Unilateral Vestibular Schwannoma Research Articles

Recurrences and progression following microsurgery of vestibular schwannoma.

The treatment approach of vestibular schwannoma (VS) has seen a change in recent years, with a trend away from radical surgery towards preservation of cranial nerve function. A recent study reported recurrences as long as 20 years after complete removal of VS. To report the risk of recurrence and progression in our patient population the authors retrospectively reviewed outcomes of patients. Cases with unilateral VS who had undergone primary microsurgery via retrosigmoidal approach between 1995 and 2021 were investigated. Complete tumor removal was defined as gross total resection (GTR), a capsular remnant was categorized as near total resection (NTR) and residual tumor was designated as subtotal resection (STR). The primary endpoint was radiological recurrence-free survival. 386 patients fulfilled the inclusion criteria of the study and were evaluated. GTR was achieved in 284 patients (73.6%), NTR was achieved in 63 patients (10.1%) and STR was present in 39 patients (16.3%). A total of 28 patients experienced recurrences with significant differences in the three subgroups. The strongest predictor of recurrence was the extent of resection, with patients who underwent STR having an almost 10-fold higher risk of recurrence and patients who had undergone NTR having an almost 3-fold higher risk than those treated with GTR. More than 20% of recurrences (6/28) occured after more than 5 years. The degree of resection is an important guide to the interval of follow-up, but long-term follow-up should be considered also in the case of GTR. The majority of recurrences occurs after 3-5 years. Nevertheless, a follow-up of at least 10 years should be carried out.

Vestibular dysfunction in neurofibromatosis type 2-related schwannomatosis.

Neurofibromatosis type 2-related schwannomatosis is a genetic disorder characterized by neurologic tumours, most typically vestibular schwannomas that originate on the vestibulo-cochlear nerve(s). Although vestibular symptoms can be disabling, vestibular function has never been carefully analysed in neurofibromatosis type 2-related schwannomatosis. Furthermore, chemotherapy (e.g. bevacizumab) can reduce tumour volume and improve hearing in neurofibromatosis type 2-related schwannomatosis, but nothing is known about its vestibular effects. In this report, we studied the three primary vestibular-mediated behaviours (eye movements, motion perception and balance), clinical vestibular disability (dizziness and ataxia), and imaging and hearing in eight untreated patients with neurofibromatosis type 2-related schwannomatosis and compared their results with normal subjects and patients with sporadic, unilateral vestibular schwannoma tumours. We also examined how bevacizumab affected two patients with neurofibromatosis type 2-related schwannomatosis. Vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis degraded vestibular precision (inverse of variability, reflecting a reduced central signal-to-noise ratio) but not vestibular accuracy (amplitude relative to ideal amplitude, reflecting the central signal magnitude) and caused clinical disability. Bevacizumab improved vestibular precision and clinical disability in both patients with neurofibromatosis type 2-related schwannomatosis but did not affect vestibular accuracy. These results demonstrate that vestibular schwannoma tumours in our neurofibromatosis type 2-related schwannomatosis population degrade the central vestibular signal-to-noise ratio, while bevacizumab improves the signal-to-noise ratio, changes that can be explained mechanistically by the addition (schwannoma) and suppression (bevacizumab) of afferent neural noise.

Pseudoprogression of Vestibular Schwannoma after Stereotactic Radiosurgery with Cyberknife®: Proposal for New Response Criteria

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20-82) years, the median initial tumor volume was 1.5 (range: 0.1-8.6) cm3. The median radiological and clinical follow-up time was 66 (range: 24-103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation.

The characteristics of brain structural remodeling in patients with unilateral vestibular schwannoma.

