Sex differences in risk of second malignant tumours after Hodgkin's disease in childhood.

There have been reports of a high incidence of second malignant disorders in survivors of Hodgkin's disease. We studied the cumulative incidence of second tumours in 191 children, who were 16 years or younger at diagnosis, with stage IA-IVB Hodgkin's disease, treated at the Joint Center for Radiation Therapy, Boston, between 1969 and 1988. The 10-year actuarial survival was 89 (SE 2)%. The median follow-up time was 11 (range 3-21) years from diagnosis. 109 children were initially treated with radiotherapy alone, 61 received chemotherapy and radiotherapy, and 21 received chemotherapy alone. Second tumours arose in 15 patients 6-20 years after the diagnosis of Hodgkin's disease. The estimated cumulative incidence of second malignant disorders at 15 years was 12 (4)% overall. 10 of the second tumours arose among 66 female patients, compared with 5 among 125 male patients (cumulative incidence 24 [9] vs 5 [3]%). The relative risk of a second tumour for female compared with male patients was 4.5 (95% CI 1.4-15.1; p = 0.013). For male patients, the observed incidence of second tumours was 18 times that expected for the normal population (95% CI 6-42), whereas for female patients it was 57 times that expected (27-105). 13 of the second malignant disorders were solid tumours, including 4 breast cancers. Thus, the risk of a child treated for Hodgkin's disease developing a second tumour is higher for girls than for boys. The cumulative incidence of second cancers increases from 10 years after treatment. These findings emphasise the importance of continued surveillance in patients treated for Hodgkin's disease.