We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.

Summary Cancer risks were studied in 834 thyroid cancer patients given 'l'I (4,551 MBq, average) Iodine-131 was first described in medical practice more than 40 years ago and is still frequently used in the diagnosis and treatment of thyroid disorders (Hamilton & Lawrence, 1942;Hertz & Roberts, 1942).In cases of nuclear explosions or reactor accidents large amounts of 131I could be spread over vast areas causing a potential hazard to human beings (Becker, 1987). Data on risks associated with radioactive iodines are still relatively scarce despite studies of populations exposed to fallout from nuclear weapons testing (Conard, 1984;Hamilton et al., 1987) and patients receiving diagnostic (Holm et al., 1989) and therapeutic doses of '"'I (Brincker et al., 1973;Edmonds & Smith, 1986;Hoffman, 1984;Holm, 1984;Saenger et al., 1968).Studies of thyroid cancer patients treated with '3'I are also rare, probably because of the low incidence of the disease and the associated small number of patients admitted to each centre. High-dose '"'I has been linked to leukaemia following treatment for thyroid cancer (Brincker et al., 1973;Edmonds & Smith, 1986) and also to cancers of the bladder (Edmonds & Smith, 1986). Record-linkage studies of patients with thyroid cancer have reported increased risks of leukaemia (Teppo et al., 1985), cancer of the breast, kidney and connective tissue (Tucker et al., 1985), and cancer of the nervous tissue and non-Hodgkin's lymphoma (0sterlind et al., 1985).The present study was designed to evaluate the risk of second primary cancer in a cohort of thyroid cancer patients treated with 13'I, and to contrast the risk with that of nonexposed thyroid cancer patients. Subjects and methodsPatient data were obtained from the oncologic centres of six university hospitals in Sweden: (1) Lund; (2) Malm6; (3) Gothenburg; (4) Stockholm; (5) Uppsala, and (6)

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