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Year : 2015  |  Volume : 11  |  Issue : 2  |  Page : 485-487

Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases

1 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China
2 Department of Neurology, Chinese People's Liberation Army, Wuhan General Hospital, Wuhan, China

Date of Web Publication7-Jul-2015

Correspondence Address:
Hu Wei-Guo
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan
Song Qi-Bin
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.140782

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 > Abstract 

To analyze the therapeutic effect of bevacizumab on radiation-induced brain necrosis. Four radiation-induced brain necrosis patients, administered with bevacizumab at a dose of 7.5 mg/kg every 3 weeks, 2 times. One case of brain metastasis of lung cancer and one case of nasopharyngeal carcinoma with brain necrosis after radiotherapy. However, their physical signs disappeared after the treatment with bevacizumab. One case of brainstem lesion and one case of brain glioma patient showed a transient improvement in signs and symptoms after treatment with bevacizumab. Bevacizumab can significantly alleviate the radiation-induced brain edema, and can improve the symptoms successively.

Keywords: Bevacizumab, brain necrosis, radiation

How to cite this article:
Xiang-Pan L, Yuxin C, Xiao-Fei W, Na L, Tang-Peng X, Xiao-Tao X, Chang-Li R, Wei-Guo H, Qi-Bin S. Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases. J Can Res Ther 2015;11:485-7

How to cite this URL:
Xiang-Pan L, Yuxin C, Xiao-Fei W, Na L, Tang-Peng X, Xiao-Tao X, Chang-Li R, Wei-Guo H, Qi-Bin S. Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases. J Can Res Ther [serial online] 2015 [cited 2020 May 27];11:485-7. Available from: http://www.cancerjournal.net/text.asp?2015/11/2/485/140782

 > Introduction Top

Radiation induced brain necrosis (RN) is an intractable iatrogenic disease. [1] RN constitutes a continuous process in which endothelial cell dysfunction leads to tissue hypoxia and necrosis, with the concomitant release of vasoactive compounds such as vascular endothelial growth factor (VEGF). [2] Bevacizumab has been suggested as a new treatment for cerebral radiation necrosis. [3],[4] However, there remains controversy pertaining to the efficacy of this treatment, whereas some researchers claim that treatment with bevacizumab reverses cerebral radiation necrosis effectively, [5] others claim that such treatment increases the risk of over-pruning blood vessels that could potentially exacerbate cerebral radiation necrosis. [6] In this report we further investigated both the clinical and nuclear magnetic resonance imaging (MRI) responses of treatment with bevacizumab in four patients with brain edema induced by radiotherapy.

 > Case report Top

Four cerebral necrosis patients, manifesting no improvement upon treatment with dexamethasone, were selected for treatment with bevacizumab. All data were prospectively recorded and analyzed.

Bevacizumab therapy was administered for two cycles (7.5 mg/kg, at 3-week intervals).

Case 1

60-year-old woman, whose PET-CT and MRI revealed solitary metastases in the left temporal lobe in November 2010. In May 2011, she received whole brain radiotherapy, followed by an additional X-knife radiation. In May 2012, she experienced memory loss, together with weakness and mild imbalance, cranial MRI and magnetic resonance spectrum indicated brain necrosis and large perilesional edema. Administration with dexamethasone and mannitol improved her symptoms, however, the symptoms relapsed after these drugs were discontinued. She received bevacizumab 500 mg twice. Unexpectedly, her memory loss improved remarkably, her weakness restored to normaland previous symptoms of headache, nausea, and vomit disappeared. MRI demonstrated typical changes before and after treatment with bevacizumab [Figure 1].
Figure 1: The 4 pictures above display MRI images with contrast before treatment of bevacizumab, while the 4 pictures below demonstrate MRI images with contrast after treatment of bevacizumab. Before bevacizumab administration, T1-weighted MR revealed rosette shaped folds of necrotic lesions, T2-weighted MR revealed large perilesional edema. 3 weeks after treatment with bevacizumab, MRI showed decreased lesion of necrosis in the left temporal lobe, postcontrast enhanced lesion indistinct, while the edema shrank obviously

