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Cardiac Function in 5-Year Survivors of Childhood CancerA Long-term Follow-up Study
Helena J. van der Pal, MD;
Elvira C. van Dalen, MD, PhD;
Michael Hauptmann, MSc, PhD;
Wouter E. Kok, MD, PhD;
Huib N. Caron, MD, PhD;
Cor van den Bos, MD, PhD;
Foppe Oldenburger, MD, PhD;
Caro C. Koning, MD, PhD;
Flora E. van Leeuwen, MSc, PhD;
Leontien C. Kremer, MD, PhD
Arch Intern Med. 2010;170(14):1247-1255. doi:10.1001/archinternmed.2010.233
Background 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.
Methods 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.
Results 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.
Conclusions 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.
Author Affiliations: Departments of Medical Oncology (Dr van der Pal), Pediatric Oncology (Drs van der Pal, van Dalen, Caron, van den Bos, and Kremer), Cardiology (Dr Kok), and Radiation Oncology (Drs Oldenburger and Koning), Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands; and Departments of Bioinformatics and Statistics (Dr Hauptmann) and Epidemiology (Dr van Leeuwen), Netherlands Cancer Institute, Amsterdam.
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