Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial.

Importance: Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. Objective: To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. Design, Setting, and Participants: Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021. Interventions: Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. Main Outcomes and Measures: The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. Results: Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. Conclusion and relevance: Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02249572.

Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study.

INTRODUCTION: The optimal management of small-sized to medium-sized vestibular schwannoma (VS) is a matter of controversy. Clinical results of the prevailing treatment modalities (microsurgery, stereotactic radiosurgery (SRS), and conservative management (CM)) are documented, but comparative studies are few, and none are randomised or blinded. Upfront radiosurgery, or a careful follow-up by MRI with subsequent treatment on growth, are two strategies used at many centres. The present study aims at comparing these strategies by randomising individuals with newly diagnosed tumours to either upfront SRS or initial CM. METHODS AND ANALYSIS: The Vestibular Schwannoma: Radiosurgery or Expectation study is designed as a randomised, controlled, observer-blinded, single-centre superiority trial with two parallel groups. Eligible patients will be randomised using sequentially numbered opaque sealed envelopes, and the radiosurgery group will undergo standard Gamma Knife Radiosurgery (GKRS) within 2 months following randomisation. The primary endpoint is tumour growth measured as volume ratio V4years/Vbaseline and volume doubling time, evaluated by annual T1 contrast MRI volumetric analysis. Secondary endpoints include symptom and sign development measured by clinical examination, audiovestibular tests, and by patient's responses to standardised validated questionnaires. In addition, the patient's working status, and the health economics involved with both strategies will be evaluated and compared. All outcome assessments will be performed by blinded observers. Power analysis indicates that 100 patients is sufficient to demonstrate the effect of GKRS on tumour volume. ETHICS AND DISSEMINATION: The trial has ethical approval from the Regional Ethical Committee (23503) and funding from The Western Norway Regional Health Authority. Trial methods and results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical trials: NCT02249572. Haukeland University Hospital record: 2014/314. Regional Ethical Committee (REC West): 23 503. The Western Norway Regional Health Authority: 912 281.

Fatigue in patients with vestibular schwannoma.

BACKGROUND: Patients with vestibular schwannoma (VS) often complain about tiredness, exhaustion, lack of energy, and strength, but such symptoms of fatigue have scarcely been objectified and analyzed in a VS population. We aimed to characterize fatigue in a cohort of patients with VS and compare such symptoms with a control group. METHODS: All patients who attended an educational course for patients with VS were surveyed with validated tools for assessment of fatigue (fatigue severity scale), anxiety and depression (hospital anxiety and depression scale), sleepiness (Epworth sleepiness scale), and apathy (Starkstein apathy scale). Quality of Life was assessed with the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL). Symptom severity was estimated with a visual analog scale (VAS). The results have been compared to a control group consisting of patient companions. RESULTS: Data from 88 VS patients and 49 controls were analyzed. The controls had similar age and sex distribution as patients. Fifty-seven percent of VS patients had significant fatigue, compared to 25% in the control group. The mean fatigue score was 4.1 for the patients, and 2.8 for controls. Patients with fatigue were more likely to have depression, anxiety, sleepiness, and apathy. No correlation of fatigue was found with age, gender, or treatment modality. Regression analyses revealed depression, apathy, and vertigo to be predictors of fatigue. Fatigue was strongly correlated to QoL. CONCLUSION: Almost six out of ten VS patients had fatigue, significantly higher than the control group. Interest and focus on fatigue in VS patients can improve the patient's QoL.

Long-term Effects of Conservative Management of Vestibular Schwannoma on Dizziness, Balance, and Caloric Function.

OBJECTIVES: To study the development of dizziness, caloric function, and postural sway during long-term observation of untreated vestibular schwannoma patients. STUDY DESIGN: Retrospective review of a prospectively maintained longitudinal cohort. SETTING: Tertiary referral hospital. SUBJECTS AND METHODS: Patients with vestibular schwannoma undergoing wait-and-scan management were included-specifically, those who did not require treatment during a minimum radiologic follow-up of 1 year. Baseline data and follow-up included magnetic resonance imaging, posturography, bithermal caloric tests, and a dizziness questionnaire. Main outcomes were prevalence of moderate to severe dizziness, canal paresis, and postural instability at baseline and follow-up, as compared with McNemar's test. RESULTS: Out of 433 consecutive patients with vestibular schwannoma, 114 did not require treatment during follow-up and were included. Median radiologic follow-up was 10.2 years (interquartile range, 4.5 years). Age ranged from 31 to 78 years (mean, 59 years; SD, 10 years; 62% women). Median tumor volume at baseline was 139 mm3 (interquartile range, 314 mm3). This did not change during follow-up (P = .446). Moderate to severe dizziness was present in 27% at baseline and 19% at follow-up (P = .077). Postural unsteadiness was present in 17% at baseline and 21% at follow-up (P = .424). Canal paresis was present in 51% at baseline and 56% at follow-up (P = .664). CONCLUSIONS: There was no significant change in the prevalence of dizziness, postural sway, or canal paresis during conservative management of vestibular schwannoma, while tumor volume remained unchanged. This indicates a favorable prognosis in these patients with regard to vestibular symptoms.

