Risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy: meta-analysis of nine epidemiological studies

Abstract

In the light of notable advances made in childhood cancer therapies, an understanding of the late effects of treatment is important for continued medical care. We conducted a meta-analysis of studies on the excess relative risk (ERR) of second malignant neoplasm (SMN) among childhood cancer survivors treated with radiotherapy. Relevant studies were retrieved by searching the PubMed database, supplemented by hand-searching of reference lists of already retrieved papers. Nine studies were identified and overall ERR estimates were calculated using a fixed effects model and a random effects model. The overall ERR per Gy (absorbed dose of ionising radiation) estimates of radiotherapy by a fixed effect model and a random effects model were 0.50 [95% CI 0.20, 1.21] and 0.53 [95% CI 0.22, 1.31] respectively. Heterogeneity among studies was suggested by Cochran's Q statistic (Q = 40.4, d.f. = 8, P < 0.001). The estimate obtained using a random effects model was far smaller than the corresponding estimate of 1.7 [95% CI 1.1, 2.5] from the study on atomic bomb survivors exposed as young children, suggesting underestimation of ERR estimates among the nine studies compared with the estimates from the study of atomic bomb survivors. In view of the heterogeneity and underestimation in ERR estimates, more studies concerning the risk of SMN among childhood cancer survivors are still needed for further understanding of the carcinogenic effects of radiotherapy on children.