Brain structural remodeling alters related brain function. However, few studies have assessed morphological alterations of unilateral vestibular schwannoma (VS) patients. Therefore, this study examined the characteristics of brain structural remodeling in unilateral VS patients. We recruited 39 patients with unilateral VS (19 left, 20 right) and 24 matched normal controls (NCs). We obtained brain structural imaging data using 3T T1-weighted anatomical and diffusion tensor imaging scans. Then, we evaluated both gray and white matter (WM) changes using FreeSurfer software and tract-based spatial statistics, respectively. Furthermore, we constructed a structural covariance network to assess brain structural network properties and the connectivity strength between brain regions. Compared with NCs, VS patients showed cortical thickening in non-auditory areas (e.g., the left precuneus), especially left VS patients, along with reduced cortical thickness in the right superior temporal gyrus (auditory areas). VS patients also showed increased fractional anisotropy in extensive non-auditory-related WM (e.g., the superior longitudinal fasciculus), especially right VS patients. Both left and right VS patients showed increased small-worldness (more efficient information transfer). Left VS patients had a single reduced-connectivity subnetwork in contralateral temporal regions (right-side auditory areas), but increased connectivity between some non-auditory regions (e.g., left precuneus and left temporal pole). VS patients exhibited greater morphological alterations in non-auditory than auditory areas, with structural reductions seen in related auditory areas and a compensatory increase in non-auditory areas. Left and right VS patients show differential patterns of brain structural remodeling. These findings provide a new perspective on the treatment and postoperative rehabilitation of VS.

Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma.

Tinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear. Both preoperative (VS pre ) and postoperative (VS post ) functional MR images were collected from 32 patients with unilateral VS and matched healthy controls (HCs). Connectome gradients were generated for the identification of altered regions and perturbed gradient distances. Tinnitus measurements were conducted for predictive analysis with neuroimaging-genetic integration analysis. There were 56.25% of preoperative patients and 65.63% of postoperative patients suffering from ipsilateral tinnitus, respectively. No relevant factors were identified including basic demographics info, hearing performances, tumor features, and surgical approaches. Functional gradient analysis confirmed atypical functional features of visual areas in VS pre were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VS post vs. HC : P = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus (P FDR = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score (r = -0.30, P = 0.013), THI level (r = -0.31, P = 0.010), and visual analog scale (VAS) rating (r = -0.31, P = 0.0093), which could be used to predict VAS rating in the linear model. Neuropathophysiological features linked to the tinnitus gradient framework were linked to Ribosome dysfunction and oxidative phosphorylation. Altered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.

The Course of Hearing Loss in Patients With a Progressive Vestibular Schwannoma.

This study evaluates the natural course of hearing loss (HL) prior to treatment in patients with progressive tumors and an indication for active intervention. Evaluating this patient group specifically can put hearing outcomes after vestibular schwannoma therapy into an adequate context. Retrospective cohort study. Tertiary referral center. Inclusion criteria comprised unilateral vestibular schwannomas prior to active treatment, with ≥2 mm extracanalicular (EC) tumor growth and ≥2 audiograms. We performed a comprehensive assessment of hearing using multiple outcome parameters including (the annual decrease in) pure-tone averages (PTAs; an average of 0.5, 1, 2, and 3 kHz). Predictors for HL were evaluated (patient age, tumor size/progression, follow-up duration, baseline hearing). At presentation, 86% of patients suffered from sensorineural HL on the affected side (≥20 dB PTA) with a median of 39 dB (interquartile rate [IQR]: 27-51 dB). The median follow-up duration was 21 months (IQR: 13-34 months), after which 58% (187/322) of patients experienced progressive HL (≥10 dB), with a median increase of 6.4 dB/year. At the last follow-up, the median PTA was 56 dB (IQR: 37-73). Median speech discrimination scores deteriorated from 90% (IQR: 70%-100%) to 65% (IQR: 35%-100%). Tumor progression (maximal EC diameter) was significantly correlated to the progression of sensorineural HL, corrected for follow-up (F(2,228) = 10.4, p < .001, R2 = 8%). The majority of patients (58%) with radiologically confirmed progressive vestibular schwannomas experience progressive sensorineural HL during observation. Tumor progression rate, ECtumor extension, and longer follow-up are factors associated with more sensorineural HL.

Twelve-Month Outcomes of Simultaneous Translabyrinthine Resection and Cochlear Implantation.

