This proposal presents a five-year research career development program, focused on the prediction and prevention of life-threatening anthracycline chemotherapy cardiotoxicity in older adults with lymphoma through: 1) improved prediction tools, 2) analysis of current cardioprotection use and 3) ascertainment of patient and provider treatment preferences. The candidate is an Assistant Professor at Tufts University School of Medicine and the Medical Director of the Cardio-Oncology Program in the Division of Cardiology at Tufts Medical Center. Under the mentorship of Dr. David Kent and Dr. Susan Parsons, researchers in the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, the training plan builds on the candidate's prior clinical and research experience to develop expertise in 1) designing impactful cardio-oncology outcomes studies using large administrative databases; 2) oncology clinical trial design and 3) qualitative and decision analytic research methods. Each year in the US, more than 40,000 individuals 65 years and older are diagnosed with lymphoma with anthracycline-containing regimens recommended as first-line treatment in the majority of lymphoma subtypes. While anthracycline chemotherapeutic agents help induce lymphoma remission, they also increase the risk of heart failure (HF). These effects are worsened in older adults, as age is a potent risk factor for HF in both non-cancer and cancer populations. However, omission of anthracyclines, even in elderly patients at high risk of toxicity, may be associated with worse outcomes. Thus, strategies to better predict and prevent anthracycline cardiotoxicity are needed to improve outcomes in older patients with lymphoma. Small randomized trials in predominately non-lymphoma populations have identified several promising strategies to prevent HF in patients receiving anthracyclines; however, neither clinical practice guidelines nor the FDA endorse any of these therapies due to insufficient evidence for the prevention of HF in newly diagnosed adults with lymphoma. The objective of this proposal is to advance the science of anthracycline cardiotoxicity prediction and prevention by: 1) developing and validating a HF risk prediction model in older individuals with newly diagnosed lymphoma; 2) determining which cardioprotective strategies are currently used in practice and 3)eliciting treatment preferences for cardioprotection from patients and providers. This research will lead to improved knowledge of anthracycline cardiotoxicity prevention, provide preliminary data for a study of cardioprotection in high-risk individuals with lymphoma and provide the candidate with the necessary skills and experience to become a successful independent investigator.

Public Health Relevance

Anthracycline chemotherapeutic agents are commonly used in cancer treatment but can cause heart failure (HF), with older adults at increased risk. HF after anthracycline therapy has a poor prognosis and thus strategies to prevent anthracycline cardiotoxicity are needed. The proposed research will develop and externally validate a multivariable risk prediction model for HF in older adults with lymphoma, determine the utilization patterns of cardioprotective medications in routine clinical practice and elicit patient and provider preferences for cardioprotective strategies to support future clinical trials of cardioprotection in older adults with lymphoma.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
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Wang, Wayne C
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Tufts University
United States
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