30 results on '"Arpita Desai"'
Search Results
2. Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer
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Tanya Jindal, Xiaolin Zhu, Rohit Bose, Vipul Kumar, Edward Maldonado, Prianka Deshmukh, Chase Shipp, Stephanie Feng, Michelle S. Johnson, Austin Angelidakis, Daniel Kwon, Hala T. Borno, Ivan de Kouchkovsky, Arpita Desai, Rahul Aggarwal, Lawrence Fong, Eric J. Small, Anthony Wong, Sima Porten, Jonathan Chou, Terence Friedlander, and Vadim S. Koshkin
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urothelial carcinoma ,antibody drug conjugate (ADC) ,enfortumab vedotin ,genetic markers ,next generating sequencing ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundEnfortumab vedotin (EV) is an antibody-drug conjugate approved for patients with treatment-refractory advanced urothelial carcinoma (aUC), however data on biomarkers of response is lacking.MethodsWe retrospectively identified all aUC patients at our institution who received EV monotherapy and had next-generation sequencing (NGS) data available. Patients were considered responders if they had a complete response or partial response on restaging scans during treatment. Observed response rate (ORR) was evaluated by local investigator and compared between responders and non-responders using Chi-squared test. A univariable analysis was conducted using the Cox proportional hazard test to assess for associations between baseline characteristics and most common somatic alterations (in ≥10% of patients) with patient survival outcomes [progression-free survival (PFS) and overall survival (OS)]. Somatic alterations were then individually evaluated in separate multivariate models while accounting for patient and clinical characteristics using Cox regression models.ResultsAmong 29 patients treated with EV monotherapy, 27 had available NGS data. Median age was 70, 24 (83%) were men, 19 (62%) were Caucasian, 15 (52%) had pure urothelial histology and 22 (76%) had primary tumor in the bladder. ORR was 41%, and PFS and OS for the overall cohort were 5.1 months and 10.2 months. Responders were enriched among patients with TP53, KDM6A and MDM2 alterations. Patients with these alterations, as well as those with composite TP53/MDM2 alterations (alterations in either TP53 or MDM2), also had increased ORR with EV treatment compared to patients without these alterations. In the univariable analysis, baseline albumin level ≥ 3.0g/dL and presence of composite TP53/MDM2 alterations were associated with a prolonged OS. Baseline ECOG 0/1, TP53 alterations and TP53/MDM2 alterations were associated with a prolonged PFS. In the multivariable analysis, TP53 and TP53/MDM2 alterations were genomic markers predictive of improved PFS after accounting for the relevant clinical characteristics.ConclusionIn this single-center retrospective analysis of aUC patients treated with EV, presence of TP53 or MDM2 somatic alterations, lower ECOG PS scores (ECOG 0 or 1) and higher albumin levels (≥3 g/dL) were associated with improved outcomes with EV treatment. Prospective and external validation of these findings in larger cohorts is warranted.
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- 2023
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3. APOBEC Mutational Signature and Tumor Mutational Burden as Predictors of Clinical Outcomes and Treatment Response in Patients With Advanced Urothelial Cancer
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Divya Natesan, Li Zhang, Henry J. Martell, Tanya Jindal, Patrick Devine, Bradley Stohr, Carlos Espinosa-Mendez, James Grenert, Jessica Van Ziffle, Nancy Joseph, Sarah Umetsu, Courtney Onodera, Michelle Turski, Emily Chan, Arpita Desai, Rahul Aggarwal, Anthony Wong, Sima Porten, Jonathan Chou, Terence Friedlander, Lawrence Fong, Eric J. Small, Alejandro Sweet-Cordero, and Vadim S. Koshkin
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bladder cancer ,APOBEC mutational signature ,tumor mutational burden ,next-generation sequencing ,urothelial cancer ,hypermutated ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionTumor mutational burden (TMB) and APOBEC mutational signatures are potential prognostic markers in patients with advanced urothelial carcinoma (aUC). Their utility in predicting outcomes to specific therapies in aUC warrants additional study.MethodsWe retrospectively reviewed consecutive UC cases assessed with UCSF500, an institutional assay that uses hybrid capture enrichment of target DNA to interrogate 479 common cancer genes. Hypermutated tumors (HM), defined as having TMB ≥10 mutations/Mb, were also assessed for APOBEC mutational signatures, while non-HM (NHM) tumors were not assessed due to low TMB. The logrank test was used to determine if there were differences in overall survival (OS) and progression-free survival (PFS) among patient groups of interest.ResultsAmong 75 aUC patients who had UCSF500 testing, 46 patients were evaluable for TMB, of which 19 patients (41%) had HM tumors and the rest had NHM tumors (27 patients). An additional 29 patients had unknown TMB status. Among 19 HM patients, all 16 patients who were evaluable for analysis had APOBEC signatures. HM patients (N=19) were compared with NHM patients (N=27) and had improved OS from diagnosis (125.3 months vs 35.7 months, p=0.06) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.04). Patients with APOBEC (N=16) were compared with remaining 56 patients, comprised of 27 NHM patients and 29 patients with unknown TMB, showing APOBEC patients to have improved OS from diagnosis (125.3 months vs 44.5 months, p=0.05) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.05). Neither APOBEC nor HM status were associated with response to immunotherapy.ConclusionsIn a large, single-institution aUC cohort assessed with UCSF500, an institutional NGS panel, HM tumors were common and all such tumors that were evaluated for mutational signature analysis had APOBEC signatures. APOBEC signatures and high TMB were prognostic of improved OS from diagnosis and both analyses also predicted inferior outcomes with chemotherapy treatment.
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- 2022
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4. TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor
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Li Zhang, Divya Natesan, Lawrence Fong, Emily Chan, David Y Oh, Son Ho, Ivan de Kouchkovsky, Errol J Philip, Francis Wright, Daniel M Kim, Daniel Kwon, Hansen Ho, Sima P Porten, Anthony C Wong, Arpita Desai, Franklin W Huang, Jonathan Chou, Raj S Pruthi, Eric J Small, Terence W Friedlander, and Vadim S Koshkin
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.Methods We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.Results We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).Conclusions The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.