Audiometric outcomes at 12 months following simultaneous translabyrinthine (TL) resection of vestibular schwannoma (VS) and cochlear implantation (CI). Prospective cohort study. Tertiary referral center. Adult patients undergoing TL resection of sporadic, unilateral VS ≤ 2 cm were prospectively enrolled. Preoperative testing included binaural AZBio in noise and quiet and unilateral Consonant-Nucleus-Consonant (CNC). Tinnitus Handicap Index (THI) and Speech, Spatial, and Qualities of Hearing (SSQ) questionnaires were also completed. Patients underwent TL resection with simultaneous CI. The preoperative test battery was repeated at 1, 3, 6, and 12 months after activation. Statistical analysis was performed to characterize short-term outcomes (preoperative to 3 months), longer-term outcomes (3-12 months), and overall changes during the preoperative to 12-month period. AZBio, CNC, and THI improved at 3 months with no significant changes thereafter and showed durable improvement at 12 months compared to preoperative testing. While SSQ did not improve at 12 months, a subset of patients showed either recovery or improvement of SSQ-spatial subscores. Patients with cerebellopontine angle tumors had poorer performance, although the impact of tumor size and location could not be deduced based on the small sample size. Patients undergoing simultaneous CI and TL resection of VS had durable improvements in speech perception and tinnitus severity 12 months following surgery. Subjective improvements in localization were not observed. Additional studies are needed to determine which VS patients are optimal candidates for CI.

Functional Outcome After Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation With Intraoperative Cochlear Nerve Monitoring.

Electrically evoked auditory brainstem response audiometry has emerged as a suitable option to intraoperatively assess cochlear nerve function during vestibular schwannoma resection. This study aimed to analyze the functional outcome and implant usage of patients with preserved auditory nerve responses after simultaneous translabyrinthine schwannoma resection and cochlear implantation. Prospective study. Tertiary referral center. Patients with unilateral sporadic vestibular schwannoma underwent translabyrinthine tumor resection. Intraoperatively, electrically evoked auditory brainstem response audiometry was performed before and after tumor removal. Cochlear implantation was carried out if positive responses were detected after tumor removal indicating cochlear nerve function. Postoperatively, patients were biannually followed-up to assess aided sound field audiometry and word recognition as well as implant usage. Overall, 26 patients with vestibular schwannoma underwent translabyrinthine schwannoma resection. Out of these patients, 15 had positive cochlear nerve responses after tumor removal and concurrently received a cochlear implant. In 13 patients with histologically confirmed vestibular schwannoma, hearing improved by 23.7 ± 33.2 decibels and word recognition by 25.0 ± 42.4% over a mean follow-up period of 18 months. Overall, 12 included patients were regular cochlear implant users. Patients with vestibular schwannoma can benefit substantially from cochlear implantation. Intraoperative assessment of cochlear nerve function using electrically evoked auditory brainstem response audiometry can help to better identify individuals eligible for simultaneous vestibular schwannoma resection and cochlear implantation.

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

Vestibular Complaints Impact on the Long-Term Quality of Life of Vestibular Schwannoma Patients.

To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma. In this cross-sectional study, patients with a unilateral vestibular schwannoma diagnosed between 2004 and 2013 completed a disease-specific QoL questionnaire (Penn Acoustic Neuroma Quality of Life [PANQOL]) and the Dizziness Handicap Inventory (DHI) in 2020. Linear regression was performed to assess the correlation between QoL and the DHI total score, and the scores of the DHI functional, emotional, and physical subdomains. Potential confounders such as age, sex, tumor size at baseline, and treatment modality (active surveillance, surgery, or radiotherapy) were included in the model. In total, 287 of 479 patients (59%) experienced dizziness with a median follow-up of 10 years. The DHI total score was significantly associated with the PANQOL total score. On average, we found a reduction of 0.7 points on the PANQOL for each additional point on the DHI. The DHI emotional subdomain was the most prominent determinant of poorer QoL. Each point on the DHI emotional subscale was associated with a reduction of 1.3 on the PANQOL score. Treatment modality did not have a clinically relevant effect on dizziness-related QoL. Even mild dizziness can have a significant and clinically relevant effect on the QoL of patients with unilateral vestibular schwannoma in the long term. This holds true for all treatment modalities. Addressing the vestibular problems may improve QoL in vestibular schwannoma patients, and DHI subscale analysis may help tailor the optimal vestibular intervention.

