Prospective Evaluation of Vestibular Schwannoma Irradiation

Vestibular schwannomas (VS) are benign nerve sheath tumors arising in the
cerebellopontine angle, in between the petrous bone and the brainstem. Early
symptoms comprise hearing loss, dizziness and/or unsteadiness and tinnitus.
Most people are initially managed with an active surveillance protocol,
comprising control for tumor growth through regular MRI-scans. Large or growing
tumors are treated by radiotherapy or a surgical resection, with tumor control
rates between 90-100%. Because patients have a normal life expectancy with
timely intervention, maintaining functions and quality of life are of paramount
importance in vestibular schwannoma treatment.
This study will look at the prevalence and longitudinal changes of
hearing loss and objective and subjective cognitive problems in patients
undergoing treatment with radiotherapy for vestibular schwannoma. Cognitive
functioning is a complex and dynamic system. In vestibular schwannoma patients
it could be affected in multiple ways: by the tumor causing pressure on
adjacent (brain) structures, secondary to symptoms (as tinnitus,
hearing/balance impairment, mood disorder), because of the treatment itself
(radiotherapy/surgery), and perhaps through other pathways still unknown. There
is one previous study on cognitive testing prior to vestibular schwannoma
surgery, which found multiple cognitive domains affected in their patient
population.
Hearing loss has been associated with cognitive impairment, even when
the hearing loss is subclinical. To maintain optimal understanding, listeners
with hearing loss must allocate more cognitive resources to speech processing
than listeners without hearing loss. Research further suggests that the
sustained cognitive effort required to offset auditory degradation due to
hearing loss may lead to subjective reports of mental fatigue. In addition to
hearing loss, VS patients also experience tinnitus and balance problems. These
symptoms may influence patients in a similar way as hearing loss does (by
shifting more resources from other ongoing cognitive tasks and increasing
fatigue). Mood disorders, such as anxiety and depression, also can have an
effect on cognition and cognitive test results. For radiotherapy, there is
growing evidence for cognitive alterations after brain irradiation. This can
already occur at low radiation dosages (as described mainly in animal models).
To better understand and/or predict the overall cognitive status and changes,
possible MR imaging biomarkers are studied. For this study, the aim will be to
qualitatively describe the difference in MRI brain function over time, and
explore the correlation to treatment, symptomology, and subjective and
objective cognitive functioning.

Primary Objectives:
• To evaluate the subjective and objective cognitive complaints and cognitive
function in patients receiving radiotherapy for their vestibular schwannoma.
Secondary objectives:
• To explore the use of (MRI) imaging biomarkers for cognitive and/or neuronal
changes over time.
• To report treatment outcomes and radiation-induced toxicity (e.g. hearing
deterioration, dizziness and/or unsteadiness) from a prospective observational
cohort of vestibular schwannoma patients.
• To compare the group receiving radiotherapy to a control group without any
active treatment for their vestibular schwannoma.
• To theoretically compare radiotherapy treatment plans of two different
modalities (photon and proton radiotherapy) of the included patients.
• To compare and validate two adjusted cognitive tests (focused on balance and
hearing) in vestibular schwannoma patients and healthy individuals.

Prospective, observational cohort study with invasive measurement.

The time of the additional diagnostics are the largest burden of this study.
The risk is assessed as being low. The patient can have discomfort
(claustrophobia, injection of contrast) or risk (allergy chance < 0,01%) from
the MRIs.