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- 2021
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5. Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort
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Pedro Barata, Whitley Hatton, Arpita Desai, Vadim Koshkin, Ellen Jaeger, Charlotte Manogue, Patrick Cotogno, Malcolm Light, Brian Lewis, Jodi Layton, Oliver Sartor, Arnab Basu, Deepak Kilari, Hamid Emamekhoo, and Mehmet A. Bilen
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metastatic renal cell carcinoma ,immunotherapy ,PD-1/PD-L1 inhibitor ,monotherapy ,first-line treatment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: The treatment landscape of metastatic renal cell carcinoma has advanced significantly with the approval of combination regimens containing an immune checkpoint inhibitor (ICI) for patients with treatment-naïve disease. Little information is available regarding the activity of single-agent ICIs for patients with previously untreated mRCC not enrolled in clinical trials.Methods: This retrospective, multicenter cohort included consecutive treatment-naïve mRCC patients from six institutions in the United States who received ≥1 dose of an ICI outside a clinical trial, between June 2017 and October 2019. Descriptive statistics were used to analyze outcomes including objective best response rate (ORR), progression-free survival (PFS), and tolerability.Results: The final analysis included 27 patients, 70% men, median age 64 years (range 42–92), 67% Caucasian, and 33% with ECOG 2 or 3 at baseline. Most patients had intermediate risk (85%, IMDC) with clear cell (56%), papillary (26%), unclassified (11%), chromophobe (4%), and translocation (4%) RCC. All patients had evidence of metastatic disease involving the lungs (59%), lymph node (41%), CNS (19%), liver (11%), adrenal gland (11%), and bone (11%). The median time on ICI was 3.1 (0.1–26.8) months, and the median PFS was 6.3 (95% CI, 0–18.6) months. Among the 21 patients with an evaluable response, the best ORR was 33%, including two complete responses and five partial responses. The ORR was 29% (n = 1 complete response, n = 5 partial response) in clear cell and 5% (n = 1 complete response) in non-clear cell RCC. Adverse events (AEs) of any cause were reported in 37% and included fatigue (11%), dermatitis (11%), diarrhea (7%), and shortness of breath (7%). Significant AEs (30%) included shortness of breath (7%), acute kidney injury (4%), dermatitis (4%), Clostridium difficile infection (4%), cerebrovascular accident (4%), and fatigue (7%). Three patients discontinued therapy due to grade 4 AEs.Conclusions: In this multi-institutional case series, single-agent ICI demonstrated objective responses and was well tolerated in a heterogeneous treatment-naïve mRCC cohort. ICI monotherapy is not the standard of care for patients with mRCC, and further investigation is necessary to explore predictive biomarkers for optimal treatment selection in this setting.
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- 2020
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6. Alterations in genes other than EGFR/ALK/ROS1 in non-small cell lung cancer: trials and treatment options
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Arpita Desai, Smitha P. Menon, and Grace K. Dy
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RAS ,RAF ,MEK ,receptor tyrosine kinases (RTK) ,fibroblast growth factor receptor (FGFR) ,non-small cell lung cance (NSCLC) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.
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- 2016
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7. Impact of squamous differentiation on clinical outcomes and molecular profiling in metastatic urothelial carcinoma (mUC) patients (pts) treated with immune checkpoint inhibitors (ICIs) or enfortumab vedotin (EV)
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Tanya Jindal, Li Zhang, Prianka Deshmukh, Kevin Reyes, Emily Chan, Vipul Kumar, Xiaolin Zhu, Edward Maldonado, Stephanie Feng, Michelle Johnson, Austin Angelidakis, Daniel Kwon, Arpita Desai, Hala T Borno, Rohit Bose, Anthony Wong, Julian Hong, Peter Carroll, Maxwell Meng, Sima Porten, Rahul Aggarwal, Eric J Small, Lawrence Fong, Jonathan Chou, Terence Friedlander, Ivan de Kouchkovsky, and Vadim S Koshkin
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Oncology ,Urology - Published
- 2023
8. Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology
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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Ajjai Alva, Michael Baine, Kathryn Beckermann, Maria I. Carlo, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Arpita Desai, Yasser Ged, Saby George, John L. Gore, Naomi Haas, Steven L. Hancock, Payal Kapur, Christos Kyriakopoulos, Elaine T. Lam, Primo N. Lara, Clayton Lau, Bryan Lewis, David C. Madoff, Brandon Manley, M. Dror Michaelson, Amir Mortazavi, Lakshminarayanan Nandagopal, Elizabeth R. Plimack, Lee Ponsky, Sundhar Ramalingam, Brian Shuch, Zachary L. Smith, Jeffrey Sosman, Mary A. Dwyer, Lisa A. Gurski, and Angela Motter
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Oncology ,Humans ,Medical Oncology ,Carcinoma, Renal Cell ,Kidney Neoplasms ,Article - Abstract
The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as “Preferred,” “Other Recommended Regimens,” or “Useful in Certain Circumstances.” This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.
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- 2022
9. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
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Thomas Powles, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Thomas Ferguson, Stefan N Symeonides, Jaroslav Hajek, Howard Gurney, Yen-Hwa Chang, Jae Lyun Lee, Naveed Sarwar, Antoine Thiery-Vuillemin, Marine Gross-Goupil, Mauricio Mahave, Naomi B Haas, Piotr Sawrycki, Joseph E Burgents, Lei Xu, Kentaro Imai, David I Quinn, Toni K Choueiri, Toni Choueiri, Thomas R. Ferguson, Tzu-Ping Lin, Stefan N. Symeonides, Naomi B. Haas, Howard P. Gurney, Christine Chevreau, John M. Burke, Gurjyot Doshi, Bohuslav Melichar, Delphine Topart, Stephane Oudard, Evgeniy Kopyltsov, Hans-Joerg Hammers, David I. Quinn, Ajjai Alva, Juliana de Janoski Menezes, Adriano Goncalves e Silva, Eric W. Winquist, Alketa Hamzaj, Giuseppe Procopio, Boguslawa Karaszewska, Ewa M. Nowakowska-Zajdel, Boris Y. Alekseev, Rustem A. Gafanov, Adel Izmailov, Andrey Semenov, Sergey G. Afanasyev, Oleg N. Lipatov, Thomas B. Powles, Sandy Srinivas, David McDermott, Samith T. Kochuparambil, Ian D. Davis, Katriina Peltola, Roberto Sabbatini, Jinsoo Chung, Michail I. Shkolnik, Vsevolod B. Matveev, Pablo Gajate Borau, Steven McCune, Thomas E. Hutson, Alejandro Dri, Silvio Correia Sales, Carrie Yeung, Carmen Marcela Alcala Castro, Peter Bostrom, Brigitte Laguerre, Consuelo Buttigliero, Ugo de Giorgi, Eugeniy A. Fomin, Yousef Zakharia, Clara Hwang, Eric A. Singer, Jeffrey T. Yorio, David Waterhouse, Ruben Dario Kowalyszyn, Margarita Sonia Alfie, Eduardo Yanez Ruiz, Tomas Buchler, Krista Kankaanranta, Gianluigi Ferretti, Go Kimura, Kazuo Nishimura, Naoya Masumori, Satoshi Tamada, Haruaki Kato, Hiroshi Kitamura, Iwona Danielewicz, Joanna Wojcik-Tomaszewska, Nuria Sala Gonzalez, Kun-Yuan Chiu, Michael B. Atkins, Elisabeth Heath, Gustavo Adolfo Rojas-Uribe, Manuel Enrique Gonzalez Fernandez, Susan Feyerabend, Sandro Pignata, Kazuyuki Numakura, Bozena Cybulska Stopa, Ruslan Zukov, Miguel Angel Climent Duran, Pablo Jose Maroto Rey, Alvaro Montesa Pino, Chao-Hsiang Chang, Salil Vengalil, Tom S. Waddell, Patrick W. Cobb, Ralph Hauke, Daniel M. Anderson, John Sarantopoulos, Theodore