Childhood Cancer Survivors at Double the Risk of Melanoma: Study Highlights Key Risk Factors

While the absolute risk of melanoma by age 40 remained low, survivors of childhood cancer exhibited a standardized incidence ratio of 2.0 for invasive skin or ocular melanoma compared to the general population. This elevated risk was largely attributed to prior exposure to radiation therapy and certain types of cytotoxic chemotherapy.

Melanoma has been identified as a subsequent malignant neoplasm in childhood cancer survivors, but its risk factors and long-term survival outcomes remain poorly understood. For this purpose, Seth J. Rotz, Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation, Cleveland Clinic Children's Hospital, Cleveland, OH, and colleagues aimed to investigate melanoma in adult survivors of childhood cancer.

For this purpose, the researchers assessed the incidence, risk factors, and outcomes of melanoma among participants in the Childhood Cancer Survivor Study cohort. They calculated cumulative incidence and standardized incidence ratios (SIRs) and employed multivariable Cox models to determine hazard ratios (HRs) for melanoma risk factors. The analysis integrated radiation exposure across seven body regions and melanoma status for eight regions per survivor into the Cox model.

The researchers analyzed data from 25,716 participants in the Childhood Cancer Survivor Study. The findings include:

• 177 melanomas were identified in 160 survivors (110 invasive, 62 in situ cutaneous, and five ocular).
• The 40-year melanoma cumulative incidence was 1.1% for all participants and 1.5% for those exposed to a cumulative radiation dose of ≥40 Gy.
• Compared with the general population, the standardized incidence ratio (SIR) for invasive skin or ocular melanoma was 2.0.
• Risk factors for increased cutaneous melanoma included:
  • A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0).
  • A cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m² (HR, 1.9).
  • Bleomycin exposure (HR, 2.2).
• Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4).

"The findings revealed that childhood cancer survivors have over twice the risk of developing melanoma compared to the general population, with invasive melanoma significantly increasing the risk of death. High-dose radiation, exposure to alkylating agents, and bleomycin were identified as key risk factors, underscoring the need to incorporate these factors into future patient guidance and screening strategies," the researchers concluded.

Reference:

Seth J. Rotz et al., Melanoma Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. JCO 0, JCO-24-01519. DOI:10.1200/JCO-24-01519