Refining the 10-Year Prediction of Left Ventricular Systolic Dysfunction in Long-Term Survivors of Childhood Cancer

Abstract Background In childhood cancer survivors (CCS) at risk for heart failure, echocardiographic surveillance recommendations are currently based on anthracyclines and chest-directed radiotherapy dose. Whether the ejection fraction (EF) measured at an initial surveillance echocardiogram can refine these recommendations is unknown. Objectives The purpose of this study was to assess the added predictive value of EF at >5 years after cancer diagnosis to anthracyclines and chest-directed radiotherapy dose in CCS, for the development of left ventricular dysfunction with an ejection fraction  Methods Echocardiographic surveillance was performed in 299 CCS from the Emma Children’s Hospital in the Netherlands. Cox regression models were built including cardiotoxic cancer treatment exposures with and without EF to estimate the probability of LVD40 at 10-year follow-up. Calibration, discrimination, and reclassification were assessed. Results were externally validated in 218 CCS. Results Cumulative incidences of LVD40 at 10-year follow-up were 3.7% and 3.6% in the derivation and validation cohort, respectively. The addition of EF resulted in an integrated area under the curve increase from 0.74 to 0.87 in the derivation cohort and from 0.72 to 0.86 in the validation cohort (likelihood ratio p  Conclusions In CCS, an initial surveillance EF, in addition to anthracyclines and chest-directed radiotherapy dose, improves the 10-year prediction for LVD40. Through this strategy, both the identification of low-risk survivors in whom the surveillance frequency may be reduced and a group of survivors at increased risk of LVD40 could be identified.