Risk Models Predict Childhood Cancer Survivors’ Long-Term Cardiovascular Risks

Combined analysis of established risk factors predicts long-term cardiovascular complications among childhood cancer survivors more accurately than single-factor risk assessments, according to data from the Childhood Cancer Survivor Study (CCSS), published in the Journal of Clinical Oncology.

“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,” wrote Eric J. Chow, MD, MPH, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues. “These models also provide a stronger evidence base upon which to develop and test potential screening and intervention strategies for high-risk patients, including assessing the cost effectiveness of various surveillance strategies.”

Childhood cancer survivors have at least a 10-fold increased risk of stroke and ischemic heart disease, on average, compared with their siblings.

“However, these averages mask significant variation, with some groups experiencing cumulative incidences ≥ 10% of having one of these events by middle age and other groups having incidences not dissimilar to those of siblings without a history of childhood cancer (< 2%),” the authors noted.

The researchers analyzed associations between long-term ischemic heart disease and stroke incidence with single risk factors and combined risk scores from multivariate CCSS models among 13,060 5-year survivors of diverse childhood cancers and 4,023 siblings. The authors then tested the CCSS models with data from two external validation cohorts: the St. Jude Lifetime Cohort Study and the Emma Children’s Hospital cohort (n = 1,842 and 1,362, respectively). At a median follow-up of 19 years (0 to 34 years), ischemic heart disease and stroke had been reported in 265 and 295 study participants, respectively, by age 50 years.

Risk factors included in the CCSS models included sex; age at diagnosis (in 5-year increments); chemotherapy exposures; and head, neck, and chest radiotherapy exposures. The researchers used resulting risk model outputs to identify statistically distinct low-, medium-, and high-risk categories. Rate ratios were compared with patients’ siblings.  

“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 authors reported.

Using the CCSS models can inform patient counseling discussions about modifiable cardiovascular risk factors after treatment and other survivorship issues.