Gourdin, Tian Zhang, Gautam Jayram, Luis Enrique Fein, Carole Harris, Patricia Medeiros Milhomem Beato, Francisco Flores, Angela Estay, Juan Andres Rubiano, Jens Bedke, Stefan Hauser, Andreas Neisius, Jonas Busch, Satoshi Anai, Hiroyuki Tsunemori, Dariusz Sawka, Bozena Sikora-Kupis, Jose Angel Arranz, Ignacio Delgado, Chung-Hsin Chen, Elizabeth Gunderson, Scott Tykodi, Alan Koletsky, Kevin Chen, Manish Agrawal, Diego Lucas Kaen, Juan Pablo Sade, Marcelo Daniel Tatangelo, Francis Parnis, Fernando Maciel Barbosa, Genevieve Faucher, Nayyer Iqbal, Daniele Marceau, Jean-Benoit Paradis, Nawar Hanna, Alejandro Acevedo, Carolina Ibanez, Luis Villanueva, Pedro Pablo Galaz, Isabel Cristina Durango, Ray Manneh, Zdenek - Kral, Petra Holeckova, Heikki Hakkarainen, Hanna Ronkainen, Sophie Abadie-Lacourtoisie, Sophie Tartas, Peter J. Goebell, Marc-Oliver Grimm, Thomas Hoefner, Manfred Wirth, Andrej Panic, Wolfgang Schultze-Seemann, Akira Yokomizo, Ryuichi Mizuno, Hirotsugu Uemura, Masatoshi Eto, Masao Tsujihata, Yoshihisa Matsukawa, Yoji Murakami, Miso Kim, Paul Hamberg, Malgorzata Marczewska-Skrodzka, Cezary Szczylik, Alison C. Humphreys, Peter Jiang, Birendra Kumar, Gary Lu, Arpita Desai, Jose Antonio Karam, George Keogh, Mark Fleming, Juan Jose Zarba, Viviana E. Leiva, Guillermo Ariel Mendez, Samuel J. Harris, Stephen J. Brown, Joao Neif Antonio Junior, Rita de Cassia Costamilan, Roberto Odebrecht Rocha, David Muniz, Leandro Brust, Aly-Khan Lalani, Jeffrey Graham, Michael Levesque, Francisco Orlandi, Rostislav Kotasek, Jean L. Deville, Delphine Borchiellini, Axel Merseburger, Michael Rink, Frederik Roos, Ray McDermott, Masafumi Oyama, Yoshiaki Yamamoto, Yoshihiko Tomita, Yuji Miura, Naomasa Ioritani, Hans Westgeest, Tomasz Kubiatowski, Wieslaw Bal, Regina Girones Sarrio, Julie Rowe, Debra M. Prow, Francis Senecal, Neda Hashemi-Sadraei, Scott W. Cole, Stephan D. Kendall, Donald A. Richards, Ian D. Schnadig, and Mukul Gupta
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Adult ,Oncology ,Double-Blind Method ,Antineoplastic Combined Chemotherapy Protocols ,Hypertension ,Humans ,Antibodies, Monoclonal, Humanized ,Carcinoma, Renal Cell ,Nephrectomy ,Kidney Neoplasms ,Follow-Up Studies - Abstract
Background: The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. Methods: In the multicentre, randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial, adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence were enrolled at 213 hospitals and cancer centres in North America, South America, Europe, Asia, and Australia. Eligible participants had an Eastern Cooperative Oncology Group performance status of 0 or 1, had undergone nephrectomy 12 weeks or less before randomisation, and had not received previous systemic therapy for advanced renal cell carcinoma. Participants were randomly assigned (1:1) via central permuted block randomisation (block size of four) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. Randomisation was stratified by metastatic disease status (M0 vs M1), and the M0 group was further stratified by ECOG performance status and geographical region. All participants and investigators involved in study treatment administration were masked to the treatment group assignment. The primary endpoint was disease-free survival by investigator assessment in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was assessed in the safety population, comprising all participants who received at least one dose of pembrolizumab or placebo. As the primary endpoint was met at the first interim analysis, updated data are reported without p values. This study is ongoing, but no longer recruiting, and is registered with ClinicalTrials.gov, NCT03142334. Findings: Between June 30, 2017, and Sept 20, 2019, 994 participants were assigned to receive pembrolizumab (n=496) or placebo (n=498). Median follow-up, defined as the time from randomisation to data cutoff (June 14, 2021), was 30·1 months (IQR 25·7–36·7). Disease-free survival was better with pembrolizumab compared with placebo (HR 0·63 [95% CI 0·50–0·80]). Median disease-free survival was not reached in either group. The most common all-cause grade 3–4 adverse events were hypertension (in 14 [3%] of 496 participants) and increased alanine aminotransferase (in 11 [2%]) in the pembrolizumab group, and hypertension (in 13 [3%] of 498 participants) in the placebo group. Serious adverse events attributed to study treatment occurred in 59 (12%) participants in the pembrolizumab group and one (
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- 2022
10. Serial stereotactic body radiation therapy for oligometastatic prostate cancer detected by novel PET-based radiotracers
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Daniel H. Kwon, Nonna Shakhnazaryan, David Shui, Julian C. Hong, Osama Mohamad, Ivan de Kouchkovsky, Hala T. Borno, Rohit Bose, Jonathan Chou, Arpita Desai, Lawrence Fong, Terence W. Friedlander, Vadim S. Koshkin, Rahul R. Aggarwal, Felix Y. Feng, Thomas A. Hope, and Eric J. Small
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Oncology ,Urology - Abstract
Radiopharmaceuticals, including Ga-68-prostate specific membrane antigen (PSMA)-11 and F-18-Fluciclovine, are increasingly used to inform therapies for prostate cancer (CaP). Stereotactic body radiation therapy (SBRT) to PET-detected oligometastatic CaP has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT) compared to observation. For men who subsequently develop oligorecurrent CaP, outcomes following second SBRT are unknown.A retrospective cohort study was conducted. Eligibility criteria included patients with oligometastatic (1-5 lesions) CaP detected on PSMA or Fluciclovine PET who underwent 2 consecutive SBRT courses to tracer-avid sites. Data on stage, tracer type, concurrent systemic therapy, and prostate-specific antigen (PSA) responses for first SBRT (SBRT1) and second SBRT (SBRT2) were collected. Outcomes included PSA decline ≥50% (PSA50), PFS after SBRT2, and ADT initiation or intensification-free survival after SBRT2. Factors potentially associated with PSA50 after SBRT2 was evaluated with multivariable logistic regression. Factors potentially associated with PFS and ADT initiation/intensification-free survival after SBRT2 were evaluated with separate multivariable Cox proportional-hazards models.Twenty-five patients were identified. At SBRT2, oligorecurrence was detected on PSMA and Fluciclovine PET in 17 (68%) and 8 (32%) patients, respectively. Fifteen (60%) patients had castration-sensitive disease and 10 (40%) had castration-resistant disease. After SBRT2, 16 (64%) achieved a PSA50 response, median PFS was 11.0mo, and median ADT initiation/intensification-free survival was 23.2mo. On multivariable analysis, maximum percent change in PSA after SBRT1 (OR 0.94, 95%CI 0.88-0.99, P = 0.046) and concurrent change in systemic therapy (OR 21.61, 95%CI 1.12-417.9, P = 0.042) were associated with PSA50 responses after SBRT2. PSA50 response after SBRT1 was associated with improved PFS (HR 0.36, 95%CI 0.00-0.42, P = 0.008) and ADT initiation/intensification-free survival (HR 0.07, 95%CI 0.01-0.68, P = 0.021) after SBRT2. From SBRT1 to last follow-up (median 48 months), 7 (28%) patients remained ADT-free.Serial SBRT for oligometastatic CaP detected on PSMA or Fluciclovine PET is feasible and can achieve PSA declines, with or without systemic therapy. Degree of biochemical response to first SBRT warrants further study as a potential predictor of PSA response, PFS, and ADT initiation/intensification-free survival following a subsequent SBRT course. This preliminary evidence provides rationale for larger, prospective studies of this strategy.
