Cardiotoxicity in Pediatric Cancer Survivorship: Patterns, Predictors, and Implications for Long-term Care

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 aimed to investigate the prevalence, incidence, and risk factors of cardiotoxicity in pediatric cancer survivors using data from the Childhood Cancer Survivor Study (CCSS). 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 post-diagnosis was 18.7% (95% CI: 17.9%-19.5%). Significant risk factors included anthracycline exposure (HR 2.31, 95% CI: 2.09-2.55 for doses ≥250 mg/m 2 ), chest radiation (HR 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 to sibling controls (OR 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.