Treatment Of Vestibular Schwannomas Research Articles

EPHA2 is a Potential Target for the Treatment of NF2-/-Vestibular Schwannoma

Neurofibromatosis type 2 (NF2) is an autosomal dominant cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas secondary to loss of heterozygosity of NF2 in Schwann cells or their precursors. While these tumors are largely benign, they can cause considerable morbidity due to compromised auditory, vestibular, facial, and vertebral nerve function. This may result in deafness, vertigo, facial muscle weakness, chronic neuropathic pain, and even death.There are currently no pharmacotherapies for VS, and surgical resection remains the standard of care, which is associated with significant morbidity. Thus, there is an urgent need to develop pharmaceutical approaches to halt or reverse the progression of tumor growth in NF2 patients who develop VS. Our lab previously identified the receptor tyrosine kinase inhibitors brigatinib and dasatinib as potentially efficacious agents for the treatment of VS and demonstrated that both agents targeted the Ephrin A2 receptor (EPHA2). EPHA2is a transmembrane receptor tyrosine kinase thatis involved in cell contact-mediated motility, adhesion,and migration. Additionally, EPHA2 modulates axon guidance, and synaptogenesis in developing brain. Here we demonstrate that EPHA2expression is increased in NF2-/-Schwanncells and NF2-/-cancers. We identify ponatinib, a receptor tyrosine kinase inhibitor targeting ABL1 that is FDA-approved for CML, as an additional agent that targets EPHA2. We demonstrate that ponatinib treatment impairs the viability of both human and murine NF2-/-Schwanncells in vitro and decreases EPHA2 protein expression. Accordingly, pharmacologic,and siRNA-mediated inhibition of EPHA2 also impaired the growth of human NF2-/-Schwann cells in vitro. Lastly, we demonstrate that both ponatinib and EPHA2 inhibition induce morphological changes in NF2-/-Schwann cells. Our findings suggest that ponatinib or the direct targeting of EPHA2 may be efficacious for the treatment of NF2-associated vestibular schwannoma. Future in vivo efficacystudies are warranted.

Vestibulocochlear Delineation for Vestibular Schwannoma Treated With Radiation Therapy

To develop a specialist-based consensus of cochlear contouring to be used in patients undergoing stereotactic radiosurgery (SRS) treatment for vestibular schwannoma. Representative computed tomography (CT) and magnetic resonance imaging (MRI) were used for cochlear contouring. The semicircles, cochlea, vestibule, and internal acoustic meatus were delineated by 7 radiation oncology department physicians and reviewed by neuroradiologists. A total of 12 cases accrued from a single academic institution were studied for a similarity analysis by the Dice coefficient. The suggested guideline is an easily reproductive tool that allows radiation oncologists to accurately contour the vestibulocochlear system to avoid toxicity due to inadequate dosimetry of organs at risk. This could be a useful tool even for non-vestibular schwannoma radiation therapy. The Dice coefficient suggests reproducible results as long as the following contouring recommendations are observed. The template for vestibulocochlear delineation may be useful for an adequate organs at risk definition. Future studies are required to find specific constraints for each segment of the vestibulocochlear system, and to mitigate interobserver variations.

Cochlear sparing in LINAC-based radiosurgery for vestibular schwannoma: a dosimetric comparison of dynamic conformal arc, IMRT and VMAT treatment plans

BackgroundStereotactic radiosurgery (SRS) is the preferred treatment for vestibular schwannoma (VS) in patients with preserved hearing and tumour diameter < 3 cm. Emerging evidence suggests restricting cochlear dose could preserve hearing. This retrospective replanning study aims to compare dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for superiority of cochlear dose sparing without compromising tumour coverage.MethodsEligibility criteria included sporadic VS, serviceable hearing and availability of CT and MRI for planning. The original gross tumour volume and brainstem OAR volume were retained; the cochlea was newly contoured on the planning CT scan (bone window). Each case was replanned using the three above techniques, prescribing 12 Gy to the 80% isodose line. No dose constraint was applied to the cochlea.ResultsEighteen patients were replanned. Mean tumour volume was 2.25 cc. Tumour coverage and tumour mean dose (DCAT: 14.2, IMRT: 14.6, VMAT: 14.5 Gy) were comparable. Paddick and RTOG conformity indices were better for DCAT (0.66 and 1.6) and VMAT (0.69 and 1.5) compared to IMRT (0.56 and 1.9). DCAT had superior gradient index (3.0) compared to VMAT (3.4) and IMRT (3.4). VMAT delivered the lowest mean brainstem maximum dose (8.3 Gy) and decreased the mean cochlear dose (3.4 Gy) by 2.3 and 2.1 Gy, and the mean cochlear maximum dose (3.6 Gy) by 2.4 and 2.5 Gy relative to DCAT and IMRT, respectively.ConclusionLINAC-based SRS treatment using VMAT can achieve better cochlear dose sparing than DCAT or IMRT while maintaining tumour coverage.

