SRS for Vestibular Schwannomas in Neurofibromatosis Type 2

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

Download Full-text

Integrated Analysis of Transcriptome and Differential Methylation of Neurofibromatosis Type 2 Vestibular Schwannomas

World Neurosurgery ◽

10.1016/j.wneu.2021.09.094 ◽

2021 ◽

Author(s):

Jianwei Shi ◽

Dafeng Lu ◽

Ruxin Gu ◽

Jing Xie ◽

Li Yu ◽

...

Keyword(s):

Neurofibromatosis Type ◽

Differential Methylation ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Integrated Analysis

Download Full-text

Short-Term Clinico-Radiographic Response to Super-Selective Intra-Arterial Cerebral Infusion of Bevacizumab for the Treatment of Vestibular Schwannomas in Neurofibromatosis Type 2

Interventional Neuroradiology ◽

10.1177/159101991201800201 ◽

2012 ◽

Vol 18 (2) ◽

pp. 127-132 ◽

Cited By ~ 14

Author(s):

H.A. Riina ◽

J-K. Burkhardt ◽

A. Santillan ◽

L. Bassani ◽

A. Patsalides ◽

...

Keyword(s):

Bowel Perforation ◽

Wound Dehiscence ◽

Neurofibromatosis Type ◽

Chemotherapeutic Agents ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Blood Brain Barrier Disruption ◽

Systemic Side Effects ◽

Brain Barrier Disruption

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a prevalence of approximately 1 in 30,000. NF 2 is characterized by bilateral vestibular schwannomas, as well as meningiomas, ependymomas and gliomas. Currently, surgical resection and radiotherapy represent the mainstay of treatment, although new studies suggest a role for certain chemotherapeutic agents. Intravenous administration of Bevacizumab (Avastin, Genetech Pharmaceuticals) has been shown to be active in the treatment of vestibular schwannomas. The IV route of administration, however, carries a risk of known systemic side-effects such as bowel perforation, wound dehiscence and pulmonary embolism. In addition, the percentage of drug that reaches the tumor site may be restricted by the blood tumor barrier. This report describes the super-selective intra-arterial infusion of Bevacizumab following blood brain barrier disruption for the treatment of vestibular schwannomas in three patients with Neurofibromatosis type 2. It represents the first time such a technique has been performed for this disease. Additionally, this method of drug delivery may have important implications in the treatment of patients with vestibular schwannomas associated with Neurofibromatosis type 2.

Download Full-text

Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2

Journal of Neurosurgery ◽

10.3171/jns.2003.99.3.0480 ◽

2003 ◽

Vol 99 (3) ◽

pp. 480-483 ◽

Cited By ~ 62

Author(s):

Goro Otsuka ◽

Kiyoshi Saito ◽

Tetsuya Nagatani ◽

Jun Yoshida

Keyword(s):

Symptom Onset ◽

Survival Rates ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Content Type ◽

Fine Print

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

Download Full-text