Second cancers following pediatric Hodgkin's disease.

Abstract

To define the magnitude of second cancer risk among pediatric Hodgkin's disease survivors and to determine which factors influence this risk. At Stanford,694 children and teenagers were monitored for 1 to 31.6 years (mean, 13.1) after treatment for Hodgkin's disease. Relative risks (RRs), actuarial risks, and absolute excess risks for second malignancies were calculated. The influences of sex, age, stage, splenectomy, treatment and relapse were assessed by multivariate analysis. Fifty-six patients developed 59 secondary malignancies: 48 solid tumors, eight leukemias, and three non-Hodgkin's lymphomas. The RR of developing a second cancer was 15.4 (95% confidence interval [CI], 10.6 to 21.5) for females and 10.6 (95% CI, 6.6 to 16.0) for males. Breast cancer (n = 16) and sarcoma (n = 13) were the most common solid tumors. The actuarial risk at 20 years follow-up evaluation was 9.7% for males, 16.8% for females, and 9.2% for breast cancer. The median interval to diagnosis of a second malignancy was shortest for leukemia, 4.3 years, and longest for lung cancer, 18.4 years. Relapse of Hodgkin's disease increased the risk of second malignancy (hazards ratio [HR] = 2.6, P < .001). Hodgkin's disease stage, patient age, splenectomy, and treatment modality did not appear to alter overall risk, although chemotherapy was associated with subsequent leukemia. Aggressive Hodgkin's disease therapy is successful, but patients have a significant risk of second malignancy. Newer treatment programs focus on obtaining a relapse-free cure of Hodgkin's disease with judicious use of radiation and alkylating agent chemotherapy. Survivors of pediatric Hodgkin's disease require lifelong evaluation and cancer screening.