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Case 2

8-year-old girl presented with nasal staring of both eyes and walk imbalance. On March 17, 2012, her cranial MRI revealed a brainstem lesion and perilesional edema. On April 9, 2012, she received radiotherapy of brainstem: 50Gy/2Gy/25f, and concurrent chemotherapy with temozolomide. In October 2012, her cranial MRI revealed enlarged lesion. During the period from November to December 2012, she was treated with 150 mg bevacizumab twice. Then her dizziness and limb movement disorder improved quickly. On January 9, 2013, cranial MRI revealed enlarged brainstem lesion and mild improvement of the edema. On February 16, 2013, she presented totally blind, fever, brain hernia, and died. Changes of the brain edema lesions were detected by MRI, displayed in [Figure 2].
Figure 2: Five months after radiotherapy, cranial MRI revealed enlarged lesion as well as perilesional edema. Treated with 150 mg bevacizumab twice, and 3 weeks later, her cranial MRI revealed: T1 weighted MR post gadolinium brainstem lesion enlarged, T2-weighted MR perilesional edema barely improved

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Case 3

44-year-old woman, her cranial MRI showed: Rear left temporo parietal and parietal lobe presented 2 patchy lesions, about 2.5mm in diameter. On June 12, 2012, she received neurosurgical resection of the left temporal lesions (parietal lesions preserved). Post-operational pathological examination indicated: Graded astrocytoma WHO grade 3. On July 2, 2012, she received radiotherapy, concurrent chemotherapy with temozolomide. On October 15, 2012, her lower extremity weakness progressively aggravated. She was treated with diuretic and cortisone drugs, which had cured those symptoms. In November 2012, she presented lower extremity weakness and slurred speech. On November 13, 2012 and December 4, 2012, she received 500 mg bevacizumab twice. Then her muscle force restored, and her speech recovered. On March 20, 2013, cranial MRI revealed a possibility of glioma relapse. On March 25, 2013, a 5 Χ 6 cm tumor was surgically removed from her left frontal and parietal lobe. Post-operational biopsy demonstrated astrocytoma, WHO class 3. In May 2013, her cranial MRI did not reveal distinct tumor relapse or edema [Figure 3].
Figure 3: Before bevacizumab administration, T1 weighted MR post gadolinium demonstrated rosette-shaped folds of lesions, T2-weighted MR showed perilesional edema, midline slightly skewed to the right. Four months later, after administration of 500 mg bevacizumab twice, MRI revealed enlarged lesion, enhancement, and expanded edema

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Case 4

A 59-year-old Chinese woman definitely diagnosed with nasopharyngeal squamous cell carcinoma in 2008, received 2-dimentional radiotherapy: 76Gy/2Gy/38f. In March 2013, she lost consciousness during exercise. Her cranial MRI revealed bilateral temporal lobe necrosis and large perilesional edema, correspondent with previous irradiated site. Mini-mental state examination (MMSE) scored 24 grades. On July 15 and August 7, 2013, she was treated with 400 mg bevacizumab twice. On September 1, 2013, her cranial MRI revealed brain necrosis and perilesional edema shrank significantly. MMSE scored 26. Changes of the brain lesions were displayed on MRI [Figure 4].
Figure 4: The 4 images above indicate, T1 weighted MR post gadolinium revealed bilateral temporal lobe necrosis and rosette shaped lesions, T2-weighted MR revealed large perilesional edema. The 4 pictures below indicate, after administration of 400 mg bevacizumab twice, 3 weeks later, skull enhanced MRI revealed: T1- weighted MR showed shrunken brain necrosis, T2-weighted MR also showed distinct shrunken perilesional edema

