Characteristics of Blood Levels of Vascular Endothelial Growth Factor A (VEGFA) and Its Receptors in Men with Malignant Brain Gliomas with Different Responses to Combination Therapy

Abstract

Relevance: Glial tumors (GTs) amount for about 60 % of all primary CNS tumors. GTs highly express VEGF. Standard approaches to GT treatment do not involve modification of the radiation therapy plan. Adaptive stereotactic radiotherapy (ASRT) allows such correction. The combination of ASRT with bevacizumab (B) or dexamethasone (D) improves the outcomes of patients with GTs, but the effectiveness of therapy varies from patient to patient. B and D are known to have different effects on malignant glioma cells and components of the VEGF system.Purpose: To reveal specific levels of the VEGF system components in the blood of men with cerebral GTs with different effectiveness of combination ASRT.Material and methods. One month after radical surgery, men with GTs received ASRT with standard fractionation on the Novalis Tx linear accelerator (Varian): single fraction dose = 2 Gy, total dose = 60 Gy, 30 fractions, using a three-layer stereotaxic mask. ASRT was combined with B (i/v, 5 mg/kg, once every 2 weeks), n = 30, and with D (i/m, 4 mg, twice a day during 45 days), n = 30. Blood levels of VEGFA, sVEGFR1 and sVEGFR2 were measured by IFA before and after ASRT.Results: Before treatment (ASRT+D), levels of VEGFA were 1.5 times (р < 0.01) higher, and sVEGFR1 was 3.1 times lower in patients with future progression, compared with patients with other responses to treatment; in partial response, sVEGFR was 1.8 times (р < 0.01) higher than in stabilization. After treatment (ASRT+D), sVEGFR1 levels reduced by 1.4 times (р < 0.001) in stabilization and by 2.2 times in partial response, together with VEGFA increase by 3.0 times in stabilization only; in progression, sVEGFR1 increased by 2.3 times. Before treatment (ASRT+B), levels of VEGFA in patients with partial and complete responses were on average 1.4 times (р < 0.01) lower than in stabilization; sVEGFR1 in partial response was 4.4 times lower than in stabilization and 2.2 times lower than in complete response; sVEGFR2 in complete response was 1.3 times (р < 0.02) lower than in partial response. After treatment (ASRT+B), VEGFA levels elevated: in complete and partial responses on average by 14.8 times, in stabilization by 9.7 times.Conclusions: In men with cerebral GTs, blood levels of the VEGF system components before treatment differed in patients with different future responses to combination ASRT with B or D, which allows prediction of the effectiveness of such therapy even before it is started. This connection is especially obvious for combination ASRT with B.