Abstract 10262: Cranial Irradiation: A Novel Risk Factor For Anthracycline Cardiotoxicity in Childhood Cancer Survivors
Introduction: Anthracycline-treated childhood cancer survivors (AT-Survivors) have reduced left ventricular (LV) mass and elevated LV afterload which can lead to LV dysfunction. These changes may be exacerbated by factors impairing LV hypertrophy such as growth hormone (GH) insufficiency, which can Results from cranial irradiation (Cr-Irr). We hypothesized Cr-Irr exposed AT-Survivors would have worsened LV abnormalities and that IGF-1, a marker of GH, would be more strongly correlated with these changes in those exposed.
Methods: AT-Survivors from a NCI cohort study in Rochester, NY had echocardiograms recorded as age, sex, and body-surface area-adjusted z scores and IGF-1 recorded as the difference from the normal age-expected value. AT-Survivors were grouped by Cr-Irr exposure. Group means of LV measures were compared by t-tests and mean differences adjusted by regression. Group-specific correlation coefficients for LV measures with IGF-1 were compared.
Results: Of 132 AT-Survivors, 61 had Cr-Irr exposure (median dose, 18 Gy). Both groups were of similar mean age (17.3 vs. 18.1 yr, P=.56), age at diagnosis (7.0 vs. 7.6 yr, P=.55), and time from diagnosis (10.3 vs. 10.5 yr, P=.85). Exposed AT-Survivors were less likely female (43 vs. 62%, P=.03) or to have received cardiac irradiation (23 vs. 32%, P=.23) but received higher total mean anthracycline doses (5.5 vs. 5.3 log mg/m2, P=.15). Exposed AT-Survivors had reduced LV mass, non statistically significantly (NS) reduced LV wall thickness and dimension (Table), and lower IGF-1 (−75.4 vs. −8.4 ng/mL, P<.01). The associations of these LV measures with IGF-1 was stronger, often NS, in exposed AT-Survivors (Table).
Conclusions: Cr-Irr exposure in AT-Survivors is associated with reduced LV mass and other cardiac abnormalities that are correlated with a marker of decreased GH. Over time, this added stress and impaired compensation may increase this group's risk of heart failure and vulnerability to cardiac insults.
- © 2010 by American Heart Association, Inc.