Second primary tumors in hereditary retinoblastoma: A register-based study, 1945-1997 - Is there an age effect on radiation-related risk?

Objective: The aim of this study is to evaluate the influence of age at ext ernal beam irradiation (EBRT) on the occurrence of second primary tumors (S PTs) inside and outside the irradiation field in hereditary retinoblastoma patients. Design: Cross-sectional study. Participants: The study included 263 hereditary retinoblastoma patients bor n in The Netherlands between 1945 and 1997. Methods: A national register-based follow-up cohort study was performed on hereditary retinoblastoma patients. information on therapy, age at irradiat ion, and location of SPT was obtained from the register. The Kaplan-Meier m ethod calculated cumulative incidences of SPT in three subgroups: irradiati on before (early EBRT) and after 12 months of age (late EBRT), and no irrad iation, The Mantel-Cox method determined the statistical significance of di fferences between the cumulative incidence curves. Main Outcome Measures: Development of SPT inside and outside a precisely de fined irradiation field in relation to age at irradiation. Our definition e xcluded pineoblastoma as SPT, because they constitute part of a trilateral retinoblastoma; in addition, they lie outside the field of irradiation. Results: The cumulative incidence of SPT at the age of 25 years was 22% (95 % confidence intervals 13%-34%) in the early EBRT group, 3% (0%-14%) in the late EBRT group, and 5% (1%-16%) in the nonirradiated group (Mantel-Cox ov erall: P = 0.001; between early and late EBRT, P = 0.04). However, in early irradiated patients, the incidence of SPTs inside and outside the irradiat ion field was similar (11%), and the difference between early and late EBRT in incidence of SPT inside the field of irradiation was less prominent tha n overall (11% vs. 3%: P = 0.37). Sensitivity analysis showed the results d epended on the way SPT, irradiation field, and, especially, pineoblastomas are defined. Conclusions: Hereditary retinoblastoma confers an increased risk for the de velopment of SPT, especially in patients treated with EBRT before the age o f 12 months, However, the presence of similar numbers of SPTs inside and ou tside the irradiation field suggests that irradiation is not the cause. In other words, this study does not show an age effect on radiation-related ri sk. Rather, early EBRT is probably a marker for other risk factors of SPT. Ophthalmology 2001; 108: 1109-1114 (C) 2001 by the American Academy of Opht halmology.