Avastin for radiation necrosis – pro

Avastin is an anti-angiogenic agent and a natural candidate for blocking vascular endothelial growth factor (VEGF) that produces leaky capillaries which are largely responsible for the edema and symptoms of radiation necrosis in the brain. A number of case reports and series have been published.

Seeing responses in patients treated with bevacizumab for their cancers, led to a placebo-controlled, double-blind, phase II trial sponsored by the U.S. Cancer Therapy Evaluation Program in which bevacizumab would be tested specifically for the treatment of radiation necrosis of the brain.

The trial (Gonzalers et al) was limited to those with progressive symptoms, lower-grade primary brain tumors, and head and neck cancers. All of the patients receiving bevacizumab responded almost immediately to treatment, with regression of necrotic lesions evident on magnetic resonance images, while none of the patients receiving the placebo showed a response. The results were striking, and all of the patients who switched from placebo showed a response to bevacizumab as well. So far, responses have persisted over 6 months even after the end of bevacizumab treatment. However, more studies are clearly needed. A series notes: ” In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.” Another one concluded: “Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.” More recent reports suggest that Avastin is moderately effective in reducing radiation necrosis.

A recent reviews by Lubeiski concluded that 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.

Wong ET, Huberman M, Lu XQ, Mahadevan A.Bevacizumab reverses cerebral radiation necrosis.J Clin Oncol. 2008 Dec 1;26(34):5649-50.

Liu AK, Macy ME, Foreman NK. Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys. Nov 15 2009;75(4):1148-54.

Barajas RF Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology. Nov 2009;253(2):486-96.

Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. Apr 1 2011;79(5):1487-95.

Plimpton SR, Stence N, Hemenway M, Hankinson TC, Foreman N, Liu AK. Cerebral Radiation Necrosis in Pediatric Patients. Pediatr Hematol Oncol. May 7 2013

Torcuator R, Zuniga R, Mohan YS, Rock J, Doyle T, Anderson J, Gutierrez J, Ryu S, Jain R, Rosenblum M, Mikkelsen T.Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol. 2009 Aug;94(1):63-8.

Gonzalez J, Kumar AJ, Conrad CA, Levin VA.
Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):323-6.

Liu AK, Macy ME, Foreman NK.Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas.Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1148-54

Sadraei NH1, Dahiya S, Chao ST, Murphy ES, Osei-Boateng K, Xie H, Suh JH, Peereboom DM, Stevens GH, Ahluwalia MS.
Treatment of cerebral radiation necrosis with bevacizumab: the Cleveland clinic experience.Am J Clin Oncol. 2015 Jun;38(3):304-10.

Lubelski D1, Abdullah KG, Weil RJ, Marko NF.Bevacizumab for radiation necrosis following treatment of high grade glioma: a systematic review of the literature.J Neurooncol. 2013 Dec;115(3):317-22.


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