Melanoma Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PURPOSE Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood. METHODS We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model. RESULTS Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m² (HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]). CONCLUSION Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.