MedStar Georgetown University Hospital

About: MedStar Georgetown University Hospital is a healthcare organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Medicine & Population. The organization has 1760 authors who have published 2175 publications receiving 22883 citations. The organization is also known as: Georgetown University Hospital.

Predictive biomarkers for checkpoint inhibitor-based immunotherapy.

Abstract: The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination approaches. The greatest focus has been on tumour-cell PD-L1 expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. In this Review, we discuss the status of PD-L1 testing and explore emerging data on new biomarker strategies with tumour-infiltrating lymphocytes, mutational burden, immune gene signatures, and multiplex immunohistochemistry. Future development of an effective predictive biomarker for checkpoint inhibitor-based immunotherapy will integrate multiple approaches for optimal characterisation of the immune tumour microenvironment.

Quality of Life and Burnout Rates Across Surgical Specialties: A Systematic Review.

Abstract: Importance Establishing strategies to minimize the burden of burnout and poor quality of life (QOL) on surgeons relies on a thorough understanding of QOL and burnout among the various surgical specialties. Objectives To systematically review the literature across multiple surgical specialties and provide a comprehensive understanding of QOL and burnout among all surgeons, to delineate variation in rates of burnout and poor QOL, and to elucidate factors that are commonly implicated in these outcomes. Evidence Review An OVID electronic search encompassing MEDLINE, PsycInfo, and EMBASE was completed using the following MeSH search terms: quality of life , burnout , surgeon , surgical specialty , and United States . Full articles published in English from January 1, 1980, to June 10, 2015, that evaluated US surgical specialists and included more than 1 question related to QOL were included. Review articles and evaluations that included medical students or nonsurgical health care professionals were excluded. Of 1420 titles, 41 articles met these criteria. The standardized methodologic principles of PRISMA for reporting systematic reviews guided analysis. Primary end points were QOL scores and burnout rates that compared sex, age, level of training (resident vs attending), surgical specialty, and the type of assessment tool. Secondary outcomes included proposed work hours and income as factors contributing to burnout. Owing to the heterogeneity of data reporting among articles, qualitative analysis was also reported. Findings Of the 16 specialties included, pediatric (86% to 96%) and endocrine (96%) surgeons demonstrated the highest career satisfaction, whereas a portion of plastic surgeons (33%) and vascular surgeons (64%) were least satisfied. The effect of sex was variable. Residents demonstrated a significantly higher risk for burnout than attending surgeons across multiple specialties, including obstetrics and gynecology, otolaryngology, and orthopedic surgery. One-third of the studies found hours worked per week to be a statistically significant predictor of burnout, decreased career satisfaction, and poorer QOL. Conclusions and Relevance Burnout and QOL vary across all surgical specialties. Whether sex affects burnout rates remains unclear. Residents are at an increased risk for burnout and more likely to report a poor QOL than attending surgeons.

Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer.

Abstract: Importance Poly(adenosine diphosphate-ribose) polymerase inhibitor and anti-programmed death receptor-1 inhibitor monotherapy have shown limited clinical activity in patients with advanced triple-negative breast cancer (TNBC). Objective To evaluate the clinical activity (primary) and safety (secondary) of combination treatment with niraparib and pembrolizumab in patients with advanced or metastatic TNBC. Design, setting, and participants This open-label, single-arm, phase 2 study enrolled 55 eligible patients with advanced or metastatic TNBC irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression at 34 US sites. Data were collected from January 3, 2017, through October 29, 2018, and analyzed from October 29, 2018, through February 27, 2019. Interventions Patients were administered 200 mg of oral niraparib once daily in combination with 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle. Main outcomes and measures The primary end point was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points were safety, disease control rate (DCR; complete response plus partial response plus stable disease), duration of response (DOR), progression-free survival (PFS), and overall survival. Results Within the full study population of 55 women (median age, 54 years [range, 32-90 years]), 5 patients had confirmed complete responses, 5 had confirmed partial responses, 13 had stable disease, and 24 had progressive disease. In the efficacy-evaluable population (n = 47), ORR included 10 patients (21%; 90% CI, 12%-33%) and DCR included 23 (49%; 90% CI, 36%-62%). Median DOR was not reached at the time of the data cutoff, with 7 patients still receiving treatment at the time of analysis. In 15 evaluable patients with tumor BRCA mutations, ORR included 7 patients(47%; 90% CI, 24%-70%), DCR included 12 (80%; 90% CI, 56%-94%), and median PFS was 8.3 months (95% CI, 2.1 months to not estimable). In 27 evaluable patients with BRCA wild-type tumors, ORR included 3 patients (11%; 90% CI, 3%-26%), DCR included 9 (33%; 90% CI, 19%-51%), and median PFS was 2.1 months (95% CI, 1.4-2.5 months). The most common treatment-related adverse events of grade 3 or higher were anemia (10 [18%]), thrombocytopenia (8 [15%]), and fatigue (4 [7%]). Immune-related adverse events were reported in 8 patients (15%) and were grade 3 in 2 patients (4%); no new safety signals were detected. Conclusions and relevance Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations. The combination therapy was safe with a tolerable safety profile, warranting further investigation. Trial registration ClinicalTrials.gov identifier: NCT02657889.