99 Blood biomarkers during and after treatment Introduction The relevance of radiation-induced cardiopulmonary toxicity has been acknowledged for years. Numerous studies have shown a relationship between either radiation technique or dose and cardiopulmonary toxicity and overall survival [1–4]. However, the exact mechanisms and course of radiation-induced tissue damage remain to be determined [5–7]. Cardiac biomarkers serve as an easy and fast screening method for the diagnosis of heart diseases. Elevated troponins, like High Sensitive Troponin T (HS-TNT) are considered biomarkers for myocardial necrosis and are established prognostic factors for heart failure and overall survival [8,9]. In addition, N-terminal Brain Natriuretic Peptide (NT-ProBNP) is considered an early biomarker for heart failure and is a prognostic factor for cardiac events and overall survival [10–12] . These biomarkers have been studied extensively in oncologic patients receiving chemotherapy. HS-TNT levels are higher after cardiotoxic chemotherapy, like Adriamycin and HER-2 Neu inhibitors[13], while elevated HS-TNT levels are associated with decreased left ventricular (LV) function [14]. Therefore, these biomarkers have been advocated by the European Cardio-Oncology Study Group for its use in risk assessment and diagnosis of cardiovascular disease in cardiotoxic cancer treatments [13]. However, limited data exists on the association between radiationinduced toxicity and these biomarkers. The available literature suggests a role for NT-ProBNP, as it rises after radiotherapy treatment, but a relation with radiation dose was reported in only three out of nine papers [15–23]. A rise in HS-TNT levels after radiotherapy treatment was only reported in two out of these nine papers, while a relation with radiation dose could only be confirmed in one paper [Skytta et al]. However, these 9 studies were relatively small, and in most papers breast cancer patients were included, in which the dose to the heart is relatively low. Furthermore, in some studies, baseline values were missing, or patients were pretreated with systemic agents. The results of these studies are summarized in Table 1 of the supplementary data. In esophageal cancer patients, the radiation dose to the heart is relatively high, and patients share common risk factors for cardiovascular diseases. Because of the potential role of cardiac biomarkers in the diagnosis of cardiac injury and its relationship with prognosis in cardiologic literature, we designed this prospective longitudinal study to evaluate whether standard use of these biomarkers could be helpful to evaluate cardiac toxicity during and after intrathoracic radiotherapy. 7
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