Our overarching goal is to identify and characterize cancer patients at risk of developing cancer treatment- related cardiotoxicity and to mitigate cardiovascular dysfunction while optimizing cancer outcomes. Advances in early detection and treatment of cancer has improved 5-year survival. However, multi-modal cancer treatment often leads to cardiotoxicity. Cardiovascular disease (CVD) events during treatment can interfere with its delivery and thus lead to sub-optimal cancer outcomes and increased downstream morbidity, cost and mortality. American Heart Association (2019) guidelines recommend primary prevention with anti- hyperlipidemic and anti-hypertensive medication in high risk individuals, based on atherosclerotic cardiovascular disease (ASCVD) risk. However, it?s uncertain if primary prevention in cancer patients improves long-term CVD outcomes. American Society of Clinical Oncology (ASCO) (2017) guidelines has categorized high-dose anthracyclines, high dose radiation exposure to the heart, targeted therapy and certain combinations of these, as high cardiotoxic risk regimens. The impact of primary prevention in patients on high cardiotoxic risk regimens is unknown. ASCO guidelines also propose reduced radiation dosing, sequential treatment, liposomal formulations, and use of dexrazoxane as cardioprotective regimen strategies, but the long-term effect of these strategies has not been evaluated. To evaluate these questions, we will create a unique dataset by merging Kaiser Permanente (KP)?s electronic medical records with KP?s SEER cancer registry, and Social Security Administration (SSA)?s data, in a cohort of 25,000+ breast and lung cancer patients followed longitudinally for 5+years. We will risk stratify breast and lung cancer patients on ASCVD risk and evaluate the effect of primary prevention and cardioprotective regimens using advanced causal inference models exploring treatment effect heterogeneity from policy and decision-making perspectives. The study aims are:
Aim 1. Compare effectiveness of primary prevention on 1) the incidence of CVD during cancer treatment and 2) cancer and CVD outcomes post-treatment, in high ASCVD risk patients and high cardiotoxic risk regimens.
Aim 2. Evaluate the incremental economic impact of CVD in breast cancer and lung cancer patients & survivors and evaluate the incremental cost and cost-effectiveness of primary prevention.
Aim 3 : Compare effectiveness of cardio-protective oncology treatment strategies on 1) the incidence of CVD during cancer treatment and 2) cancer and CVD outcomes post-treatment, in high ASCVD risk patients. Completion of this proposal will answer the following crucial questions to improve patient outcomes (1) Does primary prevention prevent future CVD events, improve/optimize cancer treatment and outcomes, reduce disability and cost? (2) How many patients need to be treated to avoid one cardiovascular or cancer outcome? (2) What are the long-term effects of primary prevention and cardio-protective strategies? (3) Is primary prevention cost-effective or should society invest its resources elsewhere?
Advances in early detection and treatment of cancer has increased the population of cancer survivors, however cardiotoxicity of lifesaving cancer treatment can interfere with it?s planned completion and lead to sub-optimal cancer outcomes and increased downstream morbidity, cost and mortality. We propose to evaluate comparative & cost effectiveness of primary prevention and cardioprotective oncology regimen strategies on short-term and long-term cardiovascular, cancer and economic outcomes. Completion of the aims will guide healthcare policy on primary prevention and cardio-protective regimens, improve patient outcomes and identify subgroups who may benefit the most.
