title: Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15 patients.
abstract: Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined. To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.
authors.affiliation: Neurology Department, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Fabio P
authors.initials: FP
authors.lastname: Nunes
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Merker
authors.forename: Dominique
authors.initials: D
authors.lastname: Jennings
authors.forename: Paul A
authors.initials: PA
authors.lastname: Caruso
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: di Tomaso
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Fred G
authors.initials: FG
authors.lastname: Barker
authors.forename: Anat
authors.initials: A
authors.lastname: Stemmer-Rachamimov
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
mesh_terms: D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008579:Meningioma / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D016518:Neurofibromatosis 2 / Q000150:complications*; D009464:Neuroma, Acoustic / Q000188:drug therapy; D012044:Regression Analysis; D012189:Retrospective Studies; D012984:Software; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
references.citation: Cancer. 2008 Oct 15;113(8):2146-51
references.pmid: 18756531
references.citation: J Neurooncol. 2004 Mar-Apr;67(1-2):221-6
references.pmid: 15072471
references.citation: Neurology. 2004 Apr 13;62(7):1210-2
references.pmid: 15079029
references.citation: J Neurooncol. 2012 Aug;109(1):187-93
references.pmid: 22544653
references.citation: Cancer Invest. 2006 Dec;24(8):727-33
references.pmid: 17162554
references.citation: J Child Neurol. 2003 Oct;18(10):718-24
references.pmid: 14649556
references.citation: J Neurosurg. 2002 Aug;97(2):341-6
references.pmid: 12186462
references.citation: Ann Oncol. 2010 Dec;21(12):2445-2446
references.pmid: 21041375
references.citation: Nat Rev Drug Discov. 2004 May;3(5):391-400
references.pmid: 15136787
references.citation: Neurosurgery. 1997 Feb;40(2):271-5
references.pmid: 9007858
references.citation: Curr Neurol Neurosci Rep. 2009 May;9(3):231-40
references.pmid: 19348712
references.citation: Eur J Cancer. 2009 Jan;45(2):228-47
references.pmid: 19097774
references.citation: J Cancer Res Ther. 2011 Jan-Mar;7(1):52-7
references.pmid: 21546743
references.citation: Otol Neurotol. 2012 Aug;33(6):1046-52
references.pmid: 22805104
references.citation: Neuro Oncol. 2011 May;13(5):530-5
references.pmid: 21558077
references.citation: Neurosurg Focus. 2011 May;30(5):E11
references.pmid: 21529167
references.citation: J Neurooncol. 1993 Jan;15(1):75-7
references.pmid: 8455065
references.citation: Cancer Control. 2002 Mar-Apr;9(2 Suppl):36-44
references.pmid: 11965229
references.citation: Am J Hum Genet. 2002 Oct;71(4):715-23
references.pmid: 12235555
references.citation: J Neurooncol. 2012 Aug;109(1):63-70
references.pmid: 22535433
references.citation: J Neurooncol. 2010 Jan;96(2):211-7
references.pmid: 19562255
references.citation: J Med Genet. 2011 Apr;48(4):261-5
references.pmid: 21278391
references.citation: J Neurooncol. 2006 Jul;78(3):271-6
references.pmid: 16628476
references.citation: J Neurosurg. 1997 May;86(5):840-4
references.pmid: 9126900
references.citation: Neuro Oncol. 2009 Dec;11(6):853-60
references.pmid: 19293394
references.citation: N Engl J Med. 2009 Jul 23;361(4):358-67
references.pmid: 19587327
references.citation: Ann Oncol. 2011 Apr;22(4):990-991
references.pmid: 21357650