Abstract
BACKGROUND: Improved survival rates in pediatric cancer have shifted focus to long-term effects of treatment, with cardiovascular complications emerging as a leading cause of morbidity and mortality. Understanding the patterns and predictors of cardiotoxicity is crucial for risk stratification, treatment optimization, and long-term care planning. OBJECTIVE: This study investigated the prevalence, incidence, and risk factors of cardiotoxicity in pediatric cancer survivors using data from the Childhood Cancer Survivor Study. METHODS: We conducted a retrospective cohort study of 24,938 five-year survivors of childhood cancer diagnosed between 1970 and 1999. Cardiovascular complications, including cardiomyopathy, coronary artery disease, valvular heart disease, and arrhythmias, were assessed through self-reported questionnaires and medical record review. Cox proportional hazards models were used to evaluate risk factors, and a prediction model was developed using multivariable logistic regression. RESULTS: The cumulative incidence of any cardiovascular complication by 30 years postdiagnosis was 18.7% (95% CI 17.9%-19.5%). Significant risk factors included anthracycline exposure (hazard ratio 2.31, 95% CI 2.09-2.55 for doses ≥250 mg/m²), chest radiation (hazard ratio 1.84, 95% CI 1.66-2.05 for doses ≥20 Gy), older age at diagnosis, male sex, and obesity. A risk prediction model demonstrated good discrimination (C statistic 0.78, 95% CI 0.76-0.80). Survivors had a significantly higher risk of cardiovascular complications compared with sibling controls (odds ratio 3.7, 95% CI 3.2-4.2). CONCLUSIONS: Childhood cancer survivors face a substantial and persistent risk of cardiovascular complications. The identified risk factors and prediction model can guide personalized follow-up strategies and interventions. These findings underscore the need for lifelong cardiovascular monitoring and care in this population.