Establishment of nomograms for the prediction of useful hearing loss in patients with neurofibromatosis type 2

PURPOSE Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.

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Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas

Cancers ◽

10.3390/cancers12092355 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2355

Author(s):

Isabel Gugel ◽

Florian Grimm ◽

Julian Zipfel ◽

Christian Teuber ◽

Ulrike Ernemann ◽

...

Keyword(s):

Hearing Loss ◽

Clinical Course ◽

Age At Onset ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Speech Discrimination ◽

Predictive Values ◽

Presenting Symptoms

The presenting symptoms of the tumor suppressor gene syndrome neurofibromatosis type 2 (NF2) are often non-specific and unrelated to the disease hallmark bilateral vestibular schwannomas (VS). However, age at onset and presenting symptoms may have predictive values for the clinical course of VS. In this retrospective single-center study, we addressed this issue by reviewing 106 patients with 194 VS. Presenting symptoms attributable to VS commonly occur in 87% of adults and 31% of children. Age at onset significantly correlates with tumor volumes at presentation (p = 0.034). In addition, age at onset significantly correlates with pure-tone average (p = 0.0001), speech discrimination scores (p = 0.001), age at beginning of hearing loss (p = 0.0001), age at deafness (p = 0.0001), and age at first surgery (p = 0.0001). Patients presenting with VS related symptoms had significantly (p < 0.05) worse hearing values at presentation and after surgery. These patients also exhibited higher growth rates and tumor volumes compared to patients with non-VS related presenting symptoms, but this difference did not reach the significance level of p < 0.05. Due to the late appearance of these symptoms, the time of beginning hearing loss, surgery and deafness is significantly delayed (p < 0.05) compared to patients not presenting with VS. In summary, age at onset and type of presenting symptom provide excellent prognostic parameters for predicting VS- and hearing-related clinical course.

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Family with neurofibromatosis type 2 and autosomal dominant hearing loss: identification of carriers of the mutated NF2 gene

Human Genetics ◽

10.1007/bf00214177 ◽

1995 ◽

Vol 96 (1) ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

E. K. Bijlsma ◽

P. Merel ◽

P. Fleury ◽

C. J. van Asperen ◽

A. Westerveld ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Dominant ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Nf2 Gene

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Internal Auditory Canal Decompression for Hearing Maintenance in Neurofibromatosis Type 2 Patients

Neurosurgery ◽

10.1227/neu.0000000000001125 ◽

2015 ◽

Vol 79 (3) ◽

pp. 370-377 ◽

Cited By ~ 7

Author(s):

Daniele Bernardeschi ◽

Matthieu Peyre ◽

Michael Collin ◽

Mustapha Smail ◽

Olivier Sterkers ◽

...

Keyword(s):

Hearing Loss ◽

Internal Auditory Canal ◽

Neurofibromatosis Type ◽

Early Postoperative Period ◽

Neurofibromatosis Type 2 ◽

Hearing Level ◽

Speech Discrimination ◽

Unilateral Deafness

Abstract BACKGROUND: In neurofibromatosis type 2 (NF2), multiple therapeutic options are available to prevent bilateral hearing loss that significantly affects the quality of life of patients. OBJECTIVE: To evaluate the morbidity and functional results of internal auditory canal (IAC) decompression in NF2 patients with an only hearing ear. METHODS: Twenty-one NF2 patients operated on for IAC decompression in a 3-year period with a minimum follow-up of 1 year were included in this retrospective study. They presented unilateral deafness due to previous contralateral vestibular schwannoma removal in 16 patients or contralateral hearing loss due to the tumor in 5 patients. Hearing level was of class A (American Academy of Otolaryngology-Head and Neck Surgery classification) in 7 patients, B in 8 patients, C in 1 patient, and D in 5 patients. Pure-tone average and speech discrimination score evaluations were performed at 6 days, 1 year, and during the follow-up. Eight patients had postoperative chemotherapy. RESULTS: No case of facial nerve palsy was observed. In the early postoperative period; all patients maintained the hearing class of the preoperative period. At 1-year follow-up, all but 3 patients maintained their hearing scores; at last follow-up (mean follow-up, 23 + 8 months; range, 12-44 months), hearing classes remained stable with only 1 patient worsening from class B to C and 1 patient improving from class D to B. CONCLUSION: Decompression of IAC seems to be a useful procedure for hearing maintenance in NF2 patients, with very low morbidity. Ideal timing and association with chemotherapy should be evaluated in the future.

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