51 Retrospective analyses on toxicity in esophageal cancer patients Discussion In this paper, we aimed to identify clinical and/or dosimetric parameters that are related to cardiac and/or pulmonary toxicity in oesophageal cancer patients and analysed its effect on overall survival. The total prescribed dose in this patient group was relatively high which explains the OS compared favourable to the literature and the relatively high complication rates in this patient group. This allowed us to develop a multivariable prediction model for both heart and lung toxicity and report a comprehensive analysis of these toxicities in oesophageal cancer patients. Cardiac and pulmonary toxicities are clinically relevant side effects and decisions on the preferred dose distribution in an individual patient should be based on the risk of toxicity of both organs at risk. Regarding pulmonary toxicity, there is only limited data on the risk of radiation pneumonitis in oesophageal cancer patients treated with definitive CRT. The published papers do not provide an odds- or hazard ratio for radiation pneumonitis in this patient group [20,21]. Our model on pericardial effusion is in line with other retrospective publications [7,22,23]. Dose response relationships with different cardiac dose parameters were described in all of these publications. Hayashi, et al. presented the odds ratios of several cardiac DVH parameters related to PE. Our odds ratios seemed to be slightly lower but remained within their 95% confidence intervals[22]. Wei, et al. analysed doses both to the pericardium and whole heart and also found a stronger association for the pericardial dose vs. mean heart dose on PCE, indeed suggesting a local inflammatory effect[23]. To determine which toxicity is most relevant and consequently which organ at risk should be prioritized in our planning strategies, we finally focused on OS as an endpoint. In the multivariable analysis, we found that the dose to the lungs but not the radiation dose to the heart influenced OS significantly in this patient population. Moreover, the subgroup of patients with radiation pneumonitis had a worse OS in Kaplan Meier analysis, as opposed to the patients diagnosed with pericardial effusion, a side effect which did not seem to influence OS. However, when repeating the survival analyses censoring patients with a RP, the same variables remained significant for OS, suggesting the clinical diagnosis of radiation pneumonitis itself might not be the cause for worse OS. In the patient group presenting with radiation pneumonitis, we found the heart dose the most important predictor for OS. 4
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