Prophylactic Bevacizumab May Mitigate Radiation Injury: An Experimental Study.

Abstract

Stereotactic radiosurgery (SRS) is widely used to treat brain pathologies alone or in concert with other treatment modalities. However, there are some side effects, such as radiation injury characterized by edema and necrosis in peripheral tissues, that must be managed. A new treatment agent against this side effect is bevacizumab, which targets increased vascular endothelial growth factor (VEGF) as a prominent etiologic factor in radiation injury. In this study, we created a rat experimental model to describe the effects of both radiation and the anti-VEGF monoclonal antibody bevacizumab following high-dose SRS, and to compare the effects of prophylactic and delayed-onset bevacizumab treatment. Fifty-four adult male Wistar rats were allocated into 9 groups based on differing Gamma-knife surgery (GKS) doses and bevacizumab treatment protocols. After 12 weeks, the rats' right frontal lobes were examined with hematoxylin and eosin staining and immunohistochemistry analysis via VEGF and CD31 antibodies. Radiation necrosis occurred to varying degrees in all irradiated animals between 3 and 10 weeks post-SRS. Higher GKS dose (50% isodose of 100 Gy) led earlier necrosis and prophylaxis of bevacizumab at this dose was associated with delayed onset of necrosis. Moreover, prophylactic bevacizumab mitigated the effects of radiation necrosis following GKS at both doses, whereas this effect was not prominent with late initiation of bevacizumab (treatment protocol). Our findings show that the onset and degree of radiation injury are affected by the GKS dose and protocol of bevacizumab administration.