Vestibular Tests Related to Tumor Volume in 137 Patients With Small to Medium-Sized Vestibular Schwannoma

Objective: The video head impulse test (vHIT) and cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) are new methods for measuring peripheral vestibular function. The objectives of this study were to compare these tests and the traditionally used caloric test in patients with small and medium-sized untreated vestibular schwannoma (VS) and to measure the correlation between the tests' results and tumor volume. Study Design: National cross-sectional study. Setting: Tertiary university clinic. Methods: Prevalence of abnormal cVEMP, oVEMP, caloric test, and 6-canal vHIT results on the tumor side and the nontumor side were compared and related to tumor volume with regression analyses in 137 consecutive VS patients assigned to a wait-and-scan protocol in the period 2017 to 2019. Results: The sensitivity of 6-canal vHIT, caloric test, cVEMP, and oVEMP to detect vestibulopathy in VS patients was 51%, 47%, 39%, and 25%, respectively. Normal tests were found in 21% of the patients. The results of vHIT and caloric test were related to tumor volume, but this was not found for cVEMP and oVEMP. Conclusion: The caloric test and 6-canal vHIT showed the highest sensitivity in detecting vestibulopathy in untreated VS patients. vHIT, and particularly the posterior canal, was limited with a high prevalence of abnormal results on the nontumor side. A combination of cVEMP and caloric test was favorable in terms of a relatively high sensitivity and low prevalence of abnormal results on the nontumor side. Larger tumors had a higher rate of pathology on caloric testing and vHIT.publishedVersio

Clinical Management of Vestibular Schwannoma : The V-REX randomized trial and other clinical studies on vestibular schwannoma

Introduksjon: Vestibularis schwannomer (VS) er godartede svulster som utgår fra de Schwannske cellene rundt den åttende hjernenerven og utgjør ca. 8% av alle intrakranielle neoplasmer. Behandlingsalternativene er mikrokirurgisk reseksjon, stereotaktisk strålekniv eller en aktiv overvåkningsstrategi med regelmessige kliniske og radiologiske kontroller. Hvilken behandlingsmodalitet som er best er omdiskutert, og det foreligger ingen randomiserte studier som kan indikere en entydig overlegen strategi. Hensikt: Å undersøke effekten av strålekniv ved nydiagnostiserte små og mellomstore VS; å undersøke effekten av strålekniv som adjuvant terapi etter mikroskirurgisk reseksjon av store VS; å forstå det naturlige forløpet av tilstanden hva gjelder symptomutvikling og livskvalitet. Metoder: Prosjektet inkluderer en blindet randomisert kontrollert studie og tre non-randomiserte kontrollerte studier. Studiene ble gjennomført ved Nasjonal Behandlingstjeneste for Vestibularisschwannomer ved Haukeland Universitetssykehus i samarbeid med Mayo Clinic Rochester. Tilsammen, har 500 pasienter og 49 kontroller deltatt. Alle tre behandlingsmodaliteter er studert, og deltakerne gjennomgikk kliniske kontroller, audiovestibulære tester, radiologisk evaluering og besvarte en rekke standardiserte spørreskjema. Resultater: Stereotaktisk strålekniv som primærbehandling var overlegen en konservativ tilnærming hva gjelder tumorvolumreduksjon i små og mellomstore VS, men var ikke forbundet med bedre hørsel, vestibulær funksjon, livskvalitet eller risiko for rebehandling. En multimodal tilnærming med mikrokirurgisk subtotal reseksjon og adjuvant stereotaktisk strålekniv i store VS gir tilfredsstillende tumorkontroll uten å kompromittere ansiktsnervens funksjon. VS pasienter lider av betydelig utmattelse, et symptom som er sterkt assosiert med nedsatt livskvalitet.Introduction: Vestibular schwannomas (VS) are benign tumors arising from the Schwann cells of the eighth cranial nerve and account for 8% of all intracranial neoplasms. Contemporary management options include microsurgical resection, stereotactic radiosurgery, and an observational wait-and-scan approach. The optimal treatment for vestibular schwannomas remains controversial, and there is no high-level evidence indicating that one strategy is unequivocally superior to the others. Objective: To investigate the effect of radiosurgery in newly-diagnosed small to medium-sized VS; the effect of salvage radiosurgery following microsurgical resection in large VS; and the natural course of symptoms and quality of life. Methods: The project encompasses an observer-blinded randomized controlled trial and three non-randomized controlled studies, all conducted at The Norwegian National Unit for Vestibular Schwannoma. One study was a collaboration with the Mayo Clinic. In total, 500 patients and 49 controls participated. All three treatment modalities were studied, and participants underwent clinical examination, audiovestibular tests, radiographic evaluation, and responded to questionnaires. A particular methodological feature of this project is the acquisition of tumor volume measurements on more than 2000 scans. Results: Upfront radiosurgery was superior to wait-and-scan regarding tumor volume in small and medium-sized VS but did not demonstrate benefits regarding hearing, vestibular function, quality of life, or risk of salvage treatment. A multimodality approach of initial microsurgical subtotal resection and adjuvant stereotactic radiosurgery in large VS provides acceptable tumor control rates without compromising facial nerve outcomes. VS patients suffer from significant fatigue, a symptom strongly associated with reduced quality of life.Doktorgradsavhandlin

Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma

Introduction Ionizing radiation is a known etiologic factor in tumorigenesis and its role in inducing malignancy in the treatment of vestibular schwannoma has been debated. The purpose of this study was to identify a copy number aberration (CNA) profile or specific CNAs associated with radiation exposure which could either implicate an increased risk of malignancy or elucidate a mechanism of treatment resistance. Methods 55 sporadic VS, including 18 treated with Gamma Knife Radiosurgery (GKRS), were subjected to DNA whole-genome microarray and/or whole-exome sequencing. CNAs were called and statistical tests were performed to identify any association with radiation exposure. Hierarchical clustering was used to identify CNA profiles associated with radiation exposure. Results A median of 7 (0–58) CNAs were identified across the 55 VS. Chromosome 22 aberration was the only recurrent event. A median aberrant cell fraction of 0.59 (0.25–0.94) was observed, indicating several genetic clones in VS. No CNA or CNA profile was associated with GKRS. Conclusion GKRS is not associated with an increase in CNAs or alteration of the CNA profile in VS, lending support to its low risk. This also implies that there is no major issue with GKRS treatment failure being due to CNAs. In agreement with previous studies, chromosome 22 aberration is the only recurrent CNA. VS consist of several genetic clones, addressing the need for further studies on the composition of cells in this tumor

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