A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome.

Both stereotactic radiosurgery (SRS) and microsurgical resection (SURGERY) are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. This present study aimed to compare the nuances in the treatment of VS by SURGERY and SRS in 2 highly specialized neurosurgical centers. This is a retrospective bicentric cohort study. Data from patients treated between 2005 and 2011 were collected retrospectively. Recurrence-free survival (RFS) was assessed radiographically by contrast-enhanced magnetic resonance imaging. The study population included N = 901 patients with a mean follow-up of 7 years. Overall, the incidence of recurrence was 7% after SURGERY, and 11% after SRS with superior tumor control in SURGERY in the Kaplan-Meier-analysis (P = 0.031). In small tumors (Koos I and II), tumor control was equivalent in both treatment arms. In large VS (Koos III and IV), however, RFS was superior in SURGERY. The extent of resection correlated with RFS (P < .001). Facial and hearing deterioration was similar in both treatment arms in small VS, but more pronounced in SURGERY of large VS. Tinnitus, vertigo, imbalance, and trigeminal symptoms were more often improved by SURGERY than SRS. SRS can achieve similar tumor control compared to SURGERY in smaller VS (Koos I and II)-with similar postinterventional morbidities. In large VS (Koos III and IV), long-term tumor control of SRS is inferior to SURGERY. Based on these results, we suggest that if combination therapy is chosen, the residual tumor should not exceed the size of Koos II.

Vestibular Schwannoma

Abstract Vestibular schwannoma is a tumor of vestibulocochlear nerve and is a rare intracranial tumor. The presenting complaints of a 57-year-old man who had been referred to the ENT outpatient department from a primary care provider for evaluation and management of left side vestibular schwannoma discovered on computerized tomography scan brain were insidious onset of hearing loss for the last 4 years, headache for the last 1 year which has worsened for the last 2 months and associated with vomiting episodes, along with imbalance while walking. The patient’s symptoms, tumor size, growth rate, age, and life expectancy determine the treatment of vestibular schwannoma. The above patient was advised surgery along with magnetic resonance imaging brain and preoperative investigations which the patient has agreed to do at a higher referral center of his choice.

SRS for Vestibular Schwannomas - Current Status.

Stereotactic radiosurgery (SRS) is an established modality of treatment for vestibular schwannomas (VS). We aim to summarize the evidence-based use of SRS in VSs and address the specific considerations pertaining to the same, along with our own clinical experiences. A thorough review of the literature was done to gather evidence regarding the safety and efficacy of SRS in VSs. Additionally, we have reviewed the senior author's experience in treating VSs (N = 294) between 2009 and 2021 and our experiences with microsurgery in post-SRS patients. Available scientific evidence upholds the role of SRS in VSs, in small-to-medium-sized tumors (5-year local tumor control >95%). The risk of adverse radiation effects remains minimal, while the hearing preservation rates are variable. Our center's post-GammaKnife VS follow-up cohort (sporadic - 157, neurofibromatosis-2 - 14) showed excellent tumor control rates at the last follow-up of 95.5% (sporadic) and 93.8% (neurofibromatosis-2), with a median margin dose of 13 Gy and mean follow-up periods of 3.6 (sporadic) and 5.2 (neurofibromatosis-2) years. Microsurgery in post-SRS VSs poses a formidable challenge due to the resulting thickened arachnoid and adhesions to critical neurovascular structures. Near-total excision is the key to better functional outcomes in such cases. SRS is here to stay as a trusted alternative in the management of VSs. Further studies are required to propose means of accurate prediction of hearing preservation rates and also to compare the relative efficacies of various SRS modalities.