ODP561 Unilateral Vestibular Schwannoma as the Presentation and Aggravation to be Severe Primary Hyperparathyroidism

Abstract Background A rare benign and slow-growing tumor as vestibular schwannoma (acoustic neuroma) usually presents with asymptomatic/unilateral hearing loss or tinnitus and loss of balance between the ages of 49 to 60 years. 90% of vestibular schwannoma are unilateral and not specifically grown in patients with neurofibromatosis type2 (NF2) (1). The association of schwannoma and parathyroid adenoma has been published not much but consistently until now. However, those were not mention to the relationship between pre- and post-treatment of schwannoma with parathyroid hormone level. Clinical case: A 65-year-old woman, previously healthy, presented with progressive fatigue and loss of balance for 1 month. She developed hearing loss, dysarthria and facial palsy within 1 week. At her first visited, she looked drowsiness and had slow verbal and motor response with right facial palsy, lower motor neuron type. She lost only her right facial sensation by pinprick and hyperreflexia without significant other neurological deficits and abnormal skin lesions. She denied family history of NF2. Severe hypercalcemia (17.66 mg/dL) with markedly elevated parathyroid hormone (PTH 1,115.1 pg/mL; 15-68.3) levels and mild elevation of serum creatine (Cr 1.32 mg/dL) was revealed. MRI brain showed an extra-axial enhancing mass at right CPA-IAC region size 3.7×4.2×2.9 cm possible vestibular schwannoma, this mass causing pressure effect to right sided of pons, medulla, cerebellar hemisphere and fourth ventricle. After treatment with saline hydration, her serum creatinine was recovered to normal range with slightly high normal serum calcium (11.85 mg/dL) but not being well. She came back to hospital again with fatigue and polyuria for 3 days. Her serum calcium rose up to 21.3 mg/dL with very high PTH level; 1,643 pg/mL and elevation of serum creatine (Cr 1.71 mg/dL). Again, she was treated with saline hydration for 3 days before receiving zoledronate 4 mg intravenously. After that her serum calcium and creatinine returned to normal level (Ca 10.32 mg/dL, Cr 1. 08 mg/dL) with being better. She was undergone surgery for removal right vestibular tumor and proved to be schwannoma in pathology. During further investigation of hyperparathyroidism, she had normocalcemia and her PTH level dropped to about 400 pg/mL. Conclusion Our patient showed the contribution of vestibular schwannoma to rise up the level of PTH as same level as parathyroid carcinoma. There could be some relationships of mechanism between there two diseases that should be explored further. Reference: 1. Carlson ML, Link MJ. Vestibular Schwannomas. Review article. N Engl J Med 384;14,Apr 8, 2021. Presentation: No date and time listed

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.

Significance of Preoperative Nerve Reconstruction Using Diffusion Tensor Imaging Tractography for Facial Nerve Protection in Vestibular Schwannoma.

The facial nerve trace on the ipsilateral side of the vestibular schwannoma was reconstructed by diffusion tensor imaging tractography to identify the adjacent relationship between the facial nerve and the tumor, and to improve the level of intraoperative facial nerve protection. The clinical data of 30 cases of unilateral vestibular schwannoma who underwent tumor resection via retrosigmoid approach were collected between January 2019 and December 2020. All cases underwent magnetic resonance imaging examination before operation. Diffusion tensor imaging and anatomical images were used to reconstruct the facial nerve track of the affected side, so as to predict the course of the nerve and its adjacent relationship with the tumor, to compare the actual trace of the facial nerve during operation, verify the degree of coincidence, and evaluate the nerve function (House-Brackmann grade) after surgery. The facial nerve of 27 out of 30 cases could be displayed by diffusion tensor imaging tractography, and the tracking rate was 90% (27/30). The intraoperative locations of facial nerve shown in 25 cases were consistent with the preoperative reconstruction results. The coincidence rate was 92.6% (25/27). The facial nerves were located on the anterior middle part of the tumor in 14 cases, anterior upper part in eight cases, anterior lower part in seven cases, and superior polar in one case. Intraoperative facial nerve anatomy was preserved in 30 cases. Among the 30 patients, total resection was performed in 28 cases and subtotal resection in two cases. The facial nerve function was evaluated 2 weeks after operation, and the results showed grade I in 12 cases, grade II in 16 cases and grade III in two cases. Preoperative diffusion tensor imaging tractography can clearly show the trajectory and adjacent position of the facial nerve on the side of vestibular schwannoma, which is beneficial to accurately identify and effectively protect the facial nerve during the operation, and is worthy of clinical application and promotion.

Evidence-based surveillance protocol for vestibular schwannomas: a long-term analysis of tumor growth using conditional probability.

