Risk, Risk Factors, and Surveillance of Subsequent Malignant Neoplasms in Survivors of Childhood Cancer: A Review

Abstract

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. Survivors of childhood cancer experience long-term increased SMN risk compared with the general population, with a greater than twofold increased solid tumor risk extending beyond age 40 years. There is a dose-dependent increased risk for solid tumors after radiotherapy, with the highest risks for tumors occurring in or near the treatment field (eg, greater than fivefold increased risk for breast, brain, thyroid, skin, bone, and soft tissue malignancies). Alkylating and anthracycline chemotherapies increase the risk for development 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.

Fig 1.

Standardized incidence ratios and absolute excess risk of subsequent malignant neoplasm by attained age in international cohorts of survivors of childhood cancer.

Fig 2.

Fitted radiation dose response by type of second cancer, on the basis of previously published reports from the Childhood Cancer Survivor Study. Reprinted with permission.

Fig 3.

Relative risks and 95% CIs for categories of radiation dose and fitted dose-response models for four original studies and for all data combined (pooled analysis) for subsequent thyroid cancer. Category-specific relative risks for the LESG and CCSS-Nordic Studies were adjusted using the fitted linear-exponential (linear) model to reflect a referent of zero dose. CCSS, Childhood Cancer Survivor Study; Fr/UK, France and United Kingdom; LESG, Late Effects Study Group. Reprinted with permission.

Fig 4.

Breast cancer risk by radiation dose to the breast and ovary. Reprinted with permission.