Cardiac Function in 5-Year Survivors of Childhood Cancer

Abstract

Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. We evaluated the prevalence and determinants of left ventricular (LV) dysfunction in a large cohort of long-term CCSs treated with different potentially cardiotoxic therapies. The study cohort consisted of all adult 5-year CCSs who were treated with potentially cardiotoxic therapies and who visited our late effects outpatient clinic. Echocardiography was performed in patients who had received anthracyclines, cardiac irradiation, high-dose cyclophosphamide, or high-dose ifosfamide. Detailed treatment data were registered. Both multivariate linear and logistic regression analyses were performed. Of 601 eligible CCSs, 525 (87%) had an echocardiogram performed, of which 514 were evaluable for assessment of the LV shortening fraction (LVSF). The median overall LVSF in the whole group of CCSs was 33.1% (range, 13.0%-56.0%). Subclinical cardiac dysfunction (LVSF <30%) was identified in 139 patients (27%). In a multivariate linear regression model, LVSF was reduced with younger age at diagnosis, higher cumulative anthracycline dose, and radiation to the thorax. High-dose cyclophosphamide and ifosfamide were not associated with a reduction of LVSF. Vincristine sulfate was associated with a nonsignificant decrease of cardiac function (P = .07). Epirubicin hydrochloride was as cardiotoxic as doxorubicin when corrected for tumor efficacy, and daunorubicin hydrochloride seemed less cardiotoxic. A high percentage (27%) of young adult CCSs have an abnormal cardiac function. The strongest predictors of subclinical cardiac dysfunction are anthracycline dose, cardiac irradiation, and younger age at diagnosis. There is a suggestion that daunorubicin is less cardiotoxic than other anthracyclines.