The growth characteristics of vestibular schwannomas (VSs) under surveillance can be studied using a Bayesian method of growth risk stratification by time after surveillance onset, allowing dynamic evaluations of growth risks. There is no consensus on the optimum surveillance strategy in terms of frequency and duration, particularly for long-term growth risks. In this study, the long-term conditional probability of new VS growth was reported for patients after 5 years of demonstrated nongrowth. This allowed modeling of long-term VS growth risks, the creation of an evidence-based surveillance protocol, and the proposal of a cost-benefit analysis decision aid. The authors performed an international multicenter retrospective analysis of prospectively collected databases from five tertiary care referral skull base units. Patients diagnosed with sporadic unilateral VS between 1990 and 2010 who had a minimum of 10 years of surveillance MRI showing VS nongrowth in the first 5 years of follow-up were included in the analysis. Conditional probabilities of growth were calculated according to Bayes' theorem, and nonlinear regression analyses allowed modeling of growth. A cost-benefit analysis was also performed. A total of 354 patients were included in the study. Across the surveillance period from 6 to 10 years postdiagnosis, a total of 12 tumors were seen to grow (3.4%). There was no significant difference in long-term growth risk for intracanalicular versus extracanalicular VSs (p = 0.41). At 6 years, the residual conditional probability of growth from this point onward was seen to be 2.28% (95% CI 0.70%-5.44%); at 7 years, 1.35% (95% CI 0.25%-4.10%); at 8 years, 0.80% (95% CI 0.07%-3.25%); at 9 years, 0.47% (95% CI 0.01%-2.71%); and at 10 years, 0.28% (95% CI 0.00%-2.37%). Modeling determined that the remaining lifetime risk of growth would be less than 1% at 7 years 7 months, less than 0.5% at 8 years 11 months, and less than 0.25% at 10 years 4 months. This multicenter study evaluates the conditional probability of VS growth in patients with long-term VS surveillance (6-10 years). On the basis of these growth risks, the authors posited a surveillance protocol with imaging at 6 months (t = 0.5), annually for 3 years (t = 1.5, 2.5, 3.5), twice at 2-year intervals (t = 5.5, 7.5), and a final scan after 3 years (t = 10.5). This can be used to better inform patients of their risk of growth at particular points along their surveillance timeline, balancing the risk of missing late growth with the costs of repeated imaging. A cost-benefit analysis decision aid was also proposed to allow units to make their own decisions regarding the cessation of surveillance.

Is There an Inherited Contribution to Risk for Sporadic Unilateral Vestibular Schwannoma? Evidence of Familial Clustering.

Unlike the autosomal dominant inheritance of neurofibromatosis 2, there are no known inherited risk factors for sporadic, unilateral vestibular schwannoma (VS), which comprise most VS cases. The authors tested a hypothesis positing a genetic contribution to predisposition to these lesions by analyzing familial clustering of cases. Familial clustering of individuals with unilateral VS was analyzed in two independent genealogical resources with linked diagnosis data: the Veterans Health Administration Genealogy Resource and the Utah Population Database. Tests for excess relatedness, estimation of relative risks (RRs) in close and distant relatives, and identification of pedigrees with a significant excess of unilateral VS among descendants were performed. The average pairwise relatedness of the Veterans Health Administration Genealogy Resource VS cases significantly exceeded the expected relatedness ( p = 0.016), even when close relationships were ignored ( p = 0.002). RR for third- and fifth-degree relatives developing VS were significantly elevated (RR, 60.83; p = 0.0005; 95% confidence interval [CI], 7.37-219.73) and (RR, 11.88; p = 0.013; 95% CI, 1.44-42.90), respectively. No VS-affected first-, second-, or fourth-degree relatives were observed. In the Utah Population Database population, no first- or second-degree relatives with VS were observed. RR for fifth-degree relatives developing VS was significantly elevated (RR, 2.23; p = 0.009; 95% CI, 1.15-3.90). These results provide strong evidence for an inherited predisposition to sporadic, unilateral VS. This study exhibits the value of genealogical resources with linked medical data for examining hypotheses regarding inherited predisposition. The high-risk unilateral VS pedigrees identified in two independent resources provide a powerful means of pursuing predisposition gene identification.

