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.