Cardiac Radiation Dose In Pediatric Cancer Patients Is Associated With Tricuspid Regurgitation And Decreased Left Ventricular Wall Thickness

Incidental cardiac radiation therapy (CRT) is associated with increased risk for cardiovascular disease including valvular disease, coronary artery disease, and diastolic dysfunction. These outcomes are magnified in long-term pediatric cancer survivors. Anthracycline (ATC) induced myocyte dropout, and radiation induced interstitial fibrosis and capillary loss are presumed to be etiologic. Limited data are available that dissect morphometric and physiologic parameters of dysfunction. This study begins to quantify the dose effect of CRT and further characterize interactions with ATC on the developing heart. A National Cancer Institute supported Cardiac Risk Factors in Pediatric Cancer Survivors Study prospectively studied 277 childhood cancer survivors >5 years from treatment and 76 sibling controls for multiple risk factors. Mean age was 9.07 years at diagnosis, and 20.8 years at follow-up. CRT doses ranged from 4 Gy to 46.8 Gy, with a mean of 23.8 Gy. Survivors were divided by treatment received: ATC and CRT, ATC alone, CRT alone, and neither ATC nor CRT. This study examined only those cohorts that received either ATC + CRT (n = 28), or CRT alone (n = 17). Subjects underwent complete echocardiographic examination: Left Ventricular Fractional Shortening (LVFS), LV Mass (LVM), LV Afterload (AL), Contractility (CT), and LV Wall Thickness (WT) were converted into z-scores normalized to the sibling control cohort. Degree of Mitral Stenosis (MS), Mitral Regurgitation (MR), and Tricuspid Regurgitation (TR) was measured using a 5-point scale (0–4). Correlation coefficients were calculated between these parameters and CRT dose. A positive or negative correlation of >20% with a p-value of <0.05 was considered significant. Correlations between the echocardiographic variables and CRT dose are shown with respective p-values in the table(table 1). CRT dose was negatively correlated with LVM and WT for those who received both ATC and CRT. Both LVM and WT decreased with increasing CRT dose in those who also received ATC. These correlations suggest a dose-response relationship with CRT as potentiated by ATC. In the CRT-alone group, CRT dose was positively correlated with tricuspid regurgitation. AL, LVFS, CT, MR, and MS showed no correlation with dose. Combined CRT and ATC are associated with a dose-dependent decrease in WT and LVM. No significant correlations were demonstrated between CRT dose and LVFS, AL, CT, or mitral dysfunction, suggesting that these patients are well compensated at this point in time. These findings validate the need for continued screening, as this high-risk population ages. Except for TR, our data show no abnormality in physiology or morphometry with CRT alone. We observed significant interaction when CRT was combined with ATC. Further research describing CRT dose distribution to specific cardiac structures and interaction with ATC is in process.