P03.01.A Late pseudoprogression of vestibular schwannoma after robotic guided stereotactic radiosurgery - Implications for follow-up

Abstract Background Stereotactic radiosurgery (SRS) may cause transient changes of morphology and volume in vestibular schwannomas (VS). This may lead to difficulties in distinguishing treatment-related changes (pseudoprogression) from tumor recurrence (true progression), especially at 12-24 months after treatment. Therefore, we investigated the time course of volume changes of VS after robot-guided SRS. Material and Methods We included all patients with unilateral VS who underwent single fraction robotic guided SRS using the Cyberknife® with a minimum follow-up (FU) of 24 months and MR images ≤3 mm slice thickness. Tumor volumes were measured on T1-weighted contrast enhanced images. Volume changes (percentage of tumor volume change compared to baseline) during FU were classified according to RANO criteria (“partial response” (PR) (≥65% decrease), “stable disease” (SD) (&amp;lt;65% decrease; &amp;lt;20% increase), or “progressive disease” (PD) (≥40% increase)). A new status “pseudoprogression” (PP) (&amp;gt;20% transient increase) was defined and divided into early (ePP, occurrence within first &amp;lt;12 months) and late (lPP, &amp;gt;12 months) PP. Results Overall 63 patients fulfilled the inclusion criteria. The median age was 56 years (range: 20-82) and the median initial tumor volume was 1.5 cm3 (range: 0.1 - 8.6). All patients received 13 Gy with an isodose level of 80%. The median radiological and clinical FU was 66 months (range: 24-103). We found PR in 36% (n=23), SD in 35% (n=22) and PP in 29% (n=18). The latter was separated in ePP in 16% (n=10) and lPP in 13% (n=8). The median time to peak in the ePP was six months (range: 4 - 10) and in the lPP 35 months (range: 14 - 61). The median time to return from peak to baseline was seven months in the ePP (range: 5 - 20) and 18 months (range: 6 - 33) in the lPP group. Using these criteria no PD was observed. Additionally, we did not find any significant impact of radiation parameters (coverage, nCi, prescription dose, maximal dose) or patient related parameters (tumor volume, age) on the onset of early and/or late PP. Conclusion In our study, we demonstrated that any volume increase assumed to be PD turned out to be ePP or lPP. This might impact the management of VS treated with robotic SRS during FU in favour of further observation.

P03.02.B Vestibular side effects following robotic guided stereotactic radiosurgery of vestibular schwannoma

Abstract Background New-onset vestibular disorders (VD), such as dizziness and imbalance, are common side effects after stereotactic radiosurgery (SRS) for vestibular schwannomas (VS). Although these symptoms can severely affect the daily life of VS patients, there are limited data available providing prognostic information on the risk of developing VD after SRS. Material and Methods We included patients who received Cyberknife® SRS for newly diagnosed unilateral VS between 2012 and 2015. The incidence of vestibular disorders before and after treatment was recorded and correlated with tumor, patient, and treatment characteristics. Results We identified 71 patients with a median age of 58 years (range: 21-82) and a median follow-up of 66 months (range: 3-105). Tumor volume before treatment was 1.5 cm3 ± 1.4 (range: 0.1-8.6). A mean marginal dose of 12.9 Gy ± 0.3 (range: 12-14) was administered, and all studied patients remained free of tumor recurrence. Forty-one (58%) of the patients had VD prior to SRS. Of the remaining 30 patients who did not have VD before treatment, 16 (53%) developed new VD (vertigo, n=4; balance disorders, n=8; mixture of VD, n=4). The median time to onset of symptoms was 6 months (range: 2-36). In most patients (n=11, 69%), the new symptoms completely resolved within a median time of 21 months (range: 1-63). In multivariate analysis, neither tumor volume (p=0.7), age (p=0.06), nor radiation dose (p=0.16) were significantly associated with the occurrence of VD. Conclusion In this cohort, about half of the patients develop new onset of transient VD after SRS. The incidence of VD after SRS was found to be independent from usual tumor-, patient- and treatment-related factors. Therefore, a detailed analysis of the dose exposure to the structures of the vestibular apparatus is recommended.

Matched Comparison of Hearing Outcomes in Patients With Vestibular Schwannoma Treated With Stereotactic Radiosurgery or Observation.

