Risk, risk factors and surveillance of subsequent malignant neoplasms in childhood cancer survivors: a review

Subsequent malignant neoplasms (SMNs) in childhood cancer survivors cause substantial morbidity and mortality. This review summarizes recent literature on SMN epidemiology, risk factors, surveillance, and interventions. Childhood cancer survivors experience long-term increased SMN risk compared to the general population, with more than 2-fold increased solid tumor risk extending beyond age 40 years. There is a dose-dependent increased risk for solid tumors following radiotherapy, with the highest risks for tumors occurring in or near the treatment field (e.g., >5-fold increased risk for breast, brain, thyroid, skin, bone, and soft-tissue malignancies). Alkylating and anthracycline chemotherapy increase the risk of several solid malignancies in addition to acute leukemia/myelodysplasia and these risks may be modified by other patient characteristics, such as age at exposure and, potentially, inherited genetic susceptibility. Strategies for identifying survivors at risk and initiating long-term surveillance have improved and interventions are underway to improve knowledge about late-treatment effects among survivors and caregivers. Better understanding of treatment-related risk factors and genetic susceptibility holds promise for refining surveillance strategies, and ultimately upfront cancer therapies.