CHAPTER 8 188 relevant within the molecular subgroups, particularly in p53mut and NSMP subgroup. In this study, a predefined cutoff for ER/PR expression, with improved prognostication, was used. Cutoff 0-10% with unfavorable outcome, 20-80% with intermediate outcome and 90-100% with favorable outcome.55 Among all molecular subgroups, patients with ER+PR 0-10% expression showed the worst DSS and ER+PR 90-100% expression an excellent 5-year DSS, interestingly even within p53mut tumors. In multivariable analyses, ER+PR 0-10% was in addition to p53mut, lympho-vascular space invasion (LVSI) and FIGO stage an independent prognostic factor for reduced DSS. ER+PR 90-100 was in addition to POLEmut an independent prognostic factor for improved DSS. These data confirms our hypothesis that ER/PR expression would be preferably divided in three subgroups instead of the mostly used ≤1% and >1% or ≤10% and >10%, and underline the retained relevance in addition to the molecular subgroups, potentially guiding adjuvant treatment such as hormonal therapy as proposed in the RAINBO trial.61 Cancer-related anemia may cause tumor hypoxia, which could lead to a reduced response to radiotherapy (RT).62-65 Hypoxia is very common in solid tumors and leads to cellular stress response, which allows tumor cells to survive. In addition, these hypoxic conditions may also protect tumor cells from downstream DNA breaks and lethality induced by radiotherapy.64, 65 Therefore, it is hypothesized that preoperative anemia in EC could be a biomarker of tumor burden and/or aggressive tumor behavior.66, 67 Within gynecological tumors, leukocytosis was also observed to have an adverse predictive impact on RT response.68 In chapter 7 the predictive relevance of hematological parameters within EC was analyzed. Patients with anemia and adjuvant RT had a significantly reduced DSS compared to patients with a normal hemoglobin. However, numbers were low and multivariable analysis could therefore not be performed. These data suggest that more research is required in EC patients assessing the effect of anemia on adjuvant RT treatment and incorporation of anemia in the risk stratification models for adjuvant treatment.
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