ABNORMAL HAEMATOLOGICAL PARAMETERS IN EC 161 7 INTRODUCTION Endometrial cancer (EC) is the most common gynaecologic malignancy in industrialized countries with incidence rates rising due to aging and obesity. Most patients are diagnosed with low-grade EC (grade 1-2 endometrioid EC), and generally have a favourable prognosis.1 Around 20% of patients are diagnosed with high-grade EC (grade 3 endometrioid EC and non-endometrioid EC), have an overall poor prognosis and are associated with an increased risk of regional or distant metastases.1 Currently, primary surgical treatment is based on preoperative tumour grade and histology. Yet, in some patients fertility preservation could be considered based on: (I) grade 1 tumour histology, (II) tumour restricted to the endometrium by imaging, (III) no contra-indications of hormonal treatment, (IV) counselling about not the standard care of EC, including the risks. Patients with high-grade EC or with deep myometrial invasion are not recommended for fertility preservation treatment due to high risk of nodal metastasis.2, 3 Immunohistochemical or molecular markers could be additional helpful facilitate decision making for fertility-sparing treatment.2-6 According to the recent ESGO/ESTRO/ESP (European Society of Gynaecological Oncology – European SocieTy for Radiotherapy and Oncology – European Society of Pathology) guideline, adjuvant treatment is based on risk classification groups incorporating FIGO (Federation International of Gynecology and Obstetrics) stage, tumour grade and histology, lymphovascular space invasion (LVSI) and with or without molecular markers.7 Often routinely obtained preoperative clinical biomarkers, such as haematological parameters, may contribute to identification of patients with extended disease and/or aggressive tumour behaviour that might respond differently to adjuvant therapy.8-10 Endometrial carcinogenesis is characterized by chronic inflammation with elevated proinflammatory cytokines and acute phase proteins.11 Overexpression of inflammatory cytokines could contribute to the development of cancer-related anaemia, thrombocytosis and leucocytosis, and could generate a pro-tumorigenic environment.12-15 Preoperative abnormal haematological parameters like anaemia, thrombocytosis and/or leucocytosis, have been shown to be associated with FIGO advanced-stage and unfavourable outcome, however results remain conflicting.13, 14, 16-21 Several studies showed an adverse impact of anaemia to radiotherapy (RT) response in solid tumours, explained by the fact that anaemia is proposed to be a surrogate maker for tumour hypoxia.9, 22 Hypoxia is very common in solid tumours and leads to cellular stress response, which allows tumour cells to survive. In addition, these hypoxic conditions may also protect tumour cells from downstream DNA breaks and lethality induced by radiotherapy.23, 24 Within gynaecological tumours, leucocytosis was also observed to have an adverse predictive impact
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