116 Chapter 8 Summarized discussion and future perspectives The aim of this thesis was to get more knowledge on the relevance and mechanisms of cardiac toxicity in the treatment of esophageal cancer (EC). Hopefully, this work will contribute improving radiotherapy treatment planning by enabling educated trade-offs between heart and lungs doses. This thesis includes a review of the available literature and reports on the results of three clinical trials. Chapter 2 contains an overview of the literature at that time (2015) reporting on incidences and the spectrum of cardiac toxicities seen after (chemo)radiotherapy with or without surgery. These papers reported relatively high incidences of cardiac toxicities. In most papers, a relation with radiation dose volume parameters of the heart was found using different cut of values. However, at that time, no normal tissue complication probability (NTCP) models were published. These results, as well as more recent papers are incorporated in the discussion hereafter [1]. In chapter 4, we report on the results of a retrospective analyses on 216 patients treated with chemoradiotherapy for EC. Cardiac dose volume parameters predicted the risk on pericardial effusion, whereas pulmonary dose volume parameters predicted the risk of radiation pneumonitis. Overall survival was significantly worse for patients presenting with a radiation-induced pneumonitis (p=0.01). Patients developing pericardial effusion, had similar overall survival as compared to patients who did not develop pericardial effusion. In the multivariable prediction model for overall survival, lung dose volume parameters remained significant next to tumour stage, in contrast to cardiac dose volume parameters. These results suggest that reducing the cardiac dose at the expense of the lungs might not always be a good idea [2]. In chapter 5 and 6, we focussed on late toxicity in EC survivors after multimodality treatment. In this cross-sectional (CROSS SECT) study, we evaluated clinical and subclinical damage of the heart in twenty patients treated with surgery alone, as compared to twenty patients who were treated with neoadjuvant chemoradiation followed by surgery . In chapter 5 we investigated the association between radiation dose and myocardial fibrosis as measured by the extracellular volume (ECV) on cardiac MRI. These ECV values are considered a surrogate for histologic collagen burden in the myocardium.
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