Single-fraction stereotactic radiosurgery versus microsurgical resection for the treatment of vestibular schwannoma: a systematic review and meta-analysis

BackgroundVestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma.MethodsWe searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm).ResultsWe identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02–0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life.ConclusionsOur systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful.Systematic review registrationThe full (German language) protocol and report (Commission No. N20-03) are available on the institute’s website: www.iqwig.de/en/projects/n20-03.html

Decision Making for Active Surveillance in Vestibular Schwannoma.

To describe the experiences of patients who elected for the active surveillance treatment option for their vestibular schwannoma (VS). Twenty-two patients participated in semistructured patient interviews. Interviews were conducted between March and April 2021 via telephone with audio recordings and notes taken during each interview. Adults diagnosed with a VS and at any point after their diagnosis underwent a period of active surveillance were recruited based on the diagnosis made by MRI. Patients were excluded if they chose to undergo treatment immediately, had a diagnosis of neurofibromatosis type 2, or if they had a confirmed alternative diagnosis. This intervention was a qualitative interview to assess patient experiences with their VS treatment decision. Identifying abstract categories that represent many of the stories told by the participants that produces a theory grounded in the data with explanatory power. Factors that influenced patients' treatment decisions were perceived physician bias, selfeducation, and personal accounts of VS patients through support groups, and side effects/complications of the various treatment options. Patients who opted for active surveillance as a treatment option reported high satisfaction with their decision and greater confidence in future treatments that would be necessary based on tumor growth. Future work should be done to increase shared decision making between the physician and patient to arrive at a treatment plan that aligns with their goals of care as well as potentially reducing overtreatment of VS.

MRI Changes in Failed Radiosurgery for Vestibular Schwannomas

Introduction: Radiosurgery is now a recognized treatment of vestibular schwannoma (VS); however, radiosurgical irradiation sometimes fails to stop tumor growth in the long term. Some changes in MR imaging after radiosurgery that are supposed to be related to permanent tumor control may be observed in patients with failed treatment. The objective of the present study was to evaluate the MRI changes observed early after radiosurgery in a cohort of patients with failed radiosurgery for VS. Methods: From a large series of VS treated radiosurgically for 15 years, we reviewed the follow-up MRI data in a subgroup of VS that presented obvious treatment failure. T1-weighted MR imaging with standard timing of gadolinium injection was applied for image acquisition during the radiosurgical procedure and all follow-up MR imaging. Evolution of tumor volume and contrast enhancement were assessed on 3D-co-registered MRI. Results: Twenty-nine of 728 patients (4%) were retreated for the same VS after >2 years (median 3.14 years, range 2.04–9.47) following initial radiosurgical treatment. The median tumor volume was 0.94 cc at first radiosurgical treatment and 2.19 cc at retreatment. Fourteen patients (48.3%) had continuous increase in tumor volume. For 10 patients (34.5%), the tumor volume reduced significantly after irradiation before it increased again. Four patients (13.8%) showed a transient increase in tumor volume after irradiation, followed by significant volume reduction, then a very significant tumor regrowth. A significant loss of contrast enhancement at the center of the tumor was observed for 25 patients (86.2%); full recovery of contrast enhancement of the tumor was observed for 23 patients. Discussion/Conclusion: Tumor volume reduction and central loss of contrast enhancement of the tumor are MRI changes frequently observed during follow-up of VS treated radiosurgically even in patients with failed long-term tumor control and may therefore not be considered as signs of successful response of the tumor to the radiosurgical treatment.

Single-Fraction vs. Fractionated Stereotactic Radiosurgery for Vestibular Schwannomas with Frameless Radiosurgery: A Single Institution Prospective Observational Study

