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vamsidhar velcheti

Monica Khunger, Prantesh Jain, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors...
January 10, 2018: Clinical Lung Cancer
Pradnya D Patil, Mauricio Burotto, Vamsidhar Velcheti
Immune checkpoint pathways are key immune regulatory pathways that play a physiologic role in maintaining immune-homeostasis and are often co-opted by cancer cells to evade the host immune system. Recent developments in cancer immunotherapy, mainly drugs blocking the immune checkpoint pathways, have revolutionized the treatment paradigm for many solid tumors. A wide spectrum of immune-related adverse events (irAEs) have been described with the use of these agents which necessitate treatment with immunosuppression, leading to disruption of therapy and can on occasion be life-threatening...
February 10, 2018: Expert Review of Molecular Diagnostics
Prantesh Jain, Chhavi Jain, Vamsidhar Velcheti
Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer...
January 2018: Therapeutic Advances in Respiratory Disease
Rajat Thawani, Michael McLane, Niha Beig, Soumya Ghose, Prateek Prasanna, Vamsidhar Velcheti, Anant Madabhushi
Lung cancer is responsible for a large proportion of cancer-related deaths across the globe, with delayed detection being perhaps the most significant factor for its high mortality rate. Though the National Lung Screening Trial argues for screening of certain at-risk populations, the practical implementation of these screening efforts has not yet been successful and remains in high demand. Radiomics refers to the computerized extraction of data from radiologic images, and provides unique potential for making lung cancer screening more rapid and accurate using machine learning algorithms...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel Sanmamed, Vamsidhar Velcheti, Konstantinos Syrigos, Maria Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human non-small cell lung cancer (NSCLC). Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T cells, CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Vamsidhar Velcheti, Nathan A Pennell
Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice...
September 2017: Annals of Translational Medicine
Xiangxue Wang, Andrew Janowczyk, Yu Zhou, Rajat Thawani, Pingfu Fu, Kurt Schalper, Vamsidhar Velcheti, Anant Madabhushi
Identification of patients with early stage non-small cell lung cancer (NSCLC) with high risk of recurrence could help identify patients who would receive additional benefit from adjuvant therapy. In this work, we present a computational histomorphometric image classifier using nuclear orientation, texture, shape, and tumor architecture to predict disease recurrence in early stage NSCLC from digitized H&E tissue microarray (TMA) slides. Using a retrospective cohort of early stage NSCLC patients (Cohort #1, n = 70), we constructed a supervised classification model involving the most predictive features associated with disease recurrence...
October 19, 2017: Scientific Reports
Daniel E Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A Schalper, David L Rimm
BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC)...
October 17, 2017: Journal for Immunotherapy of Cancer
Marc S Ernstoff, Shipra Gandhi, Manu Pandey, Igor Puzanov, Petros Grivas, Alberto Montero, Vamsidhar Velcheti, Mary Jo Turk, Claudia Marcela Diaz-Montero, Lionel D Lewis, Carl Morrison
In 1996, Jim Allison demonstrated that blocking the immune regulatory molecule CTLA-4 with anit-CTLA4 antibody led to enhance tumor responses in mice. It would take an additional 15 years for human studies to confirm the potency and clinical efficacy of anti-CTLA4, ultimately leading to US FDA approval of the first checkpoint inhibitor, ipilimumab. Now with a plethora of immune-modulating agents demonstrating single agent safety and benefit across many tumor types, investigation on the optimal combination of immune-based therapies has begun in earnest...
August 2017: Future Oncology
Min Huang, Yanyan Lou, James Pellissier, Thomas Burke, Frank Xiaoqing Liu, Ruifeng Xu, Vamsidhar Velcheti
OBJECTIVES: Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. METHODS: We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years...
August 2017: PharmacoEconomics
Vamsidhar Velcheti, Tomas Radivoyevitch, Yogen Saunthararajah
Searches for effective yet nontoxic oncotherapies are searches for exploitable differences between cancer and normal cells. In its core of cell division, cancer resembles normal life, coordinated by the master transcription factor MYC. Outside of this core, apoptosis and differentiation programs, which dominantly antagonize MYC to terminate cell division, necessarily differ between cancer and normal cells, as apoptosis is suppressed by biallelic inactivation of the master regulator of apoptosis, p53, or its cofactor p16/CDKN2A in approximately 80% of cancers...
