CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.
Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.
Dr. Alberto Pappo
"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."
Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).
The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.
In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.
The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.
Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).
The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.
Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.
Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."
Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.
Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.
"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.
The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.