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- 2023
11. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021
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Brittany McCreery, Bryan Lewis, Naomi B. Haas, Lakshminarayanan Nandagopal, Mary A. Dwyer, Angela D. Motter, Christos Kyriakopoulos, Ajjai Alva, Maria I. Carlo, Phillip M. Pierorazio, M. Dror Michaelson, Sundhar Ramalingam, Brandon Manley, Clayton Lau, Lee Ponsky, Eric Jonasch, Neeraj Agarwal, David C. Madoff, Elizabeth R. Plimack, Bradley G. Somer, Jeffrey A. Sosman, Robert J. Motzer, Amir Mortazavi, Steven L. Hancock, Shawna L. Boyle, Elaine T. Lam, Ithaar Derweesh, Brian Shuch, Katy Beckermann, Arpita Desai, Saby George, Brian A. Costello, Zachary L. Smith, John L. Gore, and Toni K. Choueiri
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,MEDLINE ,Treatment options ,urologic and male genital diseases ,medicine.disease ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Carcinoma ,Medicine ,030212 general & internal medicine ,business ,Intensive care medicine ,Stage iv ,Kidney cancer ,Genetic testing - Abstract
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.
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- 2020
12. Synthesis of Calix-Salen Silver Corates for Evaluation of Their Antimicrobial and Anticancer Activities
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Arpita Desai, Hetal Roy, and Mihamee Deolalkar
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Engineering ,Thesaurus (information retrieval) ,business.industry ,medicine.drug_class ,General Chemical Engineering ,Antibiotics ,General Chemistry ,Antimicrobial ,Article ,World Wide Web ,Chemistry ,medicine ,business ,QD1-999 - Abstract
Silver-based products are becoming popular as antimicrobial agents because of the failure of antibiotics available for tackling the drug-resistant microbial strains. As silver is well tolerated by normal human cells, silver complexes have emerged as important antineoplastic agents. Further, if silver ions are encapsulated within an organic molecule—an azacorand—it may serve as a better substitute for cisplatin or other metal complexes. The calix-salen-type corates were synthesized using silver ions as the template. 5,5′-methylene-bis-salicylaldehyde was reacted with ethylene diamine in methanol at room temperature in the presence of silver nitrate. The resultant corand trapped the silver template in their cavity. The electron-withdrawing and electron-releasing groups like −NO2, −Br, −C(CH3)3, and −OCH3 were substituted on the bis-aldehyde to study their effects on the antimicrobial and anticancer activities of silver corates. The silver corates were found to have better antimicrobial activity than some of the standard drugs. Bromo-substituted corate-3, nitro-substituted corate-4, and tert-butyl-substituted corate-5 were found to be potent antibacterial agents among all. The bromo-substituted corate-3 was found to be the most potent fungicidal agent among all silver corates. The result of antineoplastic activity suggests that unsubstituted corate-1 and bromo-substituted corate-3 are potential candidates to be used as therapeutic molecules for cancer treatment, which requires further validation.
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- 2019
13. Mobile Audio Recording Technology to Promote Informed Decision Making in Advanced Prostate Cancer
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Daniel H. Kwon, Sneha Karthikeyan, Alison Chang, Hala T. Borno, Vadim S. Koshkin, Arpita Desai, Rohit Bose, Terence Friedlander, Tammy Rodvelt, Patricia Li, Eric J. Small, Rahul R. Aggarwal, and Jeffrey Belkora
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Male ,Prostatic Neoplasms, Castration-Resistant ,Technology ,Oncology ,Oncology (nursing) ,Health Policy ,Decision Making ,Humans ,Pilot Projects ,Referral and Consultation - Abstract
PURPOSE: Men with metastatic castration-resistant prostate cancer increasingly encounter complex treatment decisions. Consultation audio recordings and summaries promote patient informed decision making but are underutilized. Mobile recording software applications may increase access. Little is known regarding the feasibility of implementation in clinical encounters. METHODS: We conducted a mixed-methods pilot study in men with progressive metastatic castration-resistant prostate cancer. We instructed patients to use a mobile software application to record an oncology visit. Patients could share the recording with our patient scribing program to receive a written summary. We assessed feasibility and acceptability with postvisit surveys. We measured patient-reported helpfulness of the intervention in decision making and change in Decisional Conflict Scale–informed subscale. We conducted semistructured interviews to explore implementation and analyzed transcripts using thematic analysis. RESULTS: Across 20 patients, 18 (90%) recorded their visits. Thirteen of 18 (72%) listened to the recording, and 14 of 18 (78%) received a summary. Eighteen of 20 (90%) visits were telehealth. Fourteen patients (70% of all 20; 78% of 18 question respondents) found the application easy to use. Nine patients (50% of 18 recording patients; 90% of 10 question respondents) reported that the recording helped treatment decision making. Decisional conflict decreased from baseline to 1-week postvisit (47.4-28.5, P < .001). Interviews revealed benefits, facilitators, contextual factors, and technology and patient-related barriers to recordings and summaries. CONCLUSION: In this single-institution academic setting, a mobile application for patients to record consultations was a feasible, acceptable, and potentially valued intervention that improved decision making in the telehealth setting. Studies in larger, diverse populations are needed.
