Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis

Yonezawa, Suguru; Miwa, Kazuhiro; Shinoda, Jun; Nomura, Yuichi; Asano, Yoshitaka; Nakayama, Noriyuki; Ohe, Naoyuki; Yano, Hirohito; Iwama, Toru

doi:10.1007/s11060-014-1453-y

Cited by 32 publications

(71 citation statements)

References 34 publications

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“…20–25 We feel that our previous data for the treatment of 27 patients with BRN 15 are sufficient and appropriate as a reference for the treatment response rate. The present study revealed a 79% response to bevacizumab that is similar to other reports of bevacizumab in BRN 3–5,16–19 and is also much better compared with our prior study's 15% response rate. 15 …”

Section: Discussionsupporting

confidence: 89%

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A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†

Furuse

Nonoguchi

Kuroiwa

et al. 2016

Neuro-Oncology Practice

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BackgroundBrain radiation necrosis (BRN) can be a complication of radiotherapy for primary and secondary brain tumors, as well as head and neck tumors. Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN.MethodsPatients with surgically untreatable, symptomatic BRN refractory to conventional medical treatments (eg, corticosteroid, anticoagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilesional edema with a lesion-to-normal brain ratio ≤1.8 on 11C-methionine or ≤2.5 on 18F-boronophenylalanine PET was BRN, not tumor recurrence, and 6 cycles of biweekly bevacizumab (5 mg/kg) were administered. The primary endpoint was a ≥30% reduction from the patients' registration for perilesional edema continuing for ≥1 month.ResultsOf the 41 patients enrolled, 38 were fully eligible for the response assessment. The primary endpoint was achieved in 30 of the 38 (78.9%) patients at 3.0 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of their Karnofsy Performance Score. Corticosteroid use could be reduced in 29 patients (76.3%). Adverse events at grade ≥3 occurred in 10 patients (24.4%).ConclusionsBevacizumab treatment offers certain clinical benefits for patients with surgically untreatable, symptomatic BRN. The determination of BRN using amino-acid PET, not biopsy, is adequate and less invasive for determining eligibility to receive bevacizumab.

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Section: Discussionsupporting

confidence: 89%

“…Although BRN is a well-known, radiation-induced disease, and many reports have been published describing the effect of bevacizumab on BRN, 3–5,16–19 no formal clinical guidelines regarding BRN have been established. Our previous study's findings 15 are thus quoted as the null hypothesis for the treatment response rate.…”

Section: Discussionmentioning

confidence: 99%

A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†

Furuse

Nonoguchi

Kuroiwa

et al. 2016

Neuro-Oncology Practice

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“…However, bevacizumab is an anti-angiogenic drug recognized for its role in pruning vessels and promoting blood supply, which is inconsistent with the above inference [25]. We believe that several mechanisms are [26].Among many previous studies, only a few have reported several recurrence cases [4][5][6][7][8][9][10]. Our literature review shows that previous researchers may have missed progression in many cases reported as "without progression" due to individual differences in bevacizumab sensitivity, short follow-up times after bevacizumab is discontinued, or death shortly after bevacizumab is discontinued.…”

Section: Discussionmentioning

confidence: 80%

“…Compared to previous reports, most studies [4][5][6][7][8][9][10] only reported the efficacy of bevacizumab in the treatment of radiation-induced cerebral necrosis, while there were fewer studies on the recurrence and progression of radiation-induced cerebral necrosis after treatment. No studies have yet explored the reasons for recurrence and progression.…”

Section: Discussionmentioning

confidence: 91%

“…Many clinical studies have shown that bevacizumab produces good shortterm effects on radiation brain necrosis [4][5][6][7][8][9][10][11].However, few studies have reported on radiation brain necrosis progression following bevacizumab discontinuation, and the causes of such progression have not been studied. To provide a reference for clinical treatment, we statistically analyzed bevacizumab treatment efficacy in patients with radiation brain necrosis treated at the Tianjin Cancer Hospital and their progression after bevacizumab discontinuation.…”

Section: Introductionmentioning

confidence: 99%

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Exploration of the Recurrence of Radiation Brain Necrosis After Bevacizumab Discontinuation

Zhuang

Wang

2016

International Journal of Radiation Oncology*Biology*Physics

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Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods:This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible.

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Interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery

Chung

Bryant

Brown

2018

Cochrane Database of Systematic Reviews

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There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.

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Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis

Cited by 32 publications

References 34 publications

A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†

A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†

Exploration of the Recurrence of Radiation Brain Necrosis After Bevacizumab Discontinuation

Interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery

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