scholarly journals Minimal Effect of Bevacizumab Treatment on Residual Vestibular Schwannomas after Partial Resection in Young Neurofibromatosis Type 2 Patients

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1862 ◽  
Author(s):  
Isabel Gugel ◽  
Lan Kluwe ◽  
Julian Zipfel ◽  
Christian Teuber ◽  
Marcos Tatagiba ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Volume ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Neurofibromatosis Type 2 ◽  
Partial Resection ◽  
Vestibular Schwannomas ◽  
Minimal Growth ◽  
Bevacizumab Treatment

Hearing-preserving partial resection of neurofibromatosis type 2 (NF2) associated vestibular schwannomas (VS) is a preferred treatment strategy, particularly for children and adolescents. However, the residual tumors do grow and lead at some point to continued hearing deterioration. An adjuvant bevacizumab treatment may provide an option for slowing down this process. In this retrospective study, we reviewed tumor volume and hearing data of 16 operated VS in nine patients younger than 30 years over a period of 63 to 142 months. All these patients had one or more bevacizumab treatment periods and most of them had a non-treatment period after surgery. Four different patterns of growth were observed for the residual tumors: (1) growth in the non-treatment periods, which slowed down in the treatment periods; (2) growth slowed down in one but not in another on-period; (3) unaffected growth; (4) no or minimal growth regardless of the treatment. Neither radiological regression of tumor volume nor hearing improvement were observed in the treatment periods. Accelerated hearing deterioration was observed in several non-treatment periods, but also in some treatment periods. No straightforward correlation can be drawn between tumor growth and hearing scores. Tumor growth and worsening of hearing between two measurement points were slightly less in the treatment periods; however, the differences were not significant, because variations were large. In conclusion, our comprehensive follow-up on 16 VS in nine NF2 patients did show heterogenous effects of bevacizumab on small residual vestibular schwannomas after surgery both regarding tumor size and hearing preservation. Thus, smaller and slower growing tumor residuals seem to behave differently to bevacizumab than reported for not-operated faster growing VS.

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

2018 ◽  
Vol 160 (3) ◽  
pp. 526-532 ◽  
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.

STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2

Neurosurgery ◽  
2007 ◽  
Vol 60 (3) ◽  
pp. 460-470 ◽  
Author(s):  
David Mathieu ◽  
Douglas Kondziolka ◽  
John C. Flickinger ◽  
Ajay Niranjan ◽  
Richard Williamson ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Factors Affecting

Abstract OBJECTIVE Vestibular schwannomas present significant management challenges in patients with neurofibromatosis Type 2 (NF2). We evaluated the results of gamma knife radiosurgery for the management of these tumors, focusing on tumor response, hearing preservation, and other factors affecting outcomes. METHODS Stereotactic radiosurgery was performed to manage 74 schwannomas in 62 patients. Ipsilateral serviceable hearing was present in 35% of tumors before the procedure. The mean tumor volume was 5.7 cm3. The mean margin and maximum dose used were 14 and 27.5 Gy, respectively. Cox regression analyses were performed to identify factors affecting outcomes. RESULTS The median follow-up period was 53 months, and two patients were lost to follow-up. Actuarial local control rates at were 85, 81, and 81% at 5, 10, and 15 years, respectively. Tumor volume was significant as a predictor of local control. Since 1992, using current radiosurgery techniques (magnetic resonance imaging scan targeting and reduced margin dose to 14 Gy or less), the actuarial serviceable hearing preservation rate is 73% at 1 year, 59% at 2 years, and 48% at 5 years after radiosurgery. Facial neuropathy occurred in 8% of tumors, trigeminal neuropathy occurred in 4%, and vestibular dysfunction occurred in 4%. Radiation dose and tumor volume were predictive of development of new deficits. No radiosurgery-associated secondary tumors or atypical or malignant changes were noted. CONCLUSION Stereotactic radiosurgery is a safe and effective management modality for neurofibromatosis Type 2 vestibular schwannomas. Although results do not seem to be as good as for patients with sporadic unilateral tumors, gamma knife radiosurgery results seem favorable and indicate that radiosurgery should be strongly considered for primary tumor management in selected patients.

Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas

2018 ◽  
Vol 128 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Ivo J. Kruyt ◽  
Jeroen B. Verheul ◽  
Patrick E. J. Hanssens ◽  
Henricus P. M. Kunst
Keyword(s):  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Vestibular Schwannomas ◽  
Tumor Control ◽  
Nerve Function

OBJECTIVENeurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS.METHODSThe authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes.RESULTSActuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS.CONCLUSIONSWith modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm3 seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to medium in size. Larger tumors in patients with the Wishart phenotype appear to respond poorly to radiosurgery, and other treatment modalities should therefore be considered in such cases.

Tumor control and hearing preservation after Gamma Knife radiosurgery for vestibular schwannomas in neurofibromatosis type 2

2010 ◽  
Vol 98 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Manish Singh Sharma ◽  
Rakesh Singh ◽  
Shashank S. Kale ◽  
Deepak Agrawal ◽  
Bhawani Shankar Sharma ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Tumor Control

scholarly journals Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2–Associated Vestibular Schwannomas

2016 ◽  
Vol 34 (14) ◽  
pp. 1669-1675 ◽  
Author(s):  
Jaishri O. Blakeley ◽  
Xiaobu Ye ◽  
Dan G. Duda ◽  
Chris F. Halpin ◽  
Amanda L. Bergner ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Hearing Loss ◽  
Growth Factor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Vascular Endothelial ◽  
Bevacizumab Treatment ◽  
Endothelial Growth Factor

Purpose Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs. Patients and Methods Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers. Results Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell–derived factor 1α (P = .037 and .025, respectively). Conclusion Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies.

Surgical Management of Vestibular Schwannomas in Neurofibromatosis Type 2

2012 ◽  
Vol 73 (S 02) ◽  
Author(s):  
J. Tysome ◽  
R. MacFarlane ◽  
J. Durie-Gair ◽  
N. Donnelly ◽  
R. Mannion ◽  
...  
Keyword(s):  
Surgical Management ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas
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