89 Late cardiac toxicity in survivors of esophageal cancer Discussion The aim of this hypothesis-generating pilot study was to identify late subclinical cardiac toxicity after nCRT for esophageal cancer. An overview of these results is visualized in Figure 2. The results suggest an effect on myocardial fibrosis and an increased rate of AF. In this small population of patients treated with nCRT followed by surgery, the prevalence of AF was higher than after surgery alone (p=0.07 (corrected for age)). These findings are in line with those from several previous reports, showing an increased incidence of AF after thoracic irradiation [13,32–34]. Figure 2 Overview of relevant findings There might be a causal relationship between myocardial fibrosis and the development of AF. Most patients who develop AF have fibrosis in the atrial wall (e.g. as a consequence of hypertension, valvular disease and atrial dilatation[35]). When looking at the patient group with AF in the current study, a relatively high radiation dose was given to the atria because of its close proximity to the target volume. Given the linear dose response relationship with fibrosis that we found in the left ventricular myocardial wall [31], it is likely that the atrial walls developed fibrosis as well. These findings are supported by preclinical studies, in which fibrosis was associated with decreased end diastolic diameter of the irradiated atria [36]. Unfortunately, ECV cannot be measured in an atrial wall since the walls are too thin. Although both mechanisms (wide atria as measured by LAVI and radiation dose to the atria) were only related to AF with borderline significance in this population, we evaluated these variables both in a multivariate analysis and found that they became statistically significant with high discriminating power (AUC 0.93). These 6
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