26 Chapter 2 The high complication rates in these retrospective studies were not confirmed by prospective (randomized) esophageal cancer trials. This could be explained by the relatively simple radiation delivery techniques used in most of the retrospective studies. Moreover, the total dose was relatively high, 60 Gy in 3 out of the 6 papers, versus 50.4 Gy which is currently the standard in many European countries and the USA. On the other hand, it is very likely that cardiac morbidity was poorly reported in the older trials because the relationship with the given treatment was not well acknowledged at that time. Studies reporting on randomized preoperative CRT do not provide much additional information regarding toxicity. Most of these trials had relatively low patient numbers . In meta-analyses, only postoperative morbidity, mortality and overall survival have been reported.[15–18]. Furthermore, the two largest trials , have a relative short follow up and one of them has not even been fully published. [18,19] Bosch et al. on the other hand focused more specifically on chemoradiation-induced morbidity. They retrospectively compared 96 patients treated with preoperative CRT (41.4 Gy/carbo/taxol) with matched controls who were treated with surgery only.[20] In this study, rates of pneumonia, cardiac arrhythmia and pleural effusion were observed more frequently in the preoperatively treated group. Despite these events, no differences in hospital stay or short-term mortality were found, which is in line with the meta-analysis data. On the other hand, in a meta-analysis investigating the role of postoperative radiotherapy for lung cancer, a relative increase in mortality of 21% was found in the irradiated group.[21] Although the authors were unable to analyze causes of death in this meta-analysis, non-cancer-related causes of death were suggested since the local recurrence rates were reduced by postoperative radiotherapy. The latter might be a relevant finding for the treatment of esophageal cancer as target volumes for lung cancer are comparable with those for esophageal cancer. As mentioned previously, it is not always clear if cardiac events are actually related to radiation treatment. A strong argument for radiation-induced cardiac toxicity in this patient group is the association with dose-volume parameters. Based on the current literature, however, it remains difficult to determine the most relevant dose parameter. An important reason is probably that the toxicities – and thus the endpoints – used in these studies were diverse. It is very unlikely that focal wall motion disorders as seen in the imaging studies correspond to the same DVH parameters as the risk of developing pericarditis.
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