The response of spinal cord ependymomas to bevacizumab in patients with neurofibromatosis Type 2

OBJECTIVE People with neurofibromatosis Type 2 (NF2) have a genetic predisposition to nervous system tumors. NF2-associated schwannomas stabilize or decrease in size in over half of the patients while they are receiving bevacizumab. NF2 patients treated with bevacizumab for rapidly growing schwannoma were retrospectively reviewed with regard to ependymoma prevalence and response to treatment. METHODS The records of 95 NF2 patients receiving bevacizumab were retrospectively reviewed with regard to spinal ependymoma prevalence and behavior. The maximum longitudinal extent (MLE) of the ependymoma and associated intratumoral or juxtatumoral cysts were measured on serial images. Neurological changes and patient function were reviewed and correlated with radiological changes. RESULTS Forty-one of 95 patients were found to have ependymomas (median age 26 years; range 11–53 years). Thirty-two patients with a total of 71 ependymomas had scans appropriate for serial assessment with a mean follow-up of 24 months (range 3–57 months). Ependymomas without cystic components showed minimal change in MLE. Twelve patients had ependymomas with cystic components or syringes. In these patients, reductions in MLE were observed, particularly due to decreases in the cystic components of the ependymoma. Clinical improvement was seen in 7 patients, who all had cystic ependymomas. CONCLUSIONS Bevacizumab treatment in NF2 patients with spinal cord ependymomas results in a decrease in the size of intratumoral and juxtatumoral cysts as well as adjacent-cord syringes and a decrease in cord edema. This may provide clinical benefit in some patients, although the changes do not meet the current criteria for radiological tumor response.

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

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0032-1314391 ◽

2012 ◽

Vol 73 (S 02) ◽

Cited By ~ 1

Author(s):

J. Henry ◽

A. Bala ◽

S. Freeman ◽

S. Lloyd ◽

S. Mills ◽

...

Keyword(s):

Peripheral Nerve ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Early Results ◽

Bevacizumab Treatment

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Resection of 2 Intradural Extramedullary Cervical Spine Tumors in a Patient With Neurofibromatosis Type 2: 3-Dimensional Operative Video

Operative Neurosurgery ◽

10.1093/ons/opy149 ◽

2018 ◽

Vol 16 (2) ◽

pp. 274-274

Author(s):

Simone E Dekker ◽

Chad A Glenn ◽

Thomas A Ostergard ◽

Osmond C Wu ◽

Fernando Alonso ◽

...

Keyword(s):

Spinal Cord ◽

Cervical Spine ◽

Treatment Options ◽

Tumor Resection ◽

Neurofibromatosis Type ◽

Cord Compression ◽

Neurofibromatosis Type 2 ◽

3 Dimensional ◽

Intradural Extramedullary

Abstract This 3-dimensional operative video illustrates resection of 2 cervical spine schwannomas in a 19-yr-old female with neurofibromatosis type 2. The patient presented with lower extremity hyperreflexity and hypertonicity. Magnetic resonance imaging (MRI) demonstrated 2 contrast-enhancing intradural extramedullary cervical spine lesions causing spinal cord compression at C4 and C5. The patient underwent a posterior cervical laminoplasty with a midline dural opening for tumor resection. Curvilinear spine cord compression is demonstrated in the operative video. After meticulous dissection, the tumors were resected without complication. The dural closure was performed in watertight fashion followed by laminoplasty using osteoplastic titanium miniplates and screws. Postoperative MRI demonstrated gross total resection with excellent decompression of the spinal cord. The postoperative course was uneventful. The natural history of this disease, treatment options, and potential complications are discussed.

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Bevacizumab for Hearing Preservation in Neurofibromatosis Type 2: Emphasis on Patient-Reported Outcomes and Toxicities

Otolaryngology ◽

10.1177/0194599818809085 ◽

2018 ◽

Vol 160 (3) ◽

pp. 526-532 ◽

Cited By ~ 7

Author(s):

Pavlina Sverak ◽

Meredith E. Adams ◽

Stephen J. Haines ◽

Samuel C. Levine ◽

David Nascene ◽

...

Keyword(s):

Patient Reported Outcomes ◽

Tumor Volume ◽

Neurofibromatosis Type ◽

Hearing Preservation ◽

Neurofibromatosis Type 2 ◽

Hearing Improvement ◽

Radiographic Response ◽

Bevacizumab Treatment ◽

Patient Reported

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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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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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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