Bevacizumab Treatment for Patients with NF2-Related Schwannomatosis: A Single Center Experience

Abstract

(1) Background: NF2-related schwannomatosis, characterized by the development of bilateral vestibular schwannomas, often necessitates varied treatment approaches. Bevacizumab, though widely utilized, demonstrates variable effectiveness on hearing and tumor growth. At the same time, (serious) adverse events have been frequently reported. (2) Methods: A single center retrospective study was conducted, on NF2-related schwannomatosis patients treated with bevacizumab from 2013 to 2023, with the aim to assess treatment-related and clinical outcomes. Outcomes of interest comprised hearing, radiologic response, symptoms, and adverse events. (3) Results: Seventeen patients received 7.5 mg/kg bevacizumab for 7.1 months. Following treatment, 40% of the patients experienced hearing improvement, 53%, stable hearing, and 7%, hearing loss. Vestibular schwannoma regression occurred in 31%, and 69% remained stable. Further symptomatic improvement was reported by 41%, stable symptoms by 47%, and worsened symptoms by 12%. Treatment discontinuation due to adverse events was observed in 29% of cases. Hypertension (82%) and fatigue (29%) were most frequently reported, with no occurrences of grade 4/5 toxicities. (4) Conclusion: Supporting previous studies, bevacizumab demonstrated positive effects on hearing, tumor control, and symptoms in NF2-related schwannomatosis, albeit with common adverse events. Therefore, careful consideration of an appropriate management strategy is warranted.

Keywords: acoustic neuroma; adverse events; bevacizumab; cerebellopontine angle tumor; hearing; neurofibromatosis type 2; schwannomatosis; tumor response; vestibular schwannoma.

Figure 1

Treatment regimens and response of individual patients in the cohort. Duration and dosage of treatment is indicated by bar length and coloring, respectively. At the end of each treatment course, hearing, radiologic, and symptomatic response were recorded. Symbols indicate the outcome of interest, coloring indicates an improved, stable, or worsened response. Four patients received more than one bevacizumab treatment course. Time interval between consecutive treatments corresponds to the white area between the horizontal bars.

Figure 2

Change in maximum word recognition score (WRS) after treatment with bevacizumab. Patients are represented on the horizontal axis. Individual WRS before and after bevacizumab are stated above and below the arrows. Percentage change in WRS is represented by the length of the arrow, with the direction representing hearing improvement or loss. Six patients (40%) experienced improved hearing, eight patients (53%) had stable hearing, and one patient (7%) experienced hearing loss. Three patients (patients 2, 9, and 12) already had maximum speech recognition at the start of treatment.

Figure 3

Change in absolute extracanicular volume (cm³) of vestibular schwannomas after bevacizumab treatment. Vertical bars represent the target vestibular schwannoma of a patient. Coloring of the bars indicate the corresponding tumor response: green for tumor regression (volume change ≥20%), yellow for stable tumor (volume change between −20% and 20%). Three target vestibular schwannomas are not shown: one tumor was confined to the internal auditory canal, two other tumors were not followed up with MRI at the end of treatment.