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Second Malignant Neoplasms After Treatment for Hodgkin’s Disease in Childhood or Adolescence

From the Departments of Pediatrics, Cancer Prevention, Epidemiology and Biostatistics, Pathology, Radiation Medicine, and Psychology, Roswell Park Cancer Institute; Departments of Pediatrics and Social and Preventive Medicine, School of Medicine and Biomedical Sciences, and Department of Natural Sciences, Roswell Park Graduate Division, University at Buffalo, State University of New York, Buffalo, NY.

Address reprint requests to Daniel M. Green, MD, Department of Pediatrics, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263; email daniel.green{at}roswellpark.org

PURPOSE: To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin’s disease diagnosed in children and adolescents.

PATIENTS AND METHODS: One hundred eighty-two consecutive, previously untreated patients with Hodgkin’s disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence.

RESULTS: Twenty-eight patients developed an SMN at a mean of 14.93 ± 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin’s disease. The cumulative percentage of patients who developed an SMN was 26.27 ± 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin’s lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results.

CONCLUSION: Successfully treated children and adolescents with Hodgkin’s disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.

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