Long-term quality of life in patients with vestibular schwannoma: an international multicenter cross-sectional study comparing microsurgery, stereotactic radiosurgery, observation, and nontumor controls.

OBJECT: The optimal treatment for sporadic vestibular schwannoma (VS) is highly controversial. To date, the majority of studies comparing treatment modalities have focused on a narrow scope of technical outcomes including facial function, hearing status, and tumor control. Very few publications have investigated health-related quality of life (HRQOL) differences between individual treatment groups, and none have used a disease-specific HRQOL instrument. METHODS: All patients with sporadic small- to medium-sized VSs who underwent primary microsurgery, stereotactic radiosurgery (SRS), or observation between 1998 and 2008 were identified. Subjects were surveyed via postal questionnaire using the 36-Item Short Form Health Survey (SF-36), the 10-item Patient-Reported Outcomes Measurement Information System short form (PROMIS-10), the Glasgow Benefit Inventory (GBI), and the Penn Acoustic Neuroma Quality-of-Life (PANQOL) scale. Additionally, a pool of general population adults was surveyed, providing a nontumor control group for comparison. RESULTS: A total of 642 respondents were analyzed. The overall response rate for patients with VS was 79%, and the mean time interval between treatment and survey was 7.7 years. Using multivariate regression, there were no statistically significant differences between management groups with respect to the PROMIS-10 physical or mental health dimensions, the SF-36 Physical or Mental Component Summary scores, or the PANQOL general, anxiety, hearing, or energy subdomains. Patients who underwent SRS or observation reported a better total PANQOL score and higher PANQOL facial, balance, and pain subdomain scores than the microsurgical cohort (p < 0.02). The differences in scores between the nontumor control group and patients with VS were greater than differences observed between individual treatment groups for the majority of measures. CONCLUSIONS: The differences in HRQOL outcomes following SRS, observation, and microsurgery for VS are small. Notably, the diagnosis of VS rather than treatment strategy most significantly impacts quality of life. Understanding that a large number of VSs do not grow following discovery, and that intervention does not confer a long-term HRQOL advantage, small- and medium-sized VS should be initially observed, while intervention should be reserved for patients with unequivocal tumor growth or intractable symptoms that are amenable to treatment. Future studies assessing HRQOL in VS patients should prioritize use of validated disease-specific measures, such as the PANQOL, given the significant limitations of generic instruments in distinguishing between treatment groups and tumor versus nontumor subjects.

Working disability in Norwegian patients with vestibular schwannoma: vertigo predicts future dependence.

OBJECTIVE: We examined whether reduced hearing, tinnitus, dizziness, and unsteadiness affected the patients' ability to maintain work within a time frame of 2-10 years after diagnosis. METHODS: A total of 434 consecutive patients were followed at regular intervals. Data on symptoms were scored prospectively and dichotomized by visual analog scales for tinnitus and vertigo. Study design is retrospective. Hearing acuity was scored according to the Gardner-Robertson scale, and unsteadiness was measured on a balance platform. Patients were asked about working status, and scored as receiving governmental compensation for disability. RESULTS: Two hundred six patients were eligible for study. Of these, one died and nine were lost to follow-up. Ninety-seven patients received conservative management, 49 patients recieved gamma knife radiosurgery, and 50 patients were treated by microsurgery. Mean follow-up time was 58.7 months (range, 20-132 months). There was a significant increase in the number of individuals receiving compensation during the study period (P < 0.0001). At baseline, the proportion of pension receivers was within same range as that of the age- and sex-matched Norwegian population (5.61% vs. 6.91%; case-control odds ratio, 0.82; 95% confidence interval 0.45-1.49; P = 0.51, not significant). At the final time point, the increase in the number of receivers deviated significantly from the reference population (case-control odds ratio, 3.80; 95% confidence interval 2.71-5.33; P ≤ 0.001). Examining symptoms at first presentation as predictors of future dependence revealed that vertigo and higher mean age were associated with a higher risk (P < 0.001 and P = 0.015, respectively). No other symptoms were predictive of dependence. CONCLUSIONS: In a prospectively followed cohort of Norwegian patients with vestibular schwannoma, vestibular complaints were significant predictors for becoming dependant of disability pension.