VEGF-blockade of localized Ewing’s sarcoma based on angiogenesis markers in pretreatment tumor tissue

A third of patients with localized (non-metastatic) forms of tumors of the Ewing sarcoma family (ES) have resistance to modern systemic therapy regimens, which leads to a relapse of the disease. Forecasting such cases for the purpose of timely intensification of treatment is possible by studying the biology of the tumor process  and in particular angiogenesis (AG) – the process of formation of the tumor by the own vascular network. Earlier, we found that the level of AG markers (TFPI2 mRNA expression (tissue factor inhibitor) and the ratio of VEGFA165/VEGFA189 vascular endothelial growth factor  isoforms) in the tumor tissue prior to treatment can differentiate  patients. Previously we have established the ability to predict poor  outcome based on mRNA expression levels of both TFPI2 (tissue  factor pathway inhibitor 2) and VEGFA165/VEGFA189 (vascular endothelial growth factor isoforms) ratio in pretreatment tumor tissue, it makes it possible to differentiate patients from localized ES into groups of favorable and unfavorable outcome of the disease.

The aim of this study was to intensify treatment by blockade of AH for patients with an adverse outcome predicted by the level of AH markers. VEGF-blockade was used to enhance the therapeutic effects for patients with a predicted adverse outcome. 29 patients with  localized forms ES included in the study. For patients with adverse prognosis (51.7 %) standard chemotherapy has been strengthened through bevacizumab (VEGF inhibitor). 5-years Event-free survival  (EFS) for patients with adverse prognosis was 66.7 % for patients  with good prognosis – 100 %, for all patients EFS rate was 82.4 %.  EFS of the combined cohort of patients was 82.8 %. It was shown  that anti-angiogenic therapy can be effective in patients with  localized forms of ES with a predictable (based on the level of AH markers) adverse outcome of the disease.

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