Radiosurgery reduces plasma levels of angiogenic factors in brain arteriovenous malformation patients

Abstract

PurposeAberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-β, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. MethodsWe enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-β, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. ResultsThe baseline plasma VEGF content was 222.63 pg/mL (range 43.25–431.25 pg/mL). At three months post surgery, there was a significant −34.29% decline in plasma VEGF content versus baseline (P = 0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm3) than those with a nidus volume < 10 cm3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P = 0.057]. The baseline plasma TGF-β content was 556.17 pg/mL (range 44.44–1486.11 pg/mL) and there was a significant −27.47% decline in plasma TGF-β content at 3 months post radiosurgery versus baseline (P = 0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14–453.76 pg/mL). There was an immediate and significant −12.47% decline in plasma ANG-2 content post surgery versus baseline (P = 0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline (P = 0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67–36.78 pg/mL). No significant difference in plasma bFGF content was observed immediately post surgery and 3 months post surgery versus baseline (P = 0.05). ConclusionsRadiosurgery for brain AVM patients significantly reduced the plasma levels of angiogenic factors. The plasma angiogenic factors may be candidate markers for aberrant agniogenesis of brain AVM and patient response to radiosurgery.