Two-fold increased risk of melanoma in childhood cancer survivors

Abstract

Childhood cancer survivors have a 2-fold increased risk of melanoma in comparison with the general population, with a 2-fold increased risk of death for those with invasive melanoma, according to the largest and most comprehensive study to date on melanoma in childhood cancer survivors.¹

“We have known for some time that childhood cancer survivors are at higher risk for melanoma compared to the general population, but to date have not been able to tease out the relevant risk factors for melanoma,” says the lead author of the study, Seth J. Rotz, MD, a pediatric hematologist/oncologist at the Cleveland Clinic in Ohio.

Previous studies have suggested a potential relationship between the therapeutic dose of radiation and melanoma, he adds, but the data are limited by the lack of large enough patient populations with granular data available.

To overcome these limitations, Dr Rotz and his colleagues used a large data set from the Childhood Cancer Survivor Study that included 25,716 participants. With a median follow-up of 26 years (range, 5–69 years), 160 survivors developed 177 melanomas. One hundred ten of these melanomas were invasive, 62 were in situ, and 5 were ocular.

In comparison with the expected risk of melanoma in the general population, survivors had a more than 2-fold increased risk of invasive skin and ocular melanoma, with no significant differences found after adjustments for the attained age of the survivor. Survivors had a more than 2-fold increased risk of death if they developed invasive melanoma at any site.

To examine treatment factors associated with the increased risk of melanoma, the researchers looked at two radiation measures: the maximum target dose received by any of the seven body regions evaluated (i.e., leg, arm, chest, abdomen, pelvis, neck, and head/brain) and the maximum target dose to various combinations of these seven radiation body regions mapped to areas of interest for melanoma. They also looked at cumulative exposures to chemotherapeutic drugs.

For radiation, the study is the first to find a dose-dependent relationship between radiation therapy and melanoma in childhood cancer survivors, with high-dose radiation exposure linked to melanoma. Survivors were at a significantly higher risk of developing melanoma if they received a cumulative radiation dose of ≥40 Gy. In comparison with the general population, the standardized incidence ratio for invasive skin or ocular melanoma was 2.0 (95% confidence interval [CI], 1.6–2.4).

The study also clarified the risk of exposure to specific types of chemotherapy and showed an increased risk of cutaneous melanoma in survivors treated with a cumulative cyclophosphamide equivalent dose of >20,000 mg/m² (hazard ratio [HR], 1.9; 95% CI, 1.1–3.6) or exposure to bleomycin (HR, 2.2; 95% CI, 1.2–4.1).

“Now that we know the risk factors, we should be able to clinically understand which patients are at higher risk,” says Dr Rotz. “We need to determine if specific screening approaches, such as an annual dermatologist skin exam, can help detect melanoma sooner in these patients and if that ultimately can prevent advanced melanoma disease or even death.”