Bevacizumab treatment for vestibular schwannomas in neurofibromatosis type two: report of two cases, including responses after prior gamma knife and vascular endothelial growth factor inhibition therapy

2011 ◽  
Vol 126 (1) ◽  
pp. 79-82 ◽  
Author(s):  
G K Eminowicz ◽  
R Raman ◽  
J Conibear ◽  
P N Plowman
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Gamma Knife ◽  
Previous History ◽  
Gamma Knife Radiosurgery ◽  
Neurofibromatosis Type ◽  
Vestibular Schwannomas ◽  
Vascular Endothelial ◽  
Bevacizumab Treatment ◽  
Endothelial Growth Factor

AbstractObjectives:Vestibular schwannomas are the hallmark of neurofibromatosis type two. They are difficult to treat, due to their bilateral presentation and the quest for hearing preservation. Our report describes a new treatment approach in this clinical scenario.Case report:We report two cases which confirm that bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, causes regression of vestibular schwannomas in patients with a previous history of gamma knife radiosurgery or failed treatment with another form of vascular endothelial growth factor targeted therapy.Conclusion:In 2009, Plotkin et al. reported the volumetric response of vestibular schwannomas to bevacizumab treatment, both in untreated patients and in patients previously treated with erlotinib, an epidermal growth factor receptor inhibitor. The presented cases support the use of bevacizumab to treat vestibular schwannomas. Given the extremely slow growth of these tumours, we note the rapidity of volume reduction following bevacizumab therapy.

scholarly journals Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2–Associated Vestibular Schwannomas

2016 ◽  
Vol 34 (14) ◽  
pp. 1669-1675 ◽  
Author(s):  
Jaishri O. Blakeley ◽  
Xiaobu Ye ◽  
Dan G. Duda ◽  
Chris F. Halpin ◽  
Amanda L. Bergner ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Hearing Loss ◽  
Growth Factor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Vascular Endothelial ◽  
Bevacizumab Treatment ◽  
Endothelial Growth Factor

Purpose Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs. Patients and Methods Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers. Results Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell–derived factor 1α (P = .037 and .025, respectively). Conclusion Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies.

Endovascular Treatment Increases but Gamma Knife Radiosurgery Decreases Angiogenic Activity of Arteriovenous Malformations

Neurosurgery ◽  
2010 ◽  
Vol 66 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Akin Akakin ◽  
Abdulkadir Ozkan ◽  
Emel Akgun ◽  
Demet Yalcinkaya Koc ◽  
Deniz Konya ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Gamma Knife Radiosurgery ◽  
Vascular Endothelial ◽  
Tissue Samples ◽  
Angiogenic Activity ◽  
Endothelial Growth Factor ◽  
Angiogenesis Model

Abstract OBJECTIVE To compare the angiogenic potentials of embolized, gamma knife–treated or untreated cerebral arteriovenous malformations (AVMs), using a rat cornea angiogenesis model. METHODS Tissue samples from cerebral AVM patients who were either untreated or had previously been treated with embolization or gamma knife radiosurgery and who had undergone operations for hemorrhage at the Neurosurgery Department or the Neurological Sciences Institute of Marmara University were used. For the macroscopic evaluation of angiogenesis, tissue samples were inoculated in a micropocket created on the rat eye, and the level of angiogenic activity was graded macroscopically for 15 days, with glioblastoma multiforme and normal brain artery tissues serving as positive and negative controls, respectively. For the other part of the experiment, eyes of another set of rats were inoculated with the study samples only using the same cornea angiogenesis model, in which microvessel count and vascular endothelial growth factor assessment was done at days 3, 7, 11, and 15. RESULTS Based on our macroscopic findings in the cornea angiogenesis model, embolized AVMs exhibited the highest angiogenic activity, followed by untreated AVMs and gamma knife–treated AVMs. Evaluations of vascular endothelial growth factor expression and microvessel counts showed a similar relation among the 3 tissue groups with regard to the level of angiogenic activity, supporting the results of macroscopic examinations. CONCLUSION This study, for the first time, provides experimental semiquantitative data to compare the angiogenic potentials of embolized and gamma knife–treated AVM tissues. Embolization may increase angiogenic activity, and gamma knife radiosurgery may decrease it when compared with activity in previously untreated AVMs. These data can be useful to understand why recurrence of AVMs after angiographically demonstrated endovascular occlusion is common but after gamma knife occlusion is rare.

Abstract TP445: Bevacizumab Therapy for Brain Arteriovenous Malformations

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Daniel L Cooke ◽  
Helen Kim ◽  
Wade Smith ◽  
Michael Lawton ◽  
Jennifer Clarke ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Arteriovenous Malformations ◽  
Vascular Malformations ◽  
Vascular Endothelial ◽  
Open Label ◽  
Beneficial Effects ◽  
Brain Arteriovenous Malformations ◽  
Bevacizumab Treatment ◽  
Endothelial Growth Factor

Introduction: Brain arteriovenous malformations (bAVM) are dynamic vascular malformations and a significant source of intracranial hemorrhage (ICH). Obliteration by interventional therapy is the only proven method to remove this hemorrhagic risk. Partial bAVM volume reduction using combination therapy does not lessen the risk of future ICH, though such adjuvant treatment is routinely practiced to permit definitive microsurgical resection or radiosurgery. High expression of vascular endothelial growth factor (VEGF) has been reported in bAVM and there is evidence for the beneficial effects of bevacizumab on AVMs from studies using the hereditary hemorrhagic telangiectasia (HHT) bAVM model and in liver AVMs in HHT patients. There is, however, no medical therapy approved to treat bAVMs. The goal of this study is to determine the beneficial effects of the anti-vascular endothelial growth factor drug, Bevacizumab, on bAVM. Hypothesis: Our hypothesis is that bAVM volume will decrease after 12 weeks of bevacizumab treatment. Additionally, we expect that bevacizumab treatment for bAVMs will not increase the occurrence of symptomatic ICH beyond that expected for natural history. Methods: The trial is a 10 patient one-armed, open-label study that will administer bevacizumab (5 mg/kg every 2 weeks) by IV infusion over the course of 12 weeks. The study will assess feasibility, safety, and preliminary evidence of efficacy in bAVMs deemed inoperable by current interventional means. For the purpose of estimating our effect size, we assumed that the bevacizumab treatment effect on bAVM volume will be proportional to the reduction of blood flow measured by the cardiac index in the hepatic AVM-bevacizumab trial. With a sample size of 10 paired observations and a one-tailed α =0.05, we have 84% power to detect a change in bAVM volume of 13%. We will compare pre- and post-treatment (26 weeks) volumes using a paired t-test. Significance: This study is the first medical intervention trial for bAVM. The study will meaningfully impact the clinical and research communities managing AVMs, regardless their anatomic location, and in turn those patients who suffer from them.

Intravitreal Bevacizumab Treatment in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 206-212
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Visual Loss ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Off Label ◽  
Age Related ◽  
Bevacizumab Treatment ◽  
Endothelial Growth Factor

Age-related macular dejeneration is one of the main causes of visual loss in the older population. In recent years, agents developed to aim the inhibition of the vascular endothelial growth factor are the main choice for the treatment of choroidal neovascular membranes often found in the wet type of this disease. This article mentions the standpoint of the off-label used anti-VEGF, bevacizumab, according to the literature.

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