CHAPTER 7 172 DISCUSSION In this study, the prognostic and predictive relevance of preoperative abnormal haematological parameters in patients with EC was evaluated. Anaemia was identified as an independent prognostic factor for DSS, along with age and ESGO/ESTRO/ESP ‘high- and advanced/ metastatic’ risk. Furthermore, anaemia seemed an overall predictive factor for response to adjuvant RT, and specifically for patients with ESGO/ESTRO/ESP intermediate risk who received solely VBT. Although most patients with EC present with postmenopausal bleeding as an early symptom, this rarely causes anaemia at diagnosis. Hence, the development of cancer-related anaemia in EC is more likely caused by inflammatory cytokines which results in a shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin (EPO) production.12, 30 Anaemia in patients with an absolute or relative EPO deficiency seems to be more aggressive in solid tumours.31 Therefore, it is suggested that preoperative anaemia in EC could be a biomarker of tumour burden and/or aggressive tumour behaviour.30, 31 In our study cohort we observed that patients with anaemia were significantly more often allocated to ESGO/ESTRO/ESP high risk group, grade 3 EC, and the presence of LVSI. In both univariable and multivariable DSS analysis, we found anaemia as independent prognostic factor. To our knowledge, the presence of anaemia has so far not been related to the ESGO/ESTRO/ESP risk groups. Previous studies did show a significantly higher prevalence of anaemia in patients classified into the ESGO/ESTRO/ESP high risk group; FIGO advancedstage, grade 3 EC and LVSI.21 The 5-year RFS was significantly reduced in patients with anaemia compared to those without anaemia. However, anaemia was not an independent prognostic factor for the RFS, comparable to the findings of Wilairat et al. (2012)32 Cancer-related anaemia may also cause tumour hypoxia, which may lead to a reduced response to RT.9, 22-24 Normally, hypoxia will lead to an EPO increase, however due to the cancer-associated inflammation the EPO production is insufficient and the iron metabolism is impaired. VBT is given for local control of the tumour and EBRT could be applied to control locoregional recurrence.24 In patients within our study who received RT and even with solely VBT within the ESGO/ESTRO/ESP intermediate risk group, anaemia was correlated with a significantly reduced DSS. However, numbers were low and therefore multivariable analysis was not achievable. So far, no other studies including EC patients have been performed to compare our findings. Three recent meta-analyses published the clinicopathological and/or prognostic significance of preoperative thrombocytosis in EC.13, 14, 18 In line with our findings, a significant association of thrombocytosis with FIGO advanced-stage, LVSI and grade 2-3 EC was found.13, 18 The
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