Lessons from the hearts of survivors of childhood cancer

With growing numbers of childhood cancer survivors, it becomes increasingly important to understand the long-term toxicities associated with cure from malignancy. Many survivors were exposed to cardiotoxic chemotherapeutic agents at young ages. Indeed, cardiotoxicity is a leading cause of treatment-related morbidity and mortality in survivors of childhood cancer, and anthracycline exposure is a leading cause of these late cardiac effects. Nonetheless, anthracyclines remain critical agents in treating many pediatric cancers. Strategies to prevent anthracycline-associated cardiotoxicity include limiting lifetime cumulative anthracycline doses and adding cardioprotectant agents, such as dexrazoxane, to anthracycline-based regimens. However, attempts to reduce the cardiotoxicity of anthracyclines must also consider their effect on anti-cancer efficacy as well as new potential toxicities. In survivors of childhood acute lymphoblastic leukemia, the data suggest that including dexrazoxane in anthracycline-based regimens can prevent heart damage, does not reduce anti-leukemic efficacy, and can be safely administered. The controversies associated with dexrazoxane exemplify the challenges of changing therapy in cancers with a relatively good chance of event-free survival in efforts to prevent long-term sequelae. Studies of very-long-term survivor cohorts will continue to inform current practices. Continued efforts are needed to minimize cardiotoxic exposures during cancer treatment, to deliver safe and effective cardioprotectant measures when cardiotoxic agents cannot be avoided, to identify patients at greatest risk of serious cardiac toxicity, and to educate providers in the optimal care of survivors.