Local radiation dose and solid second malignant neoplasms after childhood cancer in Germany: a nested case-control study.

Radiotherapy (RT) has been associated with the development of solid second malignant neoplasms (SMNs) in childhood cancer survivors. The aim of this study was to analyse the effect of cumulative doses of previous RT received at the SMN body region, at all other body regions and at body regions adjacent to the SMN, on the risk of developing a solid SMN. A total of 190 cases diagnosed with a solid second malignant neoplasm in 1980-2002 were matched with 368 controls with single neoplasm from the database of the German Childhood Cancer Registry (GCCR) (33,809 patients at cut-off date). The GCCR registers approximately 97 % of all childhood malignancies which occur at an age of less than 15 years in Germany since 1980. It was found that 147 (77.4 %) cases had received RT compared to 208 (56.6 %) controls with cumulative focus doses from 8 to 110 Gy. Fifty per cent of the SMNs and 60 % of RT affected the head region. RT was shown to increase the risk of a solid second tumour within the body region of radiation by 5.3 % per Gy (odds ratio 1.053; 95 % confidence interval 1.036-1.071). With increasing age at diagnosis and with more recent treatment eras, this effect decreased. Cumulative RT doses received at all other body regions or only at body regions adjacent to the SMN did not show an additional effect on the risk of developing an SMN. It is thus concluded that RT is the main risk factor for the development of SMNs within the irradiated body region. Late effects surveillance of former patients should give special attention to the originally irradiated parts of the body.