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Journal Article
Research Support, U.S. Gov't, P.H.S.
Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk.
JAMA 1997 October 16
CONTEXT: There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy.
OBJECTIVE: To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.
DESIGN: Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas.
SETTING/PARTICIPANTS: A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984.
RESULTS: Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, 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 doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05).
CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship 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 their extraordinary cancer risk extends to common cancers of adulthood.
OBJECTIVE: To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.
DESIGN: Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas.
SETTING/PARTICIPANTS: A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984.
RESULTS: Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, 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 doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05).
CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship 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 their extraordinary cancer risk extends to common cancers of adulthood.
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