Manchado, Carla P Concepcion, Ciro Bonetti, Joana A Vidigal, Yoon-Chi Han, Paul Ogrodowski, Alessandra Crippa, Natasha Rekhtman, Elisa de Stanchina, Scott W Lowe, Andrea Ventura
No abstract text is available yet for this article.
August 27, 2015: Nature
Paul K Paik, Alexander Drilon, Pang-Dian Fan, Helena Yu, Natasha Rekhtman, Michelle S Ginsberg, Laetitia Borsu, Nikolaus Schultz, Michael F Berger, Charles M Rudin, Marc Ladanyi
UNLABELLED: Mutations in the MET exon 14 RNA splice acceptor and donor sites, which lead to exon skipping, deletion of the juxtamembrane domain containing the CBL E3-ubiquitin ligase-binding site, and decreased turnover of the resultant aberrant MET protein, were previously reported to be oncogenic in preclinical models. We now report responses to the MET inhibitors crizotinib and cabozantinib in four patients with stage IV lung adenocarcinomas harboring mutations leading to MET exon 14 skipping, highlighting a new therapeutic strategy for the 4% of lung adenocarcinoma patients whose tumors harbor this previously underappreciated genetic alteration...
August 2015: Cancer Discovery
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