CANCER INCIDENCE AFTER RETINOBLASTOMA - RADIATION-DOSE AND SARCOMA RISK

Context.-There is a substantial risk of a second cancer for persons wi th hereditary retinoblastoma, which is enhanced by radiotherapy. Objec tive.-To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sar coma development. Design.-Cohort incidence study of patients with reti noblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tiss ue sarcomas. Setting/Participants.-A total of 1604 patients with retin oblastoma who survived at least 1 year after diagnosis, identified fro m hospital records in Massachusetts and New York during 1914 to 1984. Results.-Incidence of subsequent cancers was statistically significant ly elevated only in the 961 patients with hereditary retinoblastoma, i n whom 190 cancers were diagnosed, vs 6.3 expected in the general popu lation (relative risk [RR], 30 [95% confidence interval, 26-47]), Cumu lative incidence (+/-SE) of a second cancer at 50 years after diagnosi s was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0% ) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histol ogic types occurred in patients with hereditary retinoblastoma. For so ft tissue sarcomas, the RRs showed a stepwise increase at all dose cat egories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at do ses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.0 5). Conclusions.-Genetic predisposition has a substantial impact on ri sk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationsh ip is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether thei r extraordinary cancer risk extends to common cancers of adulthood.