Bevacizumab Treatment for Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Yoritsune, Erina; Takahashi, Masatsugu; Inomata, Taisuke; Kuroiwa, Toshihiko; Miyatake, Shin‐Ichi

doi:10.1093/jjco/hys231

Cited by 35 publications

(66 citation statements)

References 12 publications

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“…Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, 1 bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN. 2–6 However, bevacizumab's optimal dose, dosing interval, and duration of efficacy have not been fully defined.…”

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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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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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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: 70%

“…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: 88%

“…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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“…The use of bevacizumab has been reported to improve neurological symptoms and signal alterations in MRI of cerebral necrosis in adults and 4 children [1,8,9,10] treated for malignant tumors. A phase I trial with 14 patients suggested positive effects on cerebral radiation necrosis [1].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Bevacizumab for Radiation-Induced Cerebral Necrosis in Children

Preuß

Hirsch²,

Hoffmann³

et al. 2013

Pediatr Neurosurg

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Introduction: Bevacizumab has been reported to effectively reduce cerebral edema caused by radiation therapy. However, only limited data with a short follow-up in tumor patients are available so far. Patients and Methods: Two children suffering from hemorrhage from arteriovenous malformation (AVM) have been treated with stereotactic radiotherapy and developed radiation-induced cerebral edema with deteriorating neurological status despite maximized steroid therapy. Bevacizumab administration at 5 mg/kg body weight was initiated every 2 weeks. Results: Bevacizumab treatment rapidly ameliorated the neurological deficits, malignant edema and prevented catastrophic complications. Corticoid therapy could be reduced and discontinued. However, after 18 months, both patients showed identical or worse neurological status than before bevacizumab therapy. AVM radiation therapy had been successful to completely obliterate AVMs. Discussion: In our limited experience, bevacizumab may be an effective and safe option for rescue therapy for malignant cerebral edema on the basis of radiation-induced necrosis especially in patients who experience rapid deterioration despite corticoid therapy and/or intolerable steroid side effects. Despite the fact that functional improvement could not be achieved in long-term outcome patients significantly stabilized and improved during periods of acute deterioration. In order to determine the long-term effectiveness of bevacizumab further investigation in placebo-controlled studies with a higher number of patients are required.

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Bevacizumab Treatment for Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET

Cited by 35 publications

References 12 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

Effectiveness of Bevacizumab for Radiation-Induced Cerebral Necrosis in Children

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