Abstract
Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). 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. Seventeen nCRT and 16 control patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (P = .02). In nCRT patients, we found a significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (P < .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 Gy (P < .001). There were no differences in LV function measures and late gadolinium enhancement between both groups. Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared with surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.
Highlights
The clinical introduction of neoadjuvant chemoradiotherapy before surgery provided an important survival benefit for patients with esophageal cancer (EC).[1]
In 1 control patient, the basal slice was scanned too close to the mitral valve, and these segments were excluded because of partial-volume artifact basal segments
This study shows for the first time a linear doseeresponse relationship between mean radiation dose per left ventricular (LV) myocardial segment and Extracellular volume (ECV)
Summary
The clinical introduction of neoadjuvant chemoradiotherapy (nCRT) before surgery provided an important survival benefit for patients with esophageal cancer (EC).[1] recent studies have shown that there is a substantial risk of cardiac toxicity and even mortality attributable to nCRT that potentially jeopardizes the benefit of nCRT.[2,3,4,5,6] Wang et al.[6] reported grade !3 cardiac events in 18% of patients with EC who were treated with chemoradiotherapy. Radiation modality (hazard ratio: 1.7) or mean heart dose (hazard ratio: 1.03) were significantly associated with these complications. Patients who developed these cardiac complications had worse overall survival (OS; 5 years OS: 38% vs 52%). The exact mechanism of toxicity underlying this increased risk of cardiac complications remains unknown.[7] Knowledge on these mechanisms might help reduce the toxicity risks, aiming to maximize the benefit of nCRT and improve survival in patients with EC
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