Children and adolescents diagnosed with cancer now have on average >80% 5-year survival. However, premature cardiovascular (CV) disease has become the leading non-cancer cause of late mortality among childhood cancer survivors. Our existing work has shown that traditional CV risk factors such as hypertension, dyslipidemia, insulin resistance/diabetes remain very important, by increasing (in synergistic fashion) the risk of major CV events such as ischemic heart disease and heart failure. However, the existing research has been limited by misclassification of CV risk factor status (i.e., when defined by self-report or medication usage alone), including issues with both underdiagnosis (i.e., people with these risk factors present but who are unaware) and uncertainty of disease control (i.e., potential undertreatment). This proposal will utilize the largest, best characterized childhood cancer survivor cohort in the world, the Childhood Cancer Survivor Study (CCSS; n=24,466), a NCI-funded resource. We will use CCSS-derived validated risk prediction algorithms to select survivors at high risk of serious heart disease (n=800) based on past cancer treatment exposures. Among these 800 survivors, we propose to determine the magnitude of underdiagnosis and undertreatment of hypertension, dyslipidemia, and diabetes via in-person (home-based) measurements supplemented by medical record review. We predict that around 60% of survivors (n~480) will be underdiagnosed or undertreated with respect to one of these three CV risk factors. Survivors who are underdiagnosed or undertreated will then be eligible to participate in a 1-year long randomized controlled trial, where we will measure the efficacy of an Institute of Medicine (IOM) recommended personalized survivorship care plan (SCP) emphasizing CV risk, supplemented by a remotely delivered clinician-led self-management counseling intervention, to improve control of these three CV risk factors (i.e., reduce rates of undertreated hypertension, dyslipidemia, and diabetes). Survivors randomized to the control arm can receive the intervention on a delayed basis. Finally, our proposal seeks to better understand barriers among survivors and their primary healthcare providers that contribute to CV risk factor undertreatment. Knowledge derived from this study will improve the assessment and treatment of important CV risk factors in this high risk population. The proposed intervention, if successful, will be disseminable and low cost, and will have the potential to improve health and reduce mortality in these younger adults who live the majority of their lives as cancer survivors at increased risk of serious CV disease.

Public Health Relevance

Improved treatments have resulted in the vast majority of children diagnosed with cancer to be cured of their disease. However, premature cardiovascular disease has now become the leading non-cancer cause of death among childhood cancer survivors. The proposed project seeks to: 1) better describe the burden of important cardiovascular conditions like high blood pressure, abnormal cholesterol/lipid levels, and diabetes among long- term childhood cancer survivors; 2) determine if control of these conditions can be improved by providing survivors and their primary healthcare providers with additional tailored education and counseling; 3) identify barriers to successful control of these conditions among survivors and their healthcare providers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Cancer, Heart, and Sleep Epidemiology A Study Section (CHSA)
Program Officer
Prabhudas, Irene
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Fred Hutchinson Cancer Research Center
Research Institutes
United States
Zip Code
Chow, Eric J; Antal, Zoltan; Constine, Louis S et al. (2018) New Agents, Emerging Late Effects, and the Development of Precision Survivorship. J Clin Oncol 36:2231-2240
Chow, Eric J; Chen, Yan; Hudson, Melissa M et al. (2018) Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer. J Clin Oncol 36:44-52
Armenian, Saro H; Yang, Dongyun; Teh, Jennifer Berano et al. (2018) Prediction of cardiovascular disease among hematopoietic cell transplantation survivors. Blood Adv 2:1756-1764