Bevacizumab for radiation necrosis following treatment of high grade glioma: a systematic review of the literature

Abstract

This review identifies the current literature on the use of bevacizumab for cerebral radiation necrosis in patients with high-grade gliomas, summarizes the clinical course and complications following bevacizumab, and discusses the relative costs and benefits of this therapeutic option. A Medline search was conducted of all clinical studies before September 2012 investigating outcomes following use of bevacizumab therapy for radiation necrosis in patients with high-grade gliomas. Clinical and radiographic outcomes are reviewed. Seven studies reported a total of 30 patients with high-grade gliomas treated with bevacizumab for radiation necrosis. All patients demonstrated decreased radiographic volume of edema on T1 and T2 MRI sequences. Clinical outcomes were reported for 23 patients: 16 (70 %) had improvement in neurologic signs or symptoms, 5 (22 %) had mixed results, and 2 (9 %) remained neurologically unchanged. Complications were documented in 5 of 7 studies (18 of 29 patients, 62 %) and included deep vein thrombosis, pulmonary embolism, visual field worsening, worsening hemiplegia, pneumonia, seizure, and fatigue. Only one study evaluated quality of life measures and none evaluated cost or cost effectiveness. Data regarding the use of bevacizumab to treat radiation necrosis in patients with high-grade gliomas is limited and primarily class III evidence. While bevacizumab improves neurological symptoms and reduces radiographic volume of necrosis-associated cerebral edema, it comes at the expense of a high rate of potentially serious complications. Definitive evidence for the utility, cost-effectiveness, and overall efficacy of this management strategy is currently lacking and additional investigation is warranted.

Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation

“…Consistent with prior clinical investigations [7–10], anti-VEGF treated mice show remarkable decreases of RN lesion volume, detected radiographically on both post-contrast T1W and T2W images (Fig. 1).…”

“…Traditional treatments of RN, including corticosteroids and hyperbaric oxygen, are associated with significant toxicity and limited efficacy [23]. Recently, multiple groups have investigated the treatment effect of anti-VEGF antibody (i.e., bevacizumab), which blocks VEGF from reaching its capillary target and is, thus, hypothesized to reduce vascular leakage and associated brain edema, on radiographic volumes of RN clinically [7–10]. The work presented herein is distinct from prior clinical studies in that the Gamma Knife mouse RN model is a single hemisphere radiation injury model, which allows (i) direct comparisons with the non-irradiated hemisphere and (ii) histological validations that are impractical for clinical cases.…”

“…While bevacizumab improves neurological symptoms and reduces the volume of RN-associated vascular leakage and resultant edema detected radiographically, the treatment brings with it potentially serious complications [10–12]. For instance, bevacizumab treatment increases the risk of hemorrhage and retards wound healing by impairing neovascularization, which are critical concerns for neurosurgeons [12, 13].…”

Radiothérapie en conditions stéréotaxiques des métastases cérébrales

“…Il n'y a pas de traitement « curatif » de la radionécrose, les corticoïdes à la dose de 1 mg/kg pour une durée d'au moins un mois, la pentoxifylline, le bévacizumab à faible doses (5 mg/kg toutes les trois semaines) [37,38], ainsi que la chirurgie sont les traitements les plus souvent recommandés. Des arbres décisionnels ont même été proposés [30].…”

Hyperbaric Oxygen for Radiation Necrosis of the Brain

“…Patients who are asymptomatic can be observed, while those who are symptomatic are managed with corticosteroids, hyperbaric oxygen therapy (HBOT), bevacizumab, pentoxifylline, vitamin E, laser-induced thermal therapy and/or surgery. [6][7][8][9][10] A recent Cochrane systematic review showed paucity of data on the topic, and was only able to include three comparative studies that used bevacizumab, edaravone and vitamin E. 11 HBOT is a non-invasive treatment that may stabilise necrosis, promote tissue repair and expedite neurological recovery. 12,13 Small retrospective studies have demonstrated high rates of benefit with either rates of stability or improvement estimated at 70%-80% of treated patients.…”