Risk of morbidity and mortality from cardiovascular disease following radiotherapy for childhood cancer: A systematic review

Purpose: To evaluate the existing evidence regarding the long-term risk of cardiovascular disease (CVD) after radiotherapy for childhood cancer. Patients and methods: MEDLINE and EMBASE were searched for articles reporting on radiation-induced CVD after childhood cancer published between 1966 and October 2002. Information about study design, population, treatment, outcome and risk factors were abstracted and the quality of each study was assessed. Results: Fourteen articles met all the eligibility criteria. Ten studies evaluated clinical cardiovascular events (CVE) and 11 cardiovascular mortality (CVM) after cardiac irradiation for childhood cancer. Four studies, all in survivors of Hodgkin's disease, showed a significantly increased standardised mortality ratio; a 22- to 68-fold increase compared to the general population. No study compared the risk of CVE with the general population. Three studies examined the risk of CVD (both CVM and CVE) after radiotherapy compared to an unexposed control group, and two showed a significantly increased relative risk. Many studies had important methodological limitations, related to completeness of follow-up, adjustment for other risk factors and outcome assessment in CVE studies. Conclusions: This systematic review demonstrates that the risk of CVM after cardiac irradiation for childhood cancer is increased compared to the general population and to unexposed patients. The risk of developing clinical CVE and the precise risk factors for developing CVE or CVM after radiotherapy remain unclear. New welldesigned studies are needed to reliably evaluate the long-term risk of CVD following radiotherapy and associated risk factors.