Vestibular Schwannoma - Radiosurgery or Expectation: V-REX. (V-REX)

Study design and purpose:

Design: Randomised study blinded to observer on primary endpoint (tumor volume). Intention-to-treat, ie patients who cross over from conservative to GKRS group during the study period are assigned to their original group. Patients who refrain from radiosurgery despite randomisation are assigned to radiosurgery group.

Purpose: compare the treatment of small and medium-sized VS treated with a standardised dose of 12 Gy to the tumor periphery with expectative treatment.

Primary endpoint:

Growth measured as volume ratio V4years/Vbaseline and 1/volume doubling time, evaluated by T1 contrast MRI volumetry at one, two, three and four years.

Secondary endpoints:

Hearing acuity according to Gardner Robertson scale at four years (safety endpoint).

Conversion to other treatment during study period Adverse effects

Subjective complaints assessed by questionnaires:

Penn Vestibular Schwannoma QOL Scale EQ-50 Scale

Investigations:

Prior to inclusion: MRI less than 6 months showing VS.

After inclusion and at 1,2 3,4 years, all at study site:

MRI of inner ear (acoustic neuroma protocol) Balance platform Nystagmometry Audiometry

Effect registration:

Main variable:

Tumor volume, measured on a T1 contrast MRI scan with 2mm slice interval/thickness. For study, the measurement is to be done by a blinded observer.

Economy. Costs associated with study are financed by research donations from Helse-Vest and The National Center for Vestibular Schwannomas.

Radiology: Image based tumor volumes As the primary endpoint is relative tumor size, an accurate measure of tumor volume and changes thereof, is mandatory. This will be obtained using a state-of-the-art magnetic resonance imaging (MRI) system suited for acquiring high resolution (1mm3), three dimensional (3D) anatomical images. A 1.5T imaging system which meets the required field homogeneity will be used for imaging. The image contrast will be T1 weighted with gadolinium based contrast agent, yet a T2 weighted image volume will also be included (preferably also acquired in 3D). An identical imaging protocol will be acquired at each time point (prior to randomization, on site follow up, 4-year annual follow up), and image slices will be positioned according to anatomical landmarks in each patients to minimize variability across time. All 3D acquisitions will be performed with sagittal slicing to minimize artifacts, but will also be reformatted into coronal and axial views (1mm slice thickness, no gap between slices) on the scanner system.

The subsequent imaging processing, i.e. the estimation of tumor volume and longitudinal changes thereof, will be performed using available software at time of analysis.

Study schedule

Clinical examination, MRI, Questionnaires, Audiometry, Vestibular tests are done at baseline and then annually for 4 years. Patients randomised for radiosurgery are treated within 3 months after baseline.