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- 2021
14. Micellization and clouding behaviour of an ionic surfactant in a deep eutectic solvent: A case of the reline-water mixture
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Darshna Hirpara, Brijesh Patel, Vishwajit Chavda, Arpita Desai, and Sanjeev Kumar
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Materials Chemistry ,Physical and Theoretical Chemistry ,Condensed Matter Physics ,Spectroscopy ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2022
15. Multi-institutional Analysis of the Clinical and Genomic Characteristics of Black Patients with Metastatic Hormone-Sensitive Prostate Cancer
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Meredith N Freeman, Albert Jang, Jason Zhu, Farhad Sanati, Lakshminarayanan Nandagopal, Deepak Ravindranathan, Arpita Desai, Audrey Phone, Roberto Nussenzveig, Ellen Jaeger, Sydney A Caputo, Vadim S Koshkin, Umang Swami, Arnab Basu, Mehmet A Bilen, Neeraj Agarwal, Oliver Sartor, Earle F Burgess, and Pedro C Barata
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Male ,Cancer Research ,Prostatic Neoplasms, Castration-Resistant ,Treatment Outcome ,Oncology ,Humans ,Prostatic Neoplasms ,Androgen Antagonists ,Middle Aged ,Hormones ,Retrospective Studies - Abstract
Background The outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) have significantly improved through treatment intensification, yet Black representation in those studies is suboptimal. Methods A multi-institutional, retrospective analysis of Black men with mHSPC was conducted, focusing on baseline demographics, treatment patterns, genomic profiles, clinical outcomes including prostate-specific antigen response, time to castrate-resistant prostate cancer (CRPC), and subsequent treatments. Results A total of 107 patients, median age 64 years, 62% with de novo metastases at diagnosis and 64% with high-volume disease, were included. Twenty-nine patients (27%) were treated with androgen deprivation therapy (ADT) with and without first generation anti-androgens, while 20%, 38% and 5% received chemotherapy, abiraterone, and enzalutamide, respectively. At time of data cut-off, 57 (54%) patients had developed CRPC, with a median time to CRPC of 25.4 months (95% CI 20.3-30.4). The median time to CRPC was 46.3 months (18.9-73.7) and 23.4 months (18.6-28.2) for patients who received ADT with or without first-generation anti-androgens and treatment intensification, respectively. The 2-year survival rate was 93.3%, and estimated median overall survival of was 74.9 months (95% CI, 68.7-81.0). Most patients (90%) underwent germline testing; the most frequent known alterations were found within the DNA repair group of genes. Somatic testing revealed pathogenic alterations of interest, notably TP53 (24%) and CDK12 (12%). Conclusion In our cohort, Black men with mHSPC presented with a high proportion of de novo metastases and high-volume disease. Treatment outcomes were very favorable with ADT-based regimens. The genomic landscape suggests different molecular profile relative to White patients with potential therapeutic implications.
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- 2021
16. TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor
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Vadim S. Koshkin, Sima P. Porten, Anthony C. Wong, David Y. Oh, Lawrence Fong, Arpita Desai, Ivan de Kouchkovsky, Eric J. Small, Francis Wright, Hansen Ho, Daniel Kwon, Errol J. Philip, Raj S. Pruthi, Divya Natesan, Terence W. Friedlander, Son Ho, Li Zhang, Jonathan Chou, Emily Chan, Franklin W. Huang, and Daniel M Kim
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Time Factors ,medicine.medical_treatment ,DNA Mutational Analysis ,Logistic regression ,0302 clinical medicine ,Risk Factors ,Immunology and Allergy ,Telomerase ,Immune Checkpoint Inhibitors ,RC254-282 ,Cancer ,screening and diagnosis ,Tumor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,High-Throughput Nucleotide Sequencing ,Progression-Free Survival ,Detection ,030220 oncology & carcinogenesis ,Cohort ,Molecular Medicine ,Female ,immunotherapy ,urinary bladder neoplasms ,4.2 Evaluation of markers and technologies ,medicine.medical_specialty ,Urologic Neoplasms ,Metastatic Urothelial Carcinoma ,Immunology ,Risk Assessment ,Promoter Regions ,03 medical and health sciences ,Genetic ,Predictive Value of Tests ,Clinical Research ,Internal medicine ,medicine ,Genetics ,Humans ,Retrospective Studies ,Aged ,Pharmacology ,Chemotherapy ,Performance status ,Proportional hazards model ,business.industry ,Carcinoma ,Human Genome ,Immunotherapy ,030104 developmental biology ,Good Health and Well Being ,Genetic marker ,tumor biomarkers ,Mutation ,genetic markers ,Urothelium ,business ,Biomarkers - Abstract
BackgroundImmune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.MethodsWe undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.ResultsWe identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).ConclusionsThe presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.
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- 2021
17. Treatment of advanced renal cell carcinoma patients with cabozantinib, an oral multityrosine kinase inhibitor of MET, AXL and VEGF receptors
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Arpita Desai and Eric J. Small
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0301 basic medicine ,Cancer Research ,Cabozantinib ,Tumor suppressor gene ,Pyridines ,Administration, Oral ,urologic and male genital diseases ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,Proto-Oncogene Proteins ,Humans ,Medicine ,Anilides ,Receptor ,Carcinoma, Renal Cell ,Protein Kinase Inhibitors ,neoplasms ,Neoplasm Staging ,Clinical Trials as Topic ,business.industry ,Kinase ,Receptor Protein-Tyrosine Kinases ,General Medicine ,Proto-Oncogene Proteins c-met ,medicine.disease ,Axl Receptor Tyrosine Kinase ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,Receptors, Vascular Endothelial Growth Factor ,Treatment Outcome ,030104 developmental biology ,Oncology ,chemistry ,Von Hippel-Lindau Tumor Suppressor Protein ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Signal transduction ,business ,Carcinogenesis ,Tyrosine kinase ,Signal Transduction - Abstract
Von Hippel–Lindau ( VHL), a tumor suppressor gene, is frequently inactivated in renal cell carcinoma (RCC). It drives tumorigenesis by activating downstream hypoxia responsive genes and proangiogenic factors like VEGFR, and is responsible for the activity of tyrosine kinase inhibitors in RCC. Resistance to VEGFR therapy eventually occurs, in part due to activation of alternative signaling pathways like AXL and MET. Cabozantinib is a potent inhibitor of VEGF, AXL and MET receptors providing rationale for its use in RCC. Cabozantinib has been approved for use in the first- and second-line setting in patients with advanced RCC. This manuscript reviews the preclinical data, pharmacology, clinical efficacy and safety of the use of cabozantinib in RCC.
