New model predicts cardiomyopathy risk in childhood cancer survivors

Researchers have recently developed prediction models with highest-to-date performance to estimate the 10-year risk of cardiomyopathy in long-term survivors of childhood cancer.

Survivors from the St. Jude Lifetime Cohort (SJLIFE; model-development; n=3,479; median age 32.3 years) and the Childhood Cancer Survivor Study (CCSS; model-validation; n=6,875; median age 33.2 years) underwent assessment for demographics and cardiovascular risk factors, treatment exposures, and polygenic risk scores (PRSs) for cardiomyopathy, heart failure, cardiac structure and function, and anthracycline-related cardiomyopathy risk.

The researchers used multivariable Poisson regression to predict the 10-year risk of cardiomyopathy (Common Terminology Criteria for Adverse Events grade ≥3: requiring heart failure medications or heart transplantation or leading to death) following baseline visit/survey. They evaluated the performance of the model using area under the receiver operating characteristics curve (AUC).

Among childhood cancer survivors, 75 (2.2 percent, SJLIFE) had clinically identified cardiomyopathy, and 87 (1.3 percent, CCSS) had self-reported cases within 10 years of the baseline assessment. AUC of the clinical model with sex, age at cancer diagnosis, cumulative anthracycline, and mean heart radiation doses was 0.833 in SJLIFE and 0.812 in CCSS.

Age at baseline, hypertension, and genetic ancestry correlated with higher rates of cardiomyopathy in SJLIFE but did not increase AUC in CCSS (0.812). However, the addition of PRS for hypertrophic cardiomyopathy and left ventricular end-systolic volume enhanced AUC in CCSS (0.822; p=0.016).

“Compared with existing survivorship-care guidelines, the PRS model classified fewer survivors as high-risk or moderate-risk, while identifying survivors in those categories as having 1.5-times greater risk,” the researchers said.