Previous studies comparing hearing outcomes in patients managed with stereotactic radiosurgery (SRS) and a watch-and-wait strategy were limited by small sample sizes that prevented controlling for potential confounders, including initial hearing status, tumor size, and age. To compare hearing outcomes for patients with vestibular schwannomas (VS) managed with observation and SRS while controlling for confounders with propensity score matching. Propensity score matching was used to compare 198 patients with unilateral VS with initial serviceable hearing (99 treated with SRS and 99 managed with observation alone) and 116 with initial class A hearing (58 managed with SRS and 58 with observation), matched by initial hearing status, tumor volume, age, and sex. Kaplan-Meier survival methods were used to compare risk of losing class A and serviceable hearing. Between patients with VS managed with SRS or observation alone, there was no significant difference in loss of class A hearing (median time 27.2 months, 95% CI 16.8-43.4, and 29.2 months, 95% CI 20.4-62.5, P = .88) or serviceable hearing (median time 37.7 months, 95% CI 25.7-58.4, and 48.8 months, 95% CI 38.4-86.3, P = .18). For SRS patients, increasing mean cochlear dose was not related to loss of class A hearing (hazard ratio 1.3, P = .17) but was associated with increasing risk of serviceable hearing loss (hazard ratio of 1.5 per increase in Gy, P = .017). When controlling for potential confounders, there was no significant difference in loss of class A or serviceable hearing between patients managed with SRS or with observation alone.

Rare tumor of internal auditory canal

Objective: To explore the clinical features and treatment strategy of rare tumor in the internal auditory canal(IAC). Methods: A retrospective study was carried out in 213 patients with lesion of ICA form January 2010 to December 2020. According to imaging features, surgical findings, and pathological diagnosis, there were 7 cases of non-sporadic acoustic neuroma, including 2 cases of cavernous hemangioma, 2 cases of aneurysm, 1 case of intralabyrinthical schwannoma, 1 case of meningioma, and 1 case of unilateral neurofibromatosis type 2 (NF2). The clinical manifestations, imaging data and intraoperative conditions as well as the formulation of individualized treatment strategies and prognosis were comprehensively analyzed. Results: In addition to hearing loss, cavernous hemangioma early appeared damage of facial nerve. CT showed expansion and calcification of IAC. Patients with aneurysm appeared tinnitus and vertigo early. CT showed enlargement of ampulla shape of IAC. DSA or MRA can help confirm the diagnosis. Patients with intralabyrinthine schwannoma early appeared refractory vertigo. High resolution MRI was helpful for diagnosis. "Dural tail sign" can be seen on enhanced MRI of meningeoma. Neurofibromatosis type 2 usually presented as bilateral vestibular schwannomas,but a few patients presented only with unilateral vestibular schwannomas.. All patients underwent labyrinth approach resection except one patient with NF2 for followed-up. Their postoperative symptoms were relieved. No tumor recurrence was observed during 6-3 years of follow-up. Conclusions: The clinical and imaging manifestations of rare tumors of the internal auditory canal are different. The principle of treatment is also different. It is helpful to avoid the serious consequences caused by blind operation to confirm diagnosis before operation.

A 2 and 5-Year Longitudinal Analysis of 671 Consecutive Patients Diagnosed with Unilateral Vestibular Schwannoma.

To analyse the 2 and 5-year outcomes of a cohort of patients with newly diagnosed vestibular schwannoma patients. Longitudinal cohort study. Tertiary skull base referral unit. Six hundred and seventy-one consecutive patients referred to the Cambridge Skull Base Unit between 2005 and 2010. 1) Treatment outcomes, 2) hearing preservation, 3) facial nerve function, and 4) gross tumor control. At initial diagnosis, 440/671(65.6%) of patients entered a watch, wait and rescan (WWR) pathway, 208/671 (31%) underwent primary microsurgical excision and 23/671 (3.4%) primary radiotherapy. Of patients who entered WWR, 144/440 (32.7%) exhibited tumor growth necessitating secondary intervention at a mean of 22.7 months; 67.4% had radiotherapy and 32.6% surgery. Radiotherapy was successful at achieving tumor control in 95% of cases. Primary surgery via the translabyrinthine route was performed in the majority of cases allowing for a radiologically clear surgical resection in 93% of cases. The Cambridge philosophy of treating the newly diagnosed vestibular schwannoma aims at preserving functional status where possible. In patients with small tumors it is recommended that they are placed on to a WWR pathway, of which 67.3% will not exhibit any growth by 5 years. If small tumors grow more than 2 mm by serial scanning, radiotherapy offers a high rate of tumor control. In patients with larger tumors more than 20 mm we would advocate microsurgical excision by the translabyrinthine route which offers excellent functional outcomes and gross tumor control.