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- 2019
18. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy
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Betsy Morrow, Ming K. Lee, Jun Wei, Anish Thomas, Liqiang Xi, Raffit Hassan, Idrees Mian, Mary Claire King, Tom Walsh, Jingli Zhang, Snehal Patel, Vasiliki Panou, David S. Schrump, Jane E. Churpek, Arpita Desai, Mark Raffeld, Emerson Padiernos, Javed Khan, Meghana Gadiraju, Shaojian Gao, Kathleen A. Calzone, Mary Hesdorffer, Suleyman Gulsuner, Christine Alewine, Seth M. Steinberg, and Hedy L. Kindler
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Adult ,Male ,Mesothelioma ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,DNA Repair ,DNA repair ,Pleural Neoplasms ,medicine.disease_cause ,Young Adult ,Survival ,Prostate ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genotype ,medicine ,Humans ,BAP1 ,Genetic Predisposition to Disease ,Gene ,Germ-Line Mutation ,Aged ,Platinum ,Aged, 80 and over ,Mutation ,Multidisciplinary ,DNA repair genes ,business.industry ,Tumor Suppressor Proteins ,Nherited genetics ,Mesothelioma, Malignant ,Biological Sciences ,Middle Aged ,medicine.disease ,Survival Analysis ,respiratory tract diseases ,medicine.anatomical_structure ,Peritoneal mesothelioma ,Female ,business ,Ubiquitin Thiolesterase - Abstract
Survival from malignant mesothelioma, particularly pleural mesothelioma, is very poor. For patients with breast, ovarian, or prostate cancers, overall survival is associated with increased sensitivity to platinum chemotherapy due to loss-of-function mutations in DNA repair genes. The goal of this project was to evaluate, in patients with malignant mesothelioma, the relationship between inherited loss-of-function mutations in DNA repair and other tumor suppressor genes and overall survival following platinum chemotherapy. Patients with histologically confirmed malignant mesothelioma were evaluated for inherited mutations in tumor suppressor genes. Survival was evaluated with respect to genotype and site of mesothelioma. Among 385 patients treated with platinum chemotherapy, median overall survival was significantly longer for patients with loss-of-function mutations in any of the targeted genes compared with patients with no such mutation (P = 0.0006). The effect of genotype was highly significant for patients with pleural mesothelioma (median survival 7.9 y versus 2.4 y, P = 0.0012), but not for patients with peritoneal mesothelioma (median survival 8.2 y versus 5.4 y, P = 0.47). Effect of patient genotype on overall survival, measured at 3 y, remained independently significant after adjusting for gender and age at diagnosis, two other known prognostic factors. Patients with pleural mesothelioma with inherited mutations in DNA repair and other tumor suppressor genes appear to particularly benefit from platinum chemotherapy compared with patients without inherited mutations. These patients may also benefit from other DNA repair targeted therapies such as poly-ADP ribose polymerase (PARP) inhibitors.
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- 2019
19. An interplay between spacer nature and alkyl chain length on aqueous micellar properties of cationic Gemini surfactants: A multi-technique approach
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Kushan Parikh, Sneha Singh, Arpita Desai, and Sanjeev Kumar
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chemistry.chemical_classification ,Aqueous solution ,Aggregation number ,Conductometry ,Chemistry ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Krafft temperature ,Micelle ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,Dynamic light scattering ,Critical micelle concentration ,Materials Chemistry ,Physical chemistry ,Physical and Theoretical Chemistry ,0210 nano-technology ,Spectroscopy ,Alkyl - Abstract
Micellar parameters (critical micelle concentration (cmc), degree of micellar ionization (α), Krafft temperature (Tk), micro-polarity, aggregation number (Nagg) and dielectric constant (ea)) of aqueous cationic geminis (denoted as m-s-m; where, m = 12 or 14 and s = polymethylene, diester, diamido or diester isosorbate) have been studied by multi-technique approach (conductometry, fluorescence and 1H NMR) and compared with alkyltrimethylammonium bromide (CmTAB). Geminis show lower cmc and Tk than CmTAB. Among the geminis, hydrophilic spacer containing geminis show even lower cmc and Tk than the polymethylene spacer geminis. Temperature dependence of cmc shows a decrease, constancy followed by an increase (U-shaped behaviour) as s or m changes. Thermodynamic parameters have been obtained by temperature dependence of cmc. Intra-micellar monomeric arrangement and micellar size information have been acquired by 2D NOESY/COSY 1H NMR and dynamic light scattering (DLS), respectively. Data suggest that the hydrophilic spacer based geminis produce compact micelles with higher polarity compared to polymethylene spacer geminis (or CmTAB). The approach might be employed to tune the micellar interior environment/size, by changing the nature of the spacer or m.
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- 2019
20. Mixed micellization/clouding assisted solubilization of polycyclic aromatic hydrocarbon: Potential in environmental remediation
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Sneha Singh, Sanjeev Kumar, Sanjay Kumar Yadav, Sandhya Dixit, Arpita Desai, and Kushan Parikh
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chemistry.chemical_classification ,Anthracene ,Inorganic chemistry ,Polycyclic aromatic hydrocarbon ,02 engineering and technology ,Fluorene ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Micelle ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,Hydrophobic effect ,chemistry.chemical_compound ,chemistry ,Critical micelle concentration ,Materials Chemistry ,Pyrene ,Physical and Theoretical Chemistry ,Solubility ,0210 nano-technology ,Spectroscopy - Abstract
Micellization and clouding behaviors of an anionic gemini surfactant, phosphoric acid, P, P′‑1,4‑butanedieyl P, P′‑didodecyl ester, disodium salt (12-4-12A), in aqueous solution, have been investigated in the presence of a surface active ionic liquid (SAIL), tetra n‑pentylammonium bromide (TPeAB). Critical micelle concentration and 1H NMR data show synergistic interactions/intercalation of n‑pentyl chain between the 12-4-12A monomers constituting the micelle, respectively. 12-4-12A + TPeAB system showed the cloud point (CP) at distinctly lower [12-4-12A]. Amino acid/cyclodextrin has been used to tune the CP. DLS and TEM data suggest the formation of n‑pentyl chain (of the SAIL) mediated linked aggregates whose size decreases with lowering [TPeAB] while compactness increases by β-CD. POM data showed that larger aggregates are formed near the CP. This may be due to increased hydrophobic interactions (between dodecyl chains of the gemini and pentyl chains of the TPeAB) and decreased electrostatic repulsion (as indicated by lowering zeta-potential value at CP). Mixtures, with or without β-CD, are used for solubilization/co‑solubilization of polyaromatic hydrocarbon (PAHs-anthracene, pyrene or fluorene). Molar solubilization ratio (MSR) has been computed using UV–Visible spectrophotometry. The percentage MSR value increases in order: Anthracene > Pyrene > Fluorene in comparison to pure 12-4-12A. Cloud point extraction of anthracene shows that it concentrates ~93% in surfactant rich phase (SRP). However, anthracene content decreases (~80%) when the system contains β-CD. GZrO2 nanocomposite has shown nearly complete adsorption of anthracene. Strategies, like mixed micellization, tuning of clouding and co-solubilization, can enhance solubility/bioavailability, extraction and subsequent degradation of PAHs from the aquatic/soil environment.
