Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer.

Background: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. Objectives: We quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. Methods: A retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. Results: Black race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. Conclusions: Black patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.

Training Hematologists/Oncologists for the Academic-Community Hybrid: Creating a Fellowship Framework for the Future.

PURPOSE: Conventional hematology/oncology fellowship training is designed to foster careers in academic practice through intensive exposure to clinical and laboratory research. Even so, a notable proportion of graduating fellows opt to pursue a clinically focused career outside the realm of academic medicine. Given the corresponding shortage of oncologists in nonurban and rural settings, improving the representation of hematologists/oncologists in the community setting is a national priority. METHODS: We reviewed current national challenges and changing models of cancer care delivery in the context of the traditional academic training model along with trends in practice patterns for recent hematology/oncology graduates. We defined the Academic-Community hybrid (ACH) and how it supports the evolution in contemporary models of cancer care. We then drew on the authors' experiences to formulate an innovative goal-concordant training paradigm for fellows seeking careers in the ACH model. RESULTS: The ACH hematology/oncology fellowship training pathway emphasizes and optimizes professional development domains including clinical care, patient safety and quality improvement, business and operations, cancer care equity and community access, healthy policy and alignment with professional organizations, and medical education. CONCLUSION: This novel hematology/oncology training model provides a paradigm for optimizing preparedness for practice in an increasingly complex cancer care delivery environment while addressing workforce shortages and health disparities.

An up-to-date evaluation of abiraterone for the treatment of prostate cancer.

Introduction: Abiraterone acetate, an oral 17-alpha-hydroxylase inhibitor, effectively prevents the synthesis of androgens from steroid precursors. Abiraterone has become a standard of care in patients with metastatic prostate cancer due to its efficacy in both castrate-sensitive and castrate-resistant disease when given in combination with androgen deprivation therapy (ADT). Abiraterone may have a role in additional aspects of prostate cancer treatment in the future.Areas covered: The present article focuses on the development and establishment of abiraterone among the available treatment options for prostate cancer. A literature search was performed in PubMed/Medline for prior studies and reviews of the drug. Current clinical trials were examined in the Clinicaltrials.gov database.Expert opinion: Abiraterone has shown efficacy in castrate-resistant metastatic prostate cancer, providing an additional degree of hormonal sensitivity for tumors resistant to ADT. Impressively, abiraterone in conjunction with ADT as a first-line treatment for castrate-sensitive prostate cancer also confers a significant overall survival benefit compared to ADT alone. With minimal additional toxicity, abiraterone has established itself as a well-tolerated, convenient, and effective treatment option. Ongoing studies are expected to broaden the drug's indications as well as its preference among other prostate cancer therapies.

Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program.

The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program's response to the demands of COVID-19 during this uncertain time in health care.

EGFR-Mutated Lung Cancers Resistant to Osimertinib through EGFR C797S Respond to First-Generation Reversible EGFR Inhibitors but Eventually Acquire EGFR T790M/C797S in Preclinical Models and Clinical Samples.

INTRODUCTION: Osimertinib is approved for advanced EGFR-mutated NSCLC, and identification of on-target mechanisms of resistance (i.e., EGFR C797S) to this third-generation EGFR inhibitor are evolving. Whether durable control of subsequently osimertinib-resistant NSCLC with the EGFR-sensitizing mutation (SM)/C797S is possible with first-generation EGFR inhibitors (such as gefitinib or erlotinib) remains underreported, as does the resultant acquired resistance profile. METHODS: We used N-ethyl-N-nitrosourea mutagenesis to determine the profile of EGFR SM/C797S preclinical models exposed to reversible EGFR inhibitors. In addition, we retrospectively probed a case of EGFR SM lung adenocarcinoma treated with first-line osimertinib, followed by second-line erlotinib in the setting of EGFR SM/C797S. RESULTS: Use of N-ethyl-N-nitrosourea mutagenesis against the background of EGFR L858R/C797S in conjunction with administration of gefitinib revealed preferential outgrowth of cells with EGFR L858R/T790M/C797S. A patient with EGFR delE746_T751insV NSCLC was treated with osimertinib with sustained response for 10 months before acquiring EGFR C797S. The patient was subsequently treated with erlotinib, with response for a period of 4 months, but disease progression ensued. Liquid biopsy disclosed EGFR delE746_T751insV with T790M and C797S present in cis. CONCLUSION: EGFR SM NSCLC can acquire resistance to osimertinib through development of the EGFR C797S mutation. In this clinical scenario, the tumor may respond transiently to reversible first-generation EGFR inhibitors (gefitinib or erlotinib), but evolving mechanisms of on-target resistance-in clinical specimens and preclinical systems-indicate that EGFR C797S along with EGFR T790M can evolve. This report adds to the growing understanding of tumor evolution or adaptability to sequential EGFR inhibition and augments support for exploring combination therapies to delay or prevent on-target resistance.