Bevacizumab for refractory adverse radiation effects after stereotactic radiosurgery

Abstract

To retrospectively evaluate the clinical benefit and imaging response of bevacizumab when used to treat refractory adverse radiation effects (ARE) after stereotactic radiosurgery. Twenty-nine patients with brain tumors or vascular malformations developed clinical and/or imaging evidence of ARE after SRS and were treated using bevacizumab. Patients received an average dose of 7.4 mg/kg over a mean of 5.7 weeks at a median of 16 months following SRS. Initial diagnosis, SRS dose, bevacizumab treatment protocols, magnetic resonance imaging T2/FLAIR and T1 paramagnetic contrast enhanced edema volumes were compared before and after bevacizumab administration. Ninety percent (18/20) with clinically symptomatic ARE had neurological improvement after bevacizumab therapy. Twenty-six patients had a decrease of 62 % of T2/FLAIR volumes and a 50 % decrease in magnetic resonance imaging intravenous contrast enhancement volumes. Two patients showed progression of the T2/FLAIR and contrast enhancement volumes. One patient had progression of post-Gd-enhancement but regression of T2/FLAIR volume. Symptoms recurred in 11 of the 20 patients after discontinuing therapy. Patients who experienced a return of enhancement received a lower marginal dose during SRS. Our experience provides additional evidence that bevacizumab reduces both symptoms and reactive imaging changes in patients with ARE. After SRS, refractory ARE unresponsive to initial corticosteroids or other agents may benefit from a bevacizumab trial. The necessary duration and optimum dose of therapy is unknown and provides a further impetus to conduct a prospective trial.