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- 2018
21. Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort
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Mehmet Asim Bilen, Jodi Lyn Layton, Whitley Hatton, Hamid Emamekhoo, Vadim S. Koshkin, Patrick Cotogno, Arpita Desai, Ellen Jaeger, Oliver Sartor, Charlotte Manogue, Pedro C. Barata, Brian E. Lewis, Arnab Basu, Deepak Kilari, and Malcolm Light
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cancer Research ,Chromophobe cell ,Gastroenterology ,metastatic renal cell carcinoma ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Adverse effect ,Lymph node ,Original Research ,business.industry ,Acute kidney injury ,PD-1/PD-L1 inhibitor ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Clinical trial ,030104 developmental biology ,medicine.anatomical_structure ,Tolerability ,Oncology ,030220 oncology & carcinogenesis ,monotherapy ,Cohort ,immunotherapy ,business ,first-line treatment - Abstract
Introduction: The treatment landscape of metastatic renal cell carcinoma has advanced significantly with the approval of combination regimens containing an immune checkpoint inhibitor (ICI) for patients with treatment-naive disease. Little information is available regarding the activity of single-agent ICIs for patients with previously untreated mRCC not enrolled in clinical trials. Methods: This retrospective, multicenter cohort included consecutive treatment-naive mRCC patients from six institutions in the United States who received ≥1 dose of an ICI outside a clinical trial, between June 2017 and October 2019. Descriptive statistics were used to analyze outcomes including objective best response rate (ORR), progression-free survival (PFS), and tolerability. Results: The final analysis included 27 patients, 70% men, median age 64 years (range 42-92), 67% Caucasian, and 33% with ECOG 2 or 3 at baseline. Most patients had intermediate risk (85%, IMDC) with clear cell (56%), papillary (26%), unclassified (11%), chromophobe (4%), and translocation (4%) RCC. All patients had evidence of metastatic disease involving the lungs (59%), lymph node (41%), CNS (19%), liver (11%), adrenal gland (11%), and bone (11%). The median time on ICI was 3.1 (0.1-26.8) months, and the median PFS was 6.3 (95% CI, 0-18.6) months. Among the 21 patients with an evaluable response, the best ORR was 33%, including two complete responses and five partial responses. The ORR was 29% (n = 1 complete response, n = 5 partial response) in clear cell and 5% (n = 1 complete response) in non-clear cell RCC. Adverse events (AEs) of any cause were reported in 37% and included fatigue (11%), dermatitis (11%), diarrhea (7%), and shortness of breath (7%). Significant AEs (30%) included shortness of breath (7%), acute kidney injury (4%), dermatitis (4%), Clostridium difficile infection (4%), cerebrovascular accident (4%), and fatigue (7%). Three patients discontinued therapy due to grade 4 AEs. Conclusions: In this multi-institutional case series, single-agent ICI demonstrated objective responses and was well tolerated in a heterogeneous treatment-naive mRCC cohort. ICI monotherapy is not the standard of care for patients with mRCC, and further investigation is necessary to explore predictive biomarkers for optimal treatment selection in this setting.
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- 2020
22. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021
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Robert J, Motzer, Eric, Jonasch, Shawna, Boyle, Maria I, Carlo, Brandon, Manley, Neeraj, Agarwal, Ajjai, Alva, Katy, Beckermann, Toni K, Choueiri, Brian A, Costello, Ithaar H, Derweesh, Arpita, Desai, Saby, George, John L, Gore, Naomi, Haas, Steven L, Hancock, Christos, Kyriakopoulos, Elaine T, Lam, Clayton, Lau, Bryan, Lewis, David C, Madoff, Brittany, McCreery, M Dror, Michaelson, Amir, Mortazavi, Lakshminarayanan, Nandagopal, Phillip M, Pierorazio, Elizabeth R, Plimack, Lee, Ponsky, Sundhar, Ramalingam, Brian, Shuch, Zachary L, Smith, Bradley, Somer, Jeffrey, Sosman, Mary A, Dwyer, and Angela D, Motter
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Humans ,Genetic Testing ,Carcinoma, Renal Cell ,Kidney Neoplasms ,Article - Abstract
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.
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- 2020
23. Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer
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Vadim S. Koshkin, Arpita Desai, Anobel Y. Odisho, Alexander Bell, Tracy Kuo Lin, Thomas A. Hope, Sylvia Zhang, Kalin Werner, Matthew D. Bucknor, Nichole Legaspi, and Hala T. Borno
- Subjects
0301 basic medicine ,Oncology ,Glutamate Carboxypeptidase II ,Male ,Cancer Research ,Aging ,Time Factors ,Logistic regression ,Prostate cancer ,0302 clinical medicine ,Pregnancy ,Bayesian multivariate linear regression ,80 and over ,biochemical recurrence ,Medicine ,Cancer ,Original Research ,disparities ,Receipt ,Aged, 80 and over ,screening and diagnosis ,Prostate Cancer ,Health Care Costs ,Middle Aged ,Prognosis ,prostate cancer ,medical oncology ,Surface ,Detection ,Molecular Diagnostic Techniques ,Health ,030220 oncology & carcinogenesis ,Antigens, Surface ,Pacific islanders ,Biomedical Imaging ,Female ,Kallikreins ,Cohort study ,Biochemical recurrence ,Urologic Diseases ,medicine.medical_specialty ,Oncology and Carcinogenesis ,03 medical and health sciences ,Insurance ,Clinical Research ,Predictive Value of Tests ,Internal medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Antigens ,Healthcare Disparities ,Aged ,Retrospective Studies ,Insurance, Health ,business.industry ,Prostatic Neoplasms ,Clinical Cancer Research ,Prostate-Specific Antigen ,medicine.disease ,molecular imaging ,4.1 Discovery and preclinical testing of markers and technologies ,030104 developmental biology ,Good Health and Well Being ,Positron-Emission Tomography ,Biochemistry and Cell Biology ,Molecular imaging ,business - Abstract
Background Molecular imaging with novel radiotracers is changing the treatment landscape in prostate cancer (PCa). Currently, standard of care includes either conventional and molecular imaging at time of biochemical recurrence (BCR). This study evaluated the determinants of and cost associated with utilization of molecular imaging for BCR PCa. Methods This is a retrospective observational cohort study among men with BCR PCa from June 2018 to May 2019. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET and Prostate Specific Membrane Antigen PET) as part of diagnostic work‐up for BCR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost within a 1‐year time frame. Results The study sample included 234 patients; 79.1% White, 2.1% Black, 8.5% Asian/Pacific Islander, and 10.3% Other. The majority were 55 years or older (97.9%) and publicly insured (74.8%). Analysis indicated a one‐unit reduction in PSA is associated with 1.3 times higher likelihood of receiving molecular imaging (p, This study evaluated the determinants of and cost associated with utilization of molecular imaging for biochemically recurrent prostate cancer. Higher prostate‐specific antigen level was associated with lower likelihood for molecular imaging and higher cost in a 1‐year timeframe.