<h3>Purpose/Objective(s)</h3> The number of patients with small- to medium-sized vestibular schwannoma (VS), defined as under 22 mm in greatest dimension, presenting with serviceable hearing has steadily increased over the last 50 years. Thus, treatment of VS often must balance a goal of tumor control with hearing preservation and other potential side effects. Improved hearing rates have been demonstrated with the use of a lower prescription dose. The effect of fractionation in preserving hearing loss is less clear. We sought to evaluate local control and hearing preservation rates in patients treated with single-fraction versus 5-fraction frameless GKRS. <h3>Materials/Methods</h3> Prospectively enrolled patients with a radiographic diagnosis of unilateral vestibular schwannoma who underwent single-fraction or 5-fraction definitive frameless GKRS between 2017 and 2020 were retrospectively reviewed in our institutional review board (IRB) approved database. We used chi-squared tests and t-tests to compare demographic and clinical characteristics by treatment modality. We then used Kaplan-Meier methods to compare the two treatment groups' local control and hearing preservation, and evaluated the statistical significance of the differences by log rank test. <h3>Results</h3> Seventy consecutive patients were treated with single-fraction or fractionated GKRS for VS from 2017 to 2020. Forty-eight patients met inclusion criteria and were included in this analysis. Twenty-three patients underwent single-fraction treatment, and 25 patients underwent fractionated treatment in 5 fractions. Median follow-up time was 2 years for both groups. Patients who were treated with multi-fraction GKRS on average, had a larger maximal tumor diameter than those treated with single-fraction GKRS. At 2 years, radiographic local control of VS treated with single-fraction was 93% compared to 92% for multi-fraction frameless GKRS (p=0.64). No patients required salvage treatment in either group. Hearing preservation was evaluated in patients with available audiograms (13/23 single-fraction and 20/25 multi-fraction). At 2 years, hearing preservation was 46% for patients treated with single-fraction GKRS compared to 78% for patients treated with multi-fraction GKRS, not including patients censored due to lack of available audiogram (p=.06). <h3>Conclusion</h3> Single-fraction and fractionated frameless GKRS provide similar clinical and radiographic local control, while maintaining similar hearing preservation rates, in the treatment of VS.

Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.

To determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS). Prospective study. Single institution, academic tertiary care lateral skull base surgery program. Patients diagnosed with VS. A comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool. Pre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared. A pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p < 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction. Implementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future.

Novel Multiportal Approach to the Internal Auditory Canal for Hearing-Preserving Surgery: Feasibility Assessment in Dissections

State-of-the-art, minimally invasive endoscopic transcanal surgery of the internal auditory canal (IAC) sacrifices the cochlea with complete hearing loss. With a combination of the transcanal infracochlear and transmastoid retrolabyrinthine approaches, we aim to preserve hearing and enable minimally invasive surgical treatment of vestibular schwannoma. In this study, we investigate the anatomical indications and the feasibility of both approaches in dissections, in human whole head specimens. We operated whole head anatomical specimens with a four-handed technique, using the retrolabyrinthine approach as the main surgical corridor and the infracochlear approach for endoscopic visualization. We tested 4 different powered surgical systems. We collected intraoperative data on the size of the access windows, the surgical freedom, and the exposed area of the IAC. Finally, we evaluated the outcome in postoperative computed tomography scans. Six out of 14 sides were anatomically suitable and qualified for the surgery based on preoperative computed tomography. In all attempted sides, the IAC could be reached and opened, leaving the ossicular chain and the labyrinth intact. 51%-75% of the length and 22%-40% of the circumference of the IAC could be exposed. All tested instruments were beneficial at different stages of the surgery. The four-handed technique enabled good maneuverability of the instruments. The combined multiportal approach to the IAC is feasible with a good surgical exposure and full anatomical preservation of hearing. State-of-the-art surgical instruments in specimens with suitable anatomy are sufficient to perform this approach.

Surgical treatment for vestibular schwannoma in patients aged ≥65-years: A retrospective multi-centric study

• The present study aimed to evaluate the role of vestibular schwannoma surgery in ≥ 65-year-old patients • Age alone was not statistically correlated to worse either surgical or functional outcomes • Postoperatively, an immediate significant worsening of the post-operative KPS was observed • However, at a 6-month follow-up, a significant improvement in KPS was found, even over the preoperative one • Improvements between the immediate and the 6-month follow-up KPS were significant for patients aged between 65-70 and 70-75

Role of microRNAs as novel diagnostic biomarkers and potential therapeutic targets for hearing disorders (Review)

The ear is a complex structure consisting of the outer, middle and inner ear. For the proper function of the auditory system, the development of all these parts needs to be highly organized. Any alterations in this chain of events can lead to hearing loss or other impairments, such as dizziness, tinnitus and loss of balance. Of note, several external and internal elements, including noise exposure, ototoxic drugs, aging, as well as environmental or genetic factors, have been widely associated with hearing loss. Over the years, a growing body of evidence has indicated that microRNAs (miRNAs/miRs) play a critical role in ear development and auditory function, suggesting that an altered pattern of miRNA expression may be involved in the progression of these pathological conditions. On these bases, the present review article aimed to summarize the role of miRNAs in inner ear development and hearing disorders. Although further studies are warranted to provide more in‑depth knowledge of the implicated mechanisms of action, according to the current data, miRNAs may be used as novel diagnostic biomarkers for the early detection of hearing loss. In addition, miRNAs and related signaling pathways may represent novel potential therapeutic targets for the treatment of hearing loss, ear inflammation and vestibular schwannoma.

