A longitudinal study of anthracycline cardiotoxicity in pediatric Ewing sarcoma.

Abstract

9529 Background: Trends in cardiac function over time have not been previously described in Ewing sarcoma. Our cohort is unique as all the cardiac evaluations occurred systematically in one tertiary cardiology unit during a 28 year period. Objectives: 1.To evaluate the cardiac functional trends in the cohort at baseline, during treatment and in surveillance. 2.To evaluate the risk factors associated with cardiac toxicity. Design: Received ethics approval for a retrospective chart review of all patients less than 17 years, diagnosed with Ewing sarcoma from 1978-2006, treated initially at British Columbia Children’s Hospital . Methods: There was complete data on 71/79 eligible patients. Echocardiograms were recorded at 5 time points: pre treatment, worst function during treatment, on therapy completion, worst function during surveillance and the most recent echocardiogram. Cardiac toxicity was graded using CTCAE v 4.0. The statistical analysis with SAS software v 9.2 calculated the chi square and odds ratios to explore a possible association between exposure and outcome. Results: Median age at diagnosis 11.1 yrs (2.2-16.1 yrs), 52% female, metastatic in 17, overall survival 74% at 10yrs. A total of 397 echocardiograms were performed with 244 (61%) being normal and 153 (39%) being abnormal. The median cumulative dose of anthracyclines was 365mg/m2. Grade 1-5 cardiomyopathy occurred in 42 (59%) patients. Grade 3-5 toxicity occurred in 11 (15%) patients on chemotherapy completion increasing to 23 (32%) 120 months post diagnosis. The median time to the worst cardiac function was 51months (2-183). Four of 19 (20%) deaths were cardiac related including 2/3 cardiac transplants. Conclusions: Symptomatic cardiac toxicity increased from 20% noted in our earlier Ewings cohort (Kakader et al. 1997) to 32% with longitudinal evaluation assessments. Significant and progressive cardiac toxicity occurred after completion of chemotherapy.