Long-Term Effects of Bevacizumab on Vestibular Schwannoma Volume in Neurofibromatosis Type 2 Patients

Abstract

Introduction Bevacizumab offers a medical treatment that may slow the growth of vestibular schwannomas (VS) and possibly preserve hearing in patients with neurofibromatosis type 2 (NF2). This study aims to investigate the effect of long-term bevacizumab treatment on VS progression.

Methods Demographic, clinical, audiometric, and radiographic data were collected from the medical records of NF2 patients treated with bevacizumab at a tertiary medical center.

Results Eleven tumors from seven NF2 patients treated with bevacizumab were analyzed. The median age was 17 years (range: 12–47 years). Median bevacizumab treatment time was 33 months (range: 12–74 months). Of five patients with serviceable hearing pretreatment, one (20%) maintained serviceable hearing during bevacizumab therapy. Significantly slower growth rates for both tumor diameters and tumor volumes were identified during active bevacizumab treatment. Median tumor diameters and volumes during active bevacizumab treatment were 0 cm/year (range: –0.13–0.17 cm/year) and 0.1 cm³/year (range: –0.92–0.41), compared with 0.37 cm/year (range: 0–1.5 cm/year, p = 0.0011) and 1.38 cm³/year (range: 0.013–3.74), respectively, without bevacizumab treatment (p = 0.0263). Reduced tumor progression was noted with bevacizumab treatment utilizing both linear greatest diameter (hazard ratio 0.16, p = 0.006) and segmentation volumes (hazard ratio 0.15, p = 0.023). Complications of bevacizumab treatment included fatigue (43%), nausea/vomiting (43%), hypertension (43%), epistaxis (29%), and proteinuria (29%). One subject had a cerebrovascular accident detected on screening magnetic resonance imaging without symptoms or neurological sequelae.

Discussion Bevacizumab may reduce tumor growth rate and the risk of progression based on both volumetric and linear measurements.

Keywords

vestibular schwannoma - neurofibromatosis type 2 - bevacizumab - Avastin - acoustic neuroma

IRB

This project was approved and in compliance with University of Texas Southwestern Medical Center IRB (122016–038).

Authorship Participation

Study design: Killeen, Tolisano, Hunter, Kutz

Data acquisition: Killeen, Hunter

Data Analysis: Killeen, Tolisano, Hunter, Kutz

Manuscript drafting: Killeen, Tolisano, Hunter, Kutz

Critical Revisions: Killeen, Klesse, Tolisano, Hunter, Kutz

• References

• 1 Evans JA, Vitez M, Czeizel A. Patterns of acrorenal malformation associations. Am J Med Genet 1992; 44 (04) 413-419
• 2 Slattery WH. Neurofibromatosis type 2. Otolaryngol Clin North Am 2015; 48 (03) 443-460
• 3 Strasnick B, Glasscock III ME, Haynes D, McMenomey SO, Minor LB. The natural history of untreated acoustic neuromas. Laryngoscope 1994; 104 (09) 1115-1119
• 4 Slattery III WH, Brackmann DE, Hitselberger W. Middle fossa approach for hearing preservation with acoustic neuromas. Am J Otol 1997; 18 (05) 596-601
• 5 Doyle KJ, Shelton C. Hearing preservation in bilateral acoustic neuroma surgery. Am J Otol 1993; 14 (06) 562-565
• 6 Slattery III WH, Brackmann DE, Hitselberger W. Hearing preservation in neurofibromatosis type 2. Am J Otol 1998; 19 (05) 638-643
• 7 Chung LK, Nguyen TP, Sheppard JP. , et al. A systematic review of radiosurgery versus surgery for neurofibromatosis type 2 vestibular schwannomas. World Neurosurg 2018; 109: 47-58
• 8 Plotkin SR, Stemmer-Rachamimov AO, Barker II FG. , et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 2009; 361 (04) 358-367
• 9 Plotkin SR, Merker VL, Halpin C. , et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol 2012; 33 (06) 1046-1052
• 10 Alanin MC, Klausen C, Caye-Thomasen P. , et al. The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2. Eur Arch Otorhinolaryngol 2015; 272 (12) 3627-3633
• 11 Bergsland E, Dickler MN. Maximizing the potential of bevacizumab in cancer treatment. Oncologist 2004; 9 (Suppl. 01) 36-42
• 12 Monsell E, Balkany T, Gates G, Goldenberg RA, Meyerhoff WL, House JW. Committee on hearing and equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). American Academy of Otolaryngology-Head and Neck Surgery Foundation, INC. Otolaryngol Head Neck Surg 1995; 113 (03) 179-180
• 13 Mallory GW, Pollock BE, Foote RL, Carlson ML, Driscoll CL, Link MJ. Stereotactic radiosurgery for neurofibromatosis 2-associated vestibular schwannomas: toward dose optimization for tumor control and functional outcomes. Neurosurgery 2014; 74 (03) 292-300 , discussion 300–301
• 14 Boari N, Bailo M, Gagliardi F. , et al. Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients. J Neurosurg 2014; 121 (Suppl): 123-142
• 15 Kruyt IJ, Verheul JB, Hanssens PEJ, Kunst HPM. Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis type 2: a matched cohort study with sporadic vestibular schwannomas. J Neurosurg 2018; 128 (01) 49-59
• 16 Chen L-H, Zhang H-T, Xu R-X, Zhang L, Li W-D, Sun K. Microsurgery for patients diagnosed with neurofibromatosis type 2 complicated by vestibular schwannomas: clinical experience and strategy for treatments. Medicine (Baltimore) 2018; 97 (17) e0270
• 17 Yamakami I, Ito S, Higuchi Y. Retrosigmoid removal of small acoustic neuroma: curative tumor removal with preservation of function. J Neurosurg 2014; 121 (03) 554-563
• 18 Lloyd SKW, King AT, Rutherford SA. , et al. Hearing optimisation in neurofibromatosis type 2: a systematic review. Clin Otolaryngol 2017; 42 (06) 1329-1337