The longitudinal volumetric response of vestibular schwannomas after Gamma Knife radiosurgery.

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I-IV VS after radiosurgery. A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification. Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ± 2.82 cm3 (range 0.12-18.77 cm3) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18-54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS. Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

Phenotypical Variability of the Internal Acoustic Canal in the Middle Cranial Fossa Surgery.

Introduction The wide range of anatomical variability of the structures of the middle cranial fossa (MCF) and the lack of reliable surgical landmarks contribute to a high level of complications in the surgical treatment of vestibular schwannomas. We hypothesized that the cranial phenotype influences the shape of the MCF, the orientation of the pyramid of the temporal bone, and the relative topography of the internal acoustic canal (IAC). Methods The skull base structures were studied on 54 embalmed cadavers and 60 magnetic resonance images of the head and neck by photo modeling, dissection, and three-dimensional analysis techniques. By the value of the cranial index, all specimens were subdivided into dolichocephalic, mesocephalic, and brachycephalic groups for comparison of variables. Results The length of the superior border of the temporal pyramid (SB), the apex to squama distance, and the width of the MCF all peaked in the brachycephalic group. The value of the angle between the SB and the axis of the acoustic canal varied from 33 to 58 degrees; it peaked in the dolichocephalic group and showed its smaller value in the brachycephalic one. The pyramid to squama angle had reversed distribution and dominated in the brachycephalic group. Conclusion The cranial phenotype influences the shape of the MCF, temporal pyramid, and IAC. Presented in this article data help specialists operating on the vestibular schwannoma to localize the IAC based on the individual shape of a skull.

Repeat single-fraction stereotactic radiosurgery for recurrent vestibular schwannoma.

BackgroundData are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up.Materials and methodsWe retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy.ResultsFollow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit.ConclusionThere was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.

Manajemen Anestesi Reseksi Tumor Cerebello-pontine Angle Vestibular Schwannoma dengan Posisi Lateral

Cerebellopontine angle (CPA) tumors are the most common neoplasms in the posterior fossa, accounting for 5-10% of intracranial tumors. Most CPA tumors are benign, with over 85% being vestibular schwannoma (acoustic neuromas). The preferred treatment for symptomatic vestibular schwannoma has been surgical excision. Craniotomy for vestibular schwannoma resections in lateral position gave better surgical field exposure, but also posed increased risk of ventilation-perfusion mismatch and atelectasis of the dependent lung in lengthy surgery. A 25 years old woman, with loss of hearing function, disturbed sense of balance, left hemiplegia, difficulties to swallow, on magnetic resonance imaging (MRI) examination had solid lesion in the cerebello-pontine angle size 5,6 cm x 5 cm x 4.5 cm which is diagnosed as Cerebello-pontine angle vestibular schwannoma sinistra. Patient underwent surgical resection in right lateral position under general anesthesia and the surgical resection performed in 6 hour 40 minutes. The goals of anesthetic management in vestibular schwannoma tumor resection are to facilitate ideal surgical condition and provide brain protection by maintaining cerebral perfusion pressure, avoid hemodynamic instability, enable intraoperative neuro-monitoring and ensure the early detection and prompt management of potential complications.

Simultaneous Surgical Treatment of Vestibular Schwannoma and Hemifacial Spasm via Minimally Invasive Retrosigmoid Approach

The combination of vestibular schwannoma (VS) and hemifacial spasm (HFS) caused by a vascular loop is not frequently encountered. Surgical intervention using the retrosigmoid approach may enable the two diseases to be treated simultaneously. A 68-year-old male presented with progressive right HFS. MRI revealed a concurrent vascular loop and 3.2-mm intracanalicular VS. The retrosigmoid approach, together with microvascular decompression, was used to remove VS. Intraoperatively, compression by the vascular loop alone induced HFS although it was not related to VS. This finding is in contrast to the literature reports in which VS has been implicated in HFS. In our patient, when VS was completely removed, HFS immediately disappeared postoperatively.

A Critical Overview of Targeted Therapies for Vestibular Schwannoma.

Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.