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- 2020
24. Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma
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David Fischer, Arthur Wolin, Dezheng Huo, Viswateja Nelakuditi, Buerkley Rose, Zejuan Li, Aliya N. Husain, Arpita Desai, Lauren L. Ritterhouse, Amy K. Johnson, Maria Helgeson, Kiran K. Turaga, Jeremy P. Segal, Oluf Dimitri Røe, Jyoti D. Patel, Sabah Kadri, Emily Skarda, Hedy L. Kindler, Caroline M. Weipert, Vasiliki Panou, Meghana Gadiraju, Shannon R Zhang, Madison Weatherly, Jane E. Churpek, and Nanna Helen Sulai
- Subjects
Adult ,Male ,Mesothelioma ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,DNA damage ,Germline ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Germ-Line Mutation ,Aged ,Aged, 80 and over ,BAP1 ,business.industry ,Mesothelioma, Malignant ,Tunica vaginalis ,High-Throughput Nucleotide Sequencing ,Odds ratio ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business - Abstract
Purpose The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM). Methods We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM. Results Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54). Conclusion A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.
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- 2018
25. FGFR Signaling as a Target for Lung Cancer Therapy
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Arpita Desai and Alex A. Adjei
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Antineoplastic Agents ,Fibroblast growth factor ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Humans ,FGFR inhibitors ,Medicine ,Molecular Targeted Therapy ,Receptor ,Lung cancer ,business.industry ,medicine.disease ,Receptors, Fibroblast Growth Factor ,FGFR pathway ,Cell biology ,Review article ,FGFR abberations ,030104 developmental biology ,Oncology ,Fibroblast growth factor receptor ,030220 oncology & carcinogenesis ,Cancer research ,Signal transduction ,business ,Carcinogenesis ,Function (biology) ,Signal Transduction - Abstract
Lung cancer is the leading cause of cancer-related death in developed countries. Recently, molecular targeted therapies have shown promising results in the management of lung cancer. These therapies require a clear understanding of the relevant pathways that drive carcinogenesis and maintenance of the malignant phenotype. The fibroblast growth factor receptor (FGFR) signaling axis is one such pathway that plays a central role in normal cellular function. Alterations in this pathway have been found in many cancers. In this review article, we focus on the role of this pathway in lung cancer. We present the molecular structure of FGFR, the interaction of the receptor with its ligands (the fibroblast growth factors), its downstream signaling, and aberrations in the FGFR pathway. We also discuss clinical trials involving selective and multikinase FGFR inhibitors in lung cancer treatment.
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- 2016
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26. 769P APOBEC signatures and high tumour mutational burden as predictors of clinical outcomes and response to therapy in patients with urothelial carcinoma
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James P. Grenert, Vadim S. Koshkin, Patrick Devine, Henry J Martell, Sarah E. Umetsu, Eric J. Small, Lawrence Fong, Arpita Desai, Divya Natesan, Terence W. Friedlander, Li Zhang, J. Van Ziffle, Boris C. Bastian, Jonathan Chou, Bradley A. Stohr, Sima P. Porten, Nancy M. Joseph, A. Sweet-Cordero, Courtney Onodera, and Emily Chan
- Subjects
Oncology ,APOBEC ,medicine.medical_specialty ,Response to therapy ,business.industry ,Internal medicine ,Medicine ,In patient ,Hematology ,business ,Urothelial carcinoma - Published
- 2020
27. Metal-free synthesis of calixsalen-type cavitands for the recognition of fluoride ion
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Arpita Desai and Dharti Rana
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chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Substituent ,Salt (chemistry) ,Cavitand ,Ethylenediamine ,010402 general chemistry ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Polymer chemistry ,Polar effect ,Nitro ,Fluoride - Abstract
Novel calixsalen-type cavitands have been synthesized using metal-free synthesis from simple and inexpensive materials, such as ethylenediamine and 5,5′-methylene-bis-salicylaldehyde derivatives. The cavitand 1 containing salen functionality recognizes fluoride ion. Fluoride ions switch on fluorescence on binding with the cavitand 1. Substitution on bis-salicylaldehyde part of calixsalen-type cavitand shows change in recognition behavior. On the attachment of electron withdrawing substituent, such as nitro group, the cavitand lost its fluorescence properties but proved to be a better colorimetric probe showing marked color change from pale yellow to red on addition of tetrabutyl ammonium salt of fluoride ion to the solution of cavitand. The nitro substituted cavitand is highly sensitive and selective for fluoride anion and hence is a promising candidate for development of colorimetric chemosensor. The binding of the cavitands with fluoride ion is investigated using 1H NMR-titration experiments.
- Published
- 2018
- Full Text
- View/download PDF
28. PS02.23 CCDC6-RET Fusion as a Mechanism of Acquired EGFR Resistance
- Author
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Jeremy P. Segal, Livia Szeto, Arpita Desai, Jyoti D. Patel, and Everett E. Vokes
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Mechanism (biology) ,business.industry ,Internal medicine ,medicine ,RET Fusion ,Intensive care medicine ,business - Published
- 2017
29. Epithelial ovarian cancer: An overview
- Author
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Avinash Reddy, Chika Okoli, Ravipati Hariprasad, Kartik Aysola, Geary Franklin, Veena Rao, Edward E. Partridge, William E. Grizzle, Ugorji Chinemerem, Anachebe Ngozi, Omar K. Danner, Guilherme Cantuaria, Yunlong Qin, Charles N. Landen, Karan P. Singh, Valerie Montgomery Rice, E. Shyam P. Reddy, Candace Gates, Jingyao Xu, and Arpita Desai
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,Pathology ,endocrine system ,endocrine system diseases ,business.industry ,medicine.medical_treatment ,medicine.disease ,Gynecological cancer ,female genital diseases and pregnancy complications ,Article ,Breast cancer ,Current management ,Ovarian carcinoma ,Internal medicine ,medicine ,Epithelial ovarian cancer ,business ,Ovarian cancer ,Cause of death - Abstract
Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions.
- Published
- 2014
30. Pneumonectomy-Sparing NSAID Therapy for Pulmonary Inflammatory Myofibroblastic Tumor
- Author
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Todd L. Demmy, Arpita Desai, Saraswati Pokharel, Grace K. Dy, and Sofia Ghani
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,business.industry ,medicine.medical_treatment ,Anti-Inflammatory Agents, Non-Steroidal ,Middle Aged ,Surgery ,Pneumonectomy ,Neoplasms, Muscle Tissue ,Oncology ,Medicine ,Humans ,Female ,business - Published
- 2015
- Full Text
- View/download PDF
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