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 > Discussion Top

RN is a serious late complication of radiation therapy (RT) for brain tumors which develops 6 months to 3 years after completion of RT. [7] Common symptoms include psychomotor slowing, seizures, sensorimotor de[TAG:2][/TAG:2]

cits, and language impairment. [7],[8] Volume of irradiated area and total radiation dose are the most predictive factors for RN. [9],[10]

Bevacizumab, an anti-VEGF antibody, has been proposed as treatment for RN. The potential beneficial effects of treatment with bevacizumab on radiation necrosis were first reported by Gonzalez et al., [11] in a retrospective analysis published in 2007 in which all eight patients treated with bevacizumab showed radiographic improvement with an average of 44% reduction in gadolinium-enhanced MRI studies and 59.75% reduction in FLAIR MRI studies. In 2011, Levin et al. [4] conducted a randomized double-blind placebo-controlled trial of treatment with bevacizumab in 14 patients with radiation necrosis. They showed a mean percentage change in RN volume on T1 post-contrast and FLAIR studies as 59% and 63%, respectively. There were two phase studies about bevacizumab alleviating radiation necrosis, the NCT01621880 trail aimed to compare 4 course of bevacizumab with methylprednisolone in patients with radiation-induced brain necrosis of nasopharyngeal carcinoma, it has been completed in China in December 2013; the NCT01201850 trail is the ongoing clinical trial in Children's Hospital Colorado, to explore the role of bevacizumab in the treatment of radiation necrosis in children with central nervous system tumors.

Comparatively, in our study, bevacizumab has been shown to alleviate neuro-cognitive deficits and cerebral edema. As is shown in case 1 and case 4, significant clinical improvements were observed according to MRI imaging. As for case 1, administration of bevacizumab 500 mg twice has sufficiently improved her memory loss, and reversed her lower extremity weakness. As for case 4, 400 mg bevacizumab administered twice has helped to elevate MMSE. Case 3 was a recurrent glioma, 500 mg bevacizumab given twice didn't seem to improve the symptoms remarkably. Case 2 was an uncontrolled brainstem glioma, bevacizumab to a certain extent it ameliorated her dizziness, limb movement disorder, but the uncontrolled glioma still progressed, and ultimately lead to the death of the patient.

Our results indicate that bevacizumab may become a promising drug for alleviating cerebral necrosis. Bevacizumab can significantly alleviate the radiation-induced brain edema, and can improve the symptoms successively, but for the uncontrollable cancer, bevacizumab only relieved the symptom for a short term, hence the symptoms may relapse. Thus we may speculate that bevacizumab is possibly more advisable to reverse brain necrosis of locally controlled cancers.

 > References Top

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. 1
Narita Y. Drug review: Safety and efficacy of bevacizumab for glioblastoma and other brain tumors. Jpn J Clin Oncol 2013;43:587-95.  Back to cited text no. 2
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. 3
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. 4
Wong ET, Huberman M, Lu XQ, Mahadevan A. Bevacizumab reverses cerebral radiation necrosis. J Clin Oncol 2008;26:5649-50.  Back to cited text no. 5
Jeyaretna DS, Curry WT Jr, Batchelor TT, Stemmer-Rachamimov A, Plotkin SR. Exacerbation of cerebral radiation necrosis by bevacizumab. J Clin Oncol 2011;29:e159-62.  Back to cited text no. 6
Giglio P, Gilbert MR. Cerebral radiation necrosis. Neurologist 2003;9:180-8.  Back to cited text no. 7
Butler JM, Rapp SR, Shaw EG. Managing the cognitive effects of brain tumor radiation therapy. Curr Treat Options Oncol 2006;7:517-23.  Back to cited text no. 8
Marks JE, Baglan RJ, Prassad SC, Blank WF. Cerebral radionecrosis: Incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 1981;7:243-52.  Back to cited text no. 9
Sadraei NH, Dahiya S, Chao ST, Murphy ES, Osei-Boateng K, Xie H, et al. Treatment of cerebral radiation necrosis with bevacizumab: The Cleveland Clinic Experience. Am J Clin Oncol 2013.  Back to cited text no. 10
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. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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