109 Blood biomarkers during and after treatment We did not find any significant associations between the QOL endpoints and changes of lab values, clinical events or DVH parameters. Discussion The aim of this study was to test the hypothesis that the levels of NT-proBNP and HS-TNT increase after radiation therapy as a function of radiation dose. To evaluate whether these biomarkers can be helpful to detect cardiopulmonary toxicity, associations between these biomarkers and cardiac events and/or death were evaluated as well.The results suggest that both HS-TNT and NT-ProBNP are associated with the development of cardiopulmonary events, as the rise of both biomarkers after treatment was related to non-tumor related death as well as to new cardiac events. However, whether these markers can be used for early detection of cardiopulmonary toxicity remains to be determined. The rise of these markers during treatment was not significantly associated with these events, nor with non-tumor related death at later time points. Given the limited number of patients available at follow up and the trends seen in the longitudinal analyses, it is worthwhile to perform larger studies to gain more insight in the relationship between different factors and events. Different mechanism may be responsible for changes over time in the cardiac blood biomarkers. First, the rise of HS-TNT over time was significantly associated with cardiac radiation dose, suggesting direct radiation-induced cardiac damage. Secondly, NT-ProBNP was related to radiation dose to the lungs suggesting indirect mechanisms affecting the heart. Preclinical data showed that radiation exposure to the lungs resulted in higher vascular resistance in the lungs, which increased the pressure in the entire cardiovascular system [26,27]. This is supported by the fact that NT-ProBNP is a known marker for cardiac failure, which may also result from increased vascular resistance in the lungs and pulmonary hypertension. At later time frames, the rise of these biomarkers was associated with clinical cardiac events. Unfortunately, the overall survival of our study population was worse than expected and thus the number of patients left at 12 months after treatment was too low for proper analyses. Consequently, we focused on the analysis up to 6 months after treatment. Furthermore, this dataset was not sufficiently powered to correct for multiple confounding factors, like whether or not an esophagectomy was performed after neoCRT. As mentioned in the results section, patients who 7
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