127 Summarized discussion and future perspectives. Future perspectives My thesis focussed on cardiac toxicities. They are relevant as they can influence both overall survival and quality of life in different ways. Moreover, these different toxicities have various relationships with radiation dose distributions. Prioritizing these toxicities, and the associated organs at risk remains a challenging issue. In EC, the total toxicity burden has been proposed as a composite endpoint of different toxicities and was used in clinical trials[18,19]. This total toxicity burden prioritized different complications and weighted them by their severity. More serious toxicities were assigned higher scores, and eventually were summed up per patient. In the future, this total toxicity burden can be used in clinical trials as an endpoint in evaluating, for example, new technologies. Another endpoint which is very relevant for individual is quality of life (QOL). QOL could reflect the combined impact of different toxicities in the treatment of EC cancer. Within the CROSS trial, the largest trial randomizing patients between neoadjuvant chemoradiotherapy followed by surgery and surgery only, no significant differences in QOL at different time points during the first year after treatment were found [31]. This was explained by the relatively low prescribed radiation dose in combination with mild chemotherapy, but it should be noted that the authors reported lower compliance rates to the QOL questionnaires in the surgery only group. Poor compliance rates are an important source of bias in QOL studies as both patients having a poor performance as well as patients not suffering any side effects will be less tentative responding on questionnaires. Moreover, QOL scores were not scored during treatment, for example during hospitalization post-surgery or during CRT. In a QOL meta-analysis among patients treated with definitive CRT, baseline values were lower as compared to the standard population. However, these values did not decline during follow up despite a relatively high rate of late toxicities seen after treatment. Taking these findings into consideration, one could question whether QOL scores are a representative method to evaluate radiation-induced complications of EC patients [32]. Finally, the question remains what endpoints should be considered most relevant, both for patients and as endpoint for future clinical trials. Overall survival probably qualifies as it is an objective unbiased endpoint which is most relevant and easy to score. Several recent modelling studies indeed used overall survival as an endpoint and found radiation dose parameters to be a predictor for overall survival in intrathoracic tumours in multivariate analyses [33–36]. Although this suggests 8
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