Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study.
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.
van der Pal
Helena J
HJ
Departments of Medical Oncology and Pediatric Oncology, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands. h.j.vanderpal@amc.uva.nl
van Dalen
Elvira C
EC
Hauptmann
Michael
M
Kok
Wouter E
WE
Caron
Huib N
HN
van den Bos
Cor
C
Oldenburger
Foppe
F
Koning
Caro C
CC
van Leeuwen
Flora E
FE
Kremer
Leontien C
LC
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004317:Doxorubicin / Q000009:adverse effects; D004452:Echocardiography; D015251:Epirubicin / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*
D018943:Anthracyclines; D015251:Epirubicin; D004317:Doxorubicin