RADIATION-DOSE, CHEMOTHERAPY AND RISK OF OSTEOSARCOMA AFTER SOLID TUMORS DURING CHILDHOOD

Osteosarcoma is the most frequent second primary cancer occurring duri ng the first 20 years following treatment for a solid cancer in childh ood. Using a cohort study of children treated for a solid cancer, we i nvestigated the incidence and etiology of osteosarcoma as a second mal ignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiatio n and the risk of osteosarcoma, taking into account chemotherapy recei ved. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 19 42 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-co ntrol study, we matched 32 cases and 160 controls for sex, type of fir st cancer, age at first cancer and the duration of follow-up. Paramete rs studied were the incidence of osteosarcoma, the cumulative local do se of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linea r function of the local dose of radiation (excess relative risk per gr ay 1.8), and was found to increase with the number of moles of electro philic agents per square meter but not with other drugs. No interactio n was noted between radiotherapy and chemotherapy. Bilateral retinobla stoma, Ewing's sarcoma and soft tissue sarcoma were found to render pa tients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of pat ients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer tr eated with radiotherapy plus high doses of chemotherapy, without focus ing exclusively on the radiation field. (C) 1998 Wiley-Liss, Inc.