RADIOTHERAPY, ALKYLATING-AGENTS, AND RISK OF BONE CANCER AFTER CHILDHOOD-CANCER

Background: Individuals who had cancer in childhood are at higher risk of developing bone cancer than any other type of second primary cance r. Purpose: Using the population-based National Registry of Childhood Tumours in Britain, we investigated the incidence and etiology of seco nd primary bone cancer after childhood cancer in a cohort study and in a case-control study. Methods: A cohort study of 13 175 3-year surviv ors of childhood cancer diagnosed in Britain between 1940 and 1983 rev ealed 55 subsequent bone cancers. A largely nested case-control study comprised 59 case subjects developing second primary bone cancer, and 220 control subjects were selected and matched for sex, type of first cancer, age at first cancer, and interval between diagnosis of first c ancer and subsequent bone cancer. Outcome measures were the incidence of bone cancer after childhood cancer, the cumulative dose of radiatio n received at the site of the second bone cancer in the case subject a nd at the corresponding anatomic site in the matched control subjects, and the cumulative dose of alkylating agents and vinca alkaloids rece ived by case and control subjects. Results: The percentage of 3-year s urvivors developing bone cancer within 20 years did not exceed 0.9%, e xcept following heritable retinoblastoma (7.2%), Ewing's sarcoma (5.4% ), and other malignant bone tumors (2.4%). The risk of bone cancer inc reased substantially with increased cumulative dose of radiation to th e bone (P<.001, linear trend). At the highest levels of exposure, howe ver, the risk appeared to decline somewhat (P = .065, nonlinearity). E xposure to less than 10 Gy was, at worst, associated with only a small increased relative risk (RR) of bone cancer (RR = 0.7; 95% confidence interval = 0.2-2.2). The risk of bone cancer increased linearly (P = .04, one-tailed test) with increased cumulative dose of alkylating age nts. Implications: This population-based study provides grounds for re assurance of the majority of survivors in that their risk of developin g bone cancer within 20 years of 3-year survival did not exceed 0.9%. The higher risks found for bone cancer following the other specific ra re types of childhood cancer provide a rational basis for surveillance . The RRs reported for bone cancer after specified levels of exposure to radiation should help in making decisions concerning future treatme nt protocols.