60 Chapter 5 Abstract Purpose: Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there us a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation(nCRT) for esophageal cancer(EC). Materials and methods: Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included. Cardiovascular magnetic resonance imaging (1.5 Tesla) for left ventricular (LV) function, late gadolinium enhancement, and T1 mapping were performed. Extracellular volume (ECV), as a surrogate for collagen burden, was measured for all LV segments separately. The dose-response relationship between ECV and mean radiation dose per LV myocardial segment was evaluated using a mixed-model analysis. Results: Seventeen nCRT and 16 control group patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (p = 0.02). In nCRT patients, we found an significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (p<0.001). After nCRT, LV myocardial segments with elevated ECV had received significantly higher radiation doses. In addition, a linear dose-effect relation was found with a 0.136% point increase of ECV for each Gray (p<0.001) There were no differences in LV function measures and late gadolinium enhancement (LGE) between both groups. Conclusion: Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared to surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.
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