Highlights of the NCCN Oncology Research Program

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The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program’s establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.

NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.

This feature highlights an NCCN study funded through the grant mechanism.

Investigating the Role of African Genetic Ancestry in Cardiovascular Complications and Cardiotoxicity Among Patients With Prostate Cancer Post Treatment With Androgen Deprivation Therapy

Principal Investigators: Camille Ragin, PhD, MPH; Daniel Geynisman, MD

Condition: Prostate cancer—quality of care

Institution: Fox Chase Cancer Center

This project leverages a strong multidisciplinary network of cancer, cardiovascular disease (CVD), cancer disparities, bioinformatics, and genetics/genomics experts with clinical and academic affiliations at the Temple University Health System (Fox Chase Cancer Center [FCCC] and Temple University Hospital [TUH]) and Temple University. Most team members have a long-standing history of prior research collaboration. We will also leverage a well-designed data warehouse infrastructure; the US National Death Index (NDI) and Census data; a large clinically annotated prostate cancer (PCa) database of close to 10,000 patients; and a recently established cohort of patients with PCa to test the hypothesis that African genetic ancestry increases the risk of preexisting CVD and cardiometabolic traits among Black patients with PCa and that metabolic syndrome (MetS) and increased atherosclerotic CVD (ASCVD) risk after initiation of androgen-deprivation therapy (ADT) is observed to a greater extent among Black patients versus White patients.

The scientific premise of the proposed research is based on our preliminary data and our review of the scientific literature, which demonstrate that (1) CVD-related death is more likely to occur among Black patients with PCa compared with White patients; (2) men treated with ADT are at increased risk of developing incident MetS, ASCVD, and cardiomyopathy, and that this risk is greater for men with preexisting CVD; (3) African-specific single-nucleotide polymorphisms (SNPs) have been shown to be associated with cardiometabolic disease and cardiometabolic traits, and that the role of African genetic ancestry in the contribution of CVD-related complications post-ADT has not been investigated; and (4) most of the scientific literature on ADT-related complications report studies conducted primarily in White men, and that racial disparities have not been inves2tigated. We propose a novel approach to addressing the gaps in the current literature that integrates molecular epidemiology and bioinformatics. We will generate novel data that could help increase understanding of the influence of ADT on the cardiovascular system and how therapy can affect men of different genetic and ancestral backgrounds.

We expect this work will inform strategies to improve individualized management and reduce disparities in survival and cardiotoxicity between Black and White patients with PCa. Unlike published studies, our analyses will consider contributions of genetic ancestry, socioeconomic status, and other confounders that often contribute to racial disparities in cancer. Furthermore, our novel approaches will investigate how genetic ancestry modulates these associations of ADT on CVD risk and cardiometabolic health concerns among patients with PCa.

Objective 1: Perform a retrospective analysis of clinical data to determine the association of race with MetS, CVD events, or ASCVD risk score prior to PCa diagnosis and compare the risk of CVD-specific death according to race. We will leverage the FCCC PCa urology database to match 1,264 Black patients to 3,792 White patients according to age, Gleason score or Grade group, neighborhood-level socioeconomic status, and insurance status in order to:

  • • Determine whether the risk of MetS, CVD events, or intermediate/high ASCVD risk score (ie, >7.4%) at the time of PCa diagnosis is higher for Black versus White patients.

  • • Determine whether the risk of CVD-specific death or increase in ACVD risk score after initiation of ADT is higher among Black versus White patients. Stratified analysis according to type of ADT will be performed if feasible.

Objective 2: Examine the impact of ADT on ASCVD risk, cardiometabolic outcomes, and cardiotoxicity by race and genetic ancestry. We will recruit Black and White patients with PCa who were diagnosed and treated at FCCC and TUH. We will collect data on biological, socioecological, treatment, health, ASCVD, and cardiometabolic status at baseline and at follow-up (every 12 months or when there is a change in treatment). We will:

  • • Use bioinformatics resources and tools to functionally characterize genome-wide ancestry-informative markers to identify SNPs that have a potential for high biological significance.

  • • Validate the functional contributions of African genetic ancestry markers by identifying African-specific SNPs associated with cardiotoxicity.

  • • Examine the association of ADT with ASCVD risk and cardiometabolic traits, such as blood pressure, body mass index, cholesterol, and waist circumference, among patient with PCa treated with and without ADT and determine whether African genetic ancestry modulates this association.

Contact: Camille Ragin, PhD, MPH • 215-728-1148 • Camille.Ragin@fccc.edu

For more information on specific trials, including patient selection criteria, use the contact information listed with each study.

For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, go to www.nccn.org/education-research/nccn-oncology-research-program/orp-main-page.

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