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Table of Contents    
COMMENTARY
Year : 2019  |  Volume : 67  |  Issue : 5  |  Page : 1303-1304

Commentary on Safety and Efficacy of Bevacizumab for Radiosurgery-induced Steroid Resistant Brain Edema: Not the Last Part in the Ship of Theseus


Senior Consultant and Oncologist, Apollo Hospital, Chennai, Tamil Nadu, India

Date of Web Publication19-Nov-2019

Correspondence Address:
Dr. T Raja
Senior Consultant and Oncologist, Apollo Hospital, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.271283

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How to cite this article:
Raja T. Commentary on Safety and Efficacy of Bevacizumab for Radiosurgery-induced Steroid Resistant Brain Edema: Not the Last Part in the Ship of Theseus. Neurol India 2019;67:1303-4

How to cite this URL:
Raja T. Commentary on Safety and Efficacy of Bevacizumab for Radiosurgery-induced Steroid Resistant Brain Edema: Not the Last Part in the Ship of Theseus. Neurol India [serial online] 2019 [cited 2019 Dec 7];67:1303-4. Available from: http://www.neurologyindia.com/text.asp?2019/67/5/1303/271283




Radiotherapy, being an inherent treatment modality for many solid tumors, including the brain, has seen technical advancements leading to more advanced conformal techniques of radiation delivery in recent times. However, despite this development, cancer patients have been subjected to suffer from potentially late adverse events which include radiation-induced brain edema and brain necrosis (RIBE and RN)—conditions which are rare in occurrence but have significant clinical and radiological manifestations. Conventional management for these conditions has been to use high-dose corticosteroids, which do have limited efficacy and are laden with significantly strong adverse effects.[1]

Over the past decade, growing evidence have shown benefits of the anti Vascular Endothelial Growth Factor (VEGF) monoclonal antibody bevacizumab in these settings.[2] The current study titled “Bevacizumab for radiosurgery induced brain edema” has evaluated the safety and efficacy of bevacizumab in patients who developed symptomatic edema following Gamma Knife Radio Surgery (GKRS) and who were refractory to corticosteroid therapy. Out of the 17 patients (with clinical and radiological evidence of radiation-induced brain edema) who were retrospectively analyzed in this study, 14 patients (82%) have shown clinical improvement after their 3rd cycle of receiving bevacizumab. Moreover, clinical improvement was elicited well ahead of the radiological evidence of benefit, by a 40-day mean period. This is quite an encouraging result, when compared to the fact that earlier corticosteroids were to be administered for most often, an indefinite period. From this aspect, bevacizumab definitely has a viable advantage from the quality of life, steroid dose requirement, and overall survival points of view.

The scientific rationale behind bevacizumab being used to treat RN and RIBE is the widely accepted vascular mechanism. Radiation causes vascular injury on the surrounding vascular tissue around the tumor. This tissue damage is followed by an oxygen diffusion disorder between the tissue and the vessels, and ultimately tissue hypoxia. This hypoxia causes an increased expression of hypoxia inducible factor 1 α which in turn stimulates VEGF secretion by the astrocytes. Increased VEGF levels yield abnormal neovascularization, and the vessels formed lack a normal vessel structure and exhibit a disordered and fragile structure as well as high permeability, which promotes exudation in the surrounding tissue and brain edema development.[3],[4],[5]

A 100% response rate to bevacizumab was reported by Gonzales et al., in patients with post-radiotherapy RN for malignant gliomas. In a placebo controlled double-blinded randomized trial by Levins et al., which evaluated 114 patients, all bevacizumab-treated patients had experienced a marked improvement in their quality of life.[6],[7]

One must also bear in mind the potential complications of bevacizumab as well which can range from hemorrhage to chances of cerebral infarction. Furthermore, the possibility of recurrence of brain necrosis after bevacizumab is discontinued is also there. Many studies including those by Furuse et al., Boothe et al., and Levins et al. have reported recurrence of brain necrosis after stopping bevacizumab therapy. Bevacizumab reduces new vessel permeability and brain edema, which relieves brain necrosis symptoms, producing a good clinical outcome, addressing the patient's problems and improving quality of life.[8],[9],[10],[11]

The current publication has some limitations in the form of the number of patients evaluated, its retrospective nature, etc. However the outcomes of this study very firmly support the fact that this has to be evaluated in a prospective randomized trial, which will definitely aid in establishing a strong rationale and evidence for adoption and incorporation of this therapy approach into regular clinical practice.



 
  References Top

1.
Tripathi M, Ahuja CK, Mukherjee KK, Kumar N, Dhandapani S, Dutta P, et al. The Safety and Efficacy of Bevacizumab for Radiosurgery-induced steroid-resistant Brain Edema; Not the Last Part in the Ship of Theseus. Neurol India 2019;67:1292-302.  Back to cited text no. 1
  [Full text]  
2.
Zhuang H, Shi S, Yuan Z, Chang JY. Bevacizumab treatment for radiation brain necrosis: Mechanism, efficacy and issues. Mol Cancer 2019;18:21.  Back to cited text no. 2
    
3.
Miyatake S, Nonoguchi N, Furuse M, Yoritsune E, Miyata T, Kawabata S, et al. Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain. Neurol Med Chir (Tokyo) 2015;55(Suppl 1):50-9.  Back to cited text no. 3
    
4.
Kamiryo T, Lopes MB, Kassell NF, Steiner L, Lee KS. Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil. Neurosurgery. 2001;49:409-14 discussion 414-5.  Back to cited text no. 4
    
5.
Nonoguchi N, Miyatake S, Fukumoto M, Furuse M, Hiramatsu R, et al. The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: Pathological consideration of their potential roles. J Neuro-Oncol 2011;105:423-31.  Back to cited text no. 5
    
6.
Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 2007;67:323-6.  Back to cited text no. 6
    
7.
Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, 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 2011;79:1487-95.  Back to cited text no. 7
    
8.
Furuse M, Nonoguchi N, Kawabata S, Yoritsune E, Takahashi M, Inomata T, et al. Bevacizumab treatment for symptomatic radiation necrosis diagnosed by amino acid PET. Jpn J Clin Oncol 2013;43:337-41.  Back to cited text no. 8
    
9.
Boothe D, Young R, Yamada Y, Prager A, Chan T, Beal K. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol 2013;15:1257-63.  Back to cited text no. 9
    
10.
Wang Y, Pan L, Sheng X, Mao Y, Yao Y, Wang E, et al. Reversal of cerebral radiation necrosis with bevacizumab treatment in 17 Chinese patients. Eur J Med Res 2012;17:25.  Back to cited text no. 10
    
11.
Furuse M, Kawabata S, Kuroiwa T, Miyatake S. Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: A report of 2 cases. J Neurooncol 2011;102:471-5.  Back to cited text no. 11
    




 

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