New modeling addresses heart disease in childhood cancer survivors

Researchers say they are making headway toward developing predictive models that could help guide clinicians on counseling and preventive measures against heart disease and stroke in survivors of childhood cancer.

In a study published in the Journal of Clinical Oncology,¹ researchers evaluated more than 13,000 participants in the Childhood Cancer Survivor Study (CCSS), and developed models that compared the incidence of ischemic heart disease and stroke in this group against their siblings who had not received cancer treatment.

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Eric J. Chow, MD, MPH, of the Fred Hutchinson Cancer Research Center, Seattle, Washington, led the study, and says his research demonstrates that validated prediction models now exist to provide individualized risk assessments for heart disease and stroke in childhood cancer survivors.

“These can be used for counseling and to help clinicians determine the utility of adopting prevention measures,” Chow says.

Risks after childhood cancer

There are nearly a half-million childhood cancer survivors in the United States, according to the new report, and cardiovascular disease is the top noncancer contributor to early disease and death in this group.

Research has uncovered a 10-fold increase in the risk of ischemic heart disease and stroke in childhood cancer survivors when compared against their siblings, according to the investigators, but there is also a high level of variation based on what type of treatments and exposures survivors had as well as lifestyle and genetic factors.

Predictors of cardiovascular disease play a big role in clinical decision making as people age, the report notes, and the increased incidence of heart disease and stroke observed in this population highlights the need to begin screening and intervention at an earlier age.

The risk models developed for the study aimed to predict the incidence of ischemic heart disease and stroke in 5-year childhood cancer survivors. In the population studied, 35.1% of the cohort had cranial radiotherapy and 25.9% received chest radiotherapy. Researchers found that after a nearly 20-year follow-up, 7.5% of the individuals enrolled in the childhood cancer study developed ischemic heart disease by age 50 years and 6.3% had a stroke, compared with a 1.2% incidence of heart disease in siblings of cancer survivors and a 1.1% incidence of stroke. The study notes that when typical cardiovascular risks such as smoking and hypertension were assessed in the childhood cancer cohort, they were “generally uncommon.” Further modeling of the childhood cancer cohort, however, identified a set of predictors at the 5-year cancer survival point that could be used to develop a risk score. Risk scores were based on gender, chemotherapy and radiation exposures, and were used to develop low-, moderate-, and high-risk groups.

“The cumulative incidences at age 50 years among CCSS low-risk groups were <5%, compared with approximately 20% for high-risk groups (P <.001); cumulative incidence was only 1% for siblings (P <.001 vs low-risk survivors),” the researchers write. “Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.”

Models can predict, not prevent

As far as specific preventive measures, however, Chow says his study didn’t go that far.

“Our study was focused on developing prediction measures and not prevention measures,” Chow says. “But control of conventional heart disease/stroke risk factors such as hypertension, diabetes, dyslipidemia should be emphasized, plus lifestyle factors known to influence the risk of these conditions.”

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Some factors that also increase disease risk factors in childhood cancer survivors include the toxicity of the treatments they receive, Chow says. For example, radiation to the brain can increase the risk of stroke, and chest radiation and increase the risk of ischemic heart disease.

Chow says he hopes his study raises awareness among primary care physicians and cardiologists that survivors of childhood cancer, specifically by young adulthood, would benefit from counseling and screening for key conditions such as heart disease and stroke.

REFERENCE

1.    Chow EJ, Chen Y, Hudson MM, et al. Prediction of ischemic heart disease and stroke in survivors of childhood cancer. J Clin Oncol. 2018;36(1):44-52.