Early Results of Bevacizumab Treatment in Spinal and Peripheral Nerve Schwannomas in Neurofibromatosis Type 2 and Schwannomatosis

Objective Bevacizumab for hearing preservation in patients with neurofibromatosis type 2 (NF2) is an emerging practice. We set out to characterize the effectiveness and toxicity of bevacizumab in our patient group. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Seventeen consecutive patients with NF2 received bevacizumab treatment for vestibular schwannomas, including 2 patients treated to maintain cochlear implant performance. Volumetric analysis of serial magnetic resonance imaging scans was used to evaluate radiographic response, and hearing response was evaluated with serial audiograms. Patient-reported outcomes were also assessed, including subjective hearing improvement, changes in tinnitus, vertigo, headaches, ear pain, and improvement in ability to communicate via telephone. Results A positive radiographic response occurred in 8 of 17 (47%) patients and the median tumor volume change was a tumor decrease of 19%. A positive hearing response was recorded in 5 of 9 (56%) patients. Two patients had a word recognition score improvement over 40%. There was an approximately 40% improvement in patient-reported outcomes. Primary toxicities included hypertension, proteinuria, dysgeusia, and amenorrhea. Conclusion Bevacizumab treatment was followed by hearing improvement in 56% of patients, while decreased tumor volume was noted in 47%. These outcomes agree favorably with prior reported series. There were significant improvements in patient-reported outcomes that have not been described previously.

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Malignant peripheral nerve sheath tumor: Transformation in a patient with neurofibromatosis type 2

Pediatric Blood & Cancer ◽

10.1002/pbc.27520 ◽

2018 ◽

Vol 66 (2) ◽

pp. e27520 ◽

Cited By ~ 1

Author(s):

Laura Agresta ◽

Ralph Salloum ◽

Trent R. Hummel ◽

Nancy Ratner ◽

Francesco T. Mangano ◽

...

Keyword(s):

Peripheral Nerve ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Nerve Sheath Tumor ◽

Peripheral Nerve Sheath Tumor ◽

Nerve Sheath ◽

Tumor Transformation

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Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2

Brain ◽

10.1093/brain/awf115 ◽

2002 ◽

Vol 125 (5) ◽

pp. 996-1004 ◽

Cited By ~ 79

Author(s):

A. D. Sperfeld ◽

C. Hein ◽

J. M. Schröder ◽

A. C. Ludolph ◽

C. O. Hanemann

Keyword(s):

Peripheral Nerve ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Nerve Involvement ◽

Peripheral Nerve Involvement

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Comparison of outcomes of peripheral nerve schwannoma excision in neurofibromatosis type 2 patients and non-neurofibromatosis type 2 patients: A case control study

Journal of Plastic Reconstructive & Aesthetic Surgery ◽

10.1016/j.bjps.2015.05.026 ◽

2015 ◽

Vol 68 (9) ◽

pp. 1199-1203 ◽

Cited By ~ 1

Author(s):

Charlotte L. Bendon ◽

Dominic Furniss ◽

Henk P. Giele

Keyword(s):

Peripheral Nerve ◽

Case Control Study ◽

Neurofibromatosis Type ◽

Case Control ◽

Neurofibromatosis Type 2 ◽

Control Study

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Comparing the sensitivity of linear and volumetric MRI measurements to detect changes in the size of vestibular schwannomas in patients with neurofibromatosis type 2 on bevacizumab treatment

British Journal of Radiology ◽

10.1259/bjr.20160110 ◽

2016 ◽

Vol 89 (1065) ◽

pp. 20160110 ◽

Cited By ~ 4

Author(s):

Katrina A Morris ◽

Allyson Parry ◽

Pieter M Pretorius

Keyword(s):

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Volumetric Mri ◽

Bevacizumab Treatment ◽

Mri Measurements

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Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type 2

Clinical Neuroradiology ◽

10.1007/s00062-021-01102-5 ◽

2021 ◽

Author(s):

Tim Godel ◽

Philipp Bäumer ◽

Said Farschtschi ◽

Klaus Püschel ◽

Barbara Hofstadler ◽

...

Keyword(s):

Nervous System ◽

Peripheral Nerve ◽

Peripheral Nervous System ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Nerve Lesions ◽

Peripheral Nerve Lesions

Abstract Purpose To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology. Methods In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3–S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14–100 months. In one patient, imaging findings were further correlated to histology. Results Follow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified. Conclusion Peripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.

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Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma

Journal of Clinical Oncology ◽

10.1200/jco.19.01367 ◽

2019 ◽

Vol 37 (35) ◽

pp. 3446-3454 ◽

Cited By ~ 13

Author(s):

Scott R. Plotkin ◽

Dan G. Duda ◽

Alona Muzikansky ◽

Jeffrey Allen ◽

Jaishri Blakeley ◽

...

Keyword(s):

Hearing Loss ◽

Growth Factor ◽

Phase Ii ◽

Standard Dose ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

High Dose ◽

Radiographic Response ◽

Bevacizumab Treatment

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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