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PLOS ONE  2013 

Bevacizumab Treatment for Meningiomas in NF2: A Retrospective Analysis of 15 Patients

DOI: 10.1371/journal.pone.0059941

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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.

References

[1]  CBTRUS (2012 March) CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004?22008.
[2]  Bria C, Wegner RE, Clump DA, Vargo JA, Mintz AH, et al. (2011) Fractionated stereotactic radiosurgery for the treatment of meningiomas. J Cancer Res Ther 7: 52–57.
[3]  Norden AD, Drappatz J, Wen PY (2009) Advances in meningioma therapy. Curr Neurol Neurosci Rep 9: 231–240.
[4]  Smith MJ, Higgs JE, Bowers NL, Halliday D, Paterson J, et al. (2011) Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset. J Med Genet 48: 261–265.
[5]  Baser ME, Friedman JM, Aeschliman D, Joe H, Wallace AJ, et al. (2002) Predictors of the risk of mortality in neurofibromatosis 2. Am J Hum Genet 71: 715–723.
[6]  Nunes F, MacCollin M (2003) Neurofibromatosis 2 in the pediatric population. J Child Neurol 18: 718–724.
[7]  Rosen LS (2002) Clinical experience with angiogenesis signaling inhibitors: focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control 9: 36–44.
[8]  Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3: 391–400.
[9]  Plotkin SR, Stemmer-Rachamimov AO, Barker FG, Halpin C, Padera TP, et al. (2009) Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 361: 358–367.
[10]  Goutagny S, Raymond E, Sterkers O, Colombani JM, Kalamarides M (2011) Radiographic regression of cranial meningioma in a NF2 patient treated by bevacizumab. Ann Oncol 22: 990–991.
[11]  Puchner MJ, Hans VH, Harati A, Lohmann F, Glas M, et al. (2010) Bevacizumab-induced regression of anaplastic meningioma. Ann Oncol 21: 2445–2446.
[12]  Lou E, Sumrall AL, Turner S, Peters KB, Desjardins A, et al. (2012) Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series. J Neurooncol 109: 63–70.
[13]  Nayak L, Iwamoto FM, Rudnick JD, Norden AD, Lee EQ, et al. (2012) Atypical and anaplastic meningiomas treated with bevacizumab. J Neurooncol 109: 187–193.
[14]  Goodwin JW, Crowley J, Eyre HJ, Stafford B, Jaeckle KA, et al. (1993) A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study. J Neurooncol 15: 75–77.
[15]  Chamberlain MC, Tsao-Wei DD, Groshen S (2006) Salvage chemotherapy with CPT-11 for recurrent meningioma. J Neurooncol 78: 271–276.
[16]  Chamberlain MC, Tsao-Wei DD, Groshen S (2004) Temozolomide for treatment-resistant recurrent meningioma. Neurology 62: 1210–1212.
[17]  Johnson DR, Kimmel DW, Burch PA, Cascino TL, Giannini C, et al. (2011) Phase II study of subcutaneous octreotide in adults with recurrent or progressive meningioma and meningeal hemangiopericytoma. Neuro Oncol 13: 530–535.
[18]  Schulz C, Mathieu R, Kunz U, Mauer UM (2011) Treatment of unresectable skull base meningiomas with somatostatin analogs. Neurosurg Focus 30: E11.
[19]  Grunberg SM, Weiss MH, Russell CA, Spitz IM, Ahmadi J, et al. (2006) Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma. Cancer Invest 24: 727–733.
[20]  Norden AD, Raizer JJ, Abrey LE, Lamborn KR, Lassman AB, et al.. (2009) Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol.
[21]  Wen PY, Yung WK, Lamborn KR, Norden AD, Cloughesy TF, et al. (2009) Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01?08). Neuro Oncol 11: 853–860.
[22]  Chamberlain MC, Glantz MJ (2008) Interferon-alpha for recurrent World Health Organization grade 1 intracranial meningiomas. Cancer 113: 2146–2151.
[23]  Kaba SE, DeMonte F, Bruner JM, Kyritsis AP, Jaeckle KA, et al. (1997) The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B. Neurosurgery 40: 271–275.
[24]  Schrell UM, Rittig MG, Anders M, Koch UH, Marschalek R, et al. (1997) Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea. J Neurosurg 86: 840–844.
[25]  Loven D, Hardoff R, Sever ZB, Steinmetz AP, Gornish M, et al. (2004) Non-resectable slow-growing meningiomas treated by hydroxyurea. J Neurooncol 67: 221–226.
[26]  Mason WP, Gentili F, Macdonald DR, Hariharan S, Cruz CR, et al. (2002) Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma. J Neurosurg 97: 341–346.
[27]  Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, et al. (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45: 228–247.
[28]  Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ, et al. (2012) Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol 33: 1046–1052.

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