2017: American Society of Clinical Oncology Educational Book
Monica Khunger, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, Peter Mazzone, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
BACKGROUND: Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use...
August 2017: Chest
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Mehdi Alilou, Niha Beig, Mahdi Orooji, Prabhakar Rajiah, Vamsidhar Velcheti, Sagar Rakshit, Niyoti Reddy, Michael Yang, Frank Jacono, Robert C Gilkeson, Philip Linden, Anant Madabhushi
PURPOSE: Distinguishing between benign granulmoas and adenocarcinomas is confounded by their similar visual appearance on routine CT scans. Unfortunately, owing to the inability to discriminate these lesions radigraphically, many patients with benign granulomas are subjected to unnecessary surgical wedge resections and biopsies for pathologic confirmation of cancer presence or absence. This suggests the need for improved computerized characterization of these nodules in order to distinguish between these two classes of lesions on CT scans...
July 2017: Medical Physics
Katherine Glass, Alicia M Redden, Nathan A Pennell, James Stevenson, Vamsidhar Velcheti, Emily Van Wagoner, Chad W Cummings, Brian James Bolwell
29 Background: Patient-centered outcomes are important quality metrics of value-based cancer care. For NSCLC, these include chemotherapy administration within 30 days of death and end of life hospitalizations. Nivolumab was initially FDA approved in March 2015 for second-line therapy of squamous NSCLC and subsequently for non-squamous NSCLC. To evaluate the impact of post-approval nivolumab use on patient-centered outcomes, a retrospective review was performed of patients (pts) with metastatic NSLCC receiving nivolumab at TCI main campus and regional centers...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Leah M Pervere, Sagar Rakshit, Alexa B Schrock, Vincent A Miller, Siraj M Ali, Vamsidhar Velcheti
No abstract text is available yet for this article.
November 11, 2016: Clinical Lung Cancer
Mark A Socinski, Joan Schiller, Shaker Dakhil, Shayma Kazmi, Joseph Leach, Sylvia Hu, Sarah M Paul, David S Shames, See Phan, Cindy Yun, Vamsidhar Velcheti
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
Sai-Hong Ignatius Ou, Alexa B Schrock, Eduard V Bocharov, Samuel J Klempner, Carolina Kawamura Haddad, Gary Steinecker, Melissa Johnson, Barbara J Gitlitz, Jon Chung, Paulo V Campregher, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, James H Suh, Siraj M Ali, Vamsidhar Velcheti
INTRODUCTION: Erb-b2 receptor tyrosine kinase (HER2) transmembrane domain (TMD) mutations (HER2V659E , HER2G660D ) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown. METHODS: We prospectively analyzed 8551 consecutive lung adenocarcinomas using hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions...
March 2017: Journal of Thoracic Oncology
Charles D Sturgis, Dana Ataya, Benjamin C Calhoun, Vamsidhar Velcheti, Sanjay Mukhopadhyay
No abstract text is available yet for this article.
November 2016: Annals of the American Thoracic Society
Sameep Sehgal, Vamsidhar Velcheti, Sanjay Mukhopadhyay, James K Stoller
A 58-year-old woman with stage 4 adenocarcinoma of the lung being treated with pembrolizumab developed dyspnea, non-productive cough, and a right middle lobe infiltrate. Complete resolution of the infiltrate with cessation of pembrolizumab, initiation of prednisone and no antibiotic therapy suggested drug-associated lung toxicity as the cause. While the programmed death-1 (PD-1) inhibitors -pembrolizumab and nivolumab - have been implicated as a cause of diffuse or multifocal pulmonary infiltrates, the current case represents, to our knowledge, the first instance of a unilobar, focal infiltrate associated with their use...
2016: Respiratory Medicine Case Reports
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