Risk Stratification for Cardiotoxicity in Childhood Cancer Survivors: State-of-the-Art Review and a Novel Two-Step Approach

Numerous studies and international recommendations have investigated risk factors that put childhood cancer survivors (CCSs) at a higher risk of late-onset cancer therapy-related cardiovascular toxicities (CTR-CVTs). While anthracyclines and chest-directed radiotherapy are well-established high-risk treatments, other anticancer therapies, including alkylating agents, antimetabolites, targeted therapies, and hematopoietic stem cell transplantation, also carry potential cardiotoxic effects. The likelihood of developing CTR-CVT is further modulated by the presence of cardiometabolic risk factors, prior occurrence of CTR-CVT during treatment, and certain clinical conditions, which may predispose survivors to long-term cardiovascular complications. This state-of-the-art review summarizes current strategies for stratifying the risk for developing CTR-CVT in CCSs. We then propose a tailored, multimodal approach for guiding cardio-oncological assessments both during treatment and in long-term follow-up, including a structured echocardiographic protocol. Future perspectives include validation of this approach to optimize early detection and personalized management of CTR-CVT.