Neurocognition After Radiotherapy in CNS- and Skull-base Tumors (NARCiS)

The goal of this multicenter prospective longitudinal study is to study the long-term impact of multimodal treatment (chemotherapy, radiotherapy and surgery) in adult brain and base of skull tumors on neurocognitive functioning. All included patients will complete a self-report inventory (subjective cognitive functioning, QoL, confounders), a cognitive test battery, an advanced MR at multiple timepoints. Moreover, toxicity will be scored according to the CTCAEv5.0 in these patients over time.

This study will combine MR imaging techniques together with elaborate neuropsychological assessments and RT dosimetry in 120 patients who will be examined baseline (before RT) and followed longitudinally after RT. The first objective is to build an NTCP model for neurocognitive decline after RT (for each cognitive domain separately), linking dose-volume parameters to structures within the brain susceptible to neurological damage and neurocognitive decline after radiotherapy. These NTCP models can be used to make predictions on neurocognitive decline in future primary brain tumour patients receiving cranial RT. The second objective is to evaluate dose-dependent neurocognitive decline. In particular, the investigators will assess: Prevalence and severity of neurocognitive decline after RT for all cognitive domains Brain structures or functional brain connections important in neurocognitive functioning (based on dedicated MRI). Dose-dependencies of specific neurocognitive skills after RT in adult brain tumour patients Correlations between RT dosimetry and early brain changes (MRI)

Primary brain and skull-base tumors who are amenable for radiotherapy (photon or proton therapy) will all be examined with neurocognitive tests, questionnaires and advanced MR imaging

Neurocognitive tests: WAIS digit span, HVLT-R, COWAT, MOCA, WAIS digit symbol substitution, TMT A&B, Stroop Color Word Test

Primary brain tumour patients will be evaluated longitudinally at the following timepoints: baseline (minimal 4 weeks after surgery, before radiotherapy), three months after end of radiotherapy, 1 year after end of radiotherapy and 2 years after end of radiotherapy. At each visit, neurocognitive testing, a self-report inventory and/or advanced MR imaging will take place. Time points: baseline, 12 months post-radiotherapy and 24 months post-radiotherapy

Advanced MRI: all participants will be scanned on a 3T Siemens of Philips MR scanner (multicenter protocol): MPRAGE, FLAIR, T2, DWI, rsfMRI, SWI & ASL Time points: baseline, 3 months post-radiotherapy and 12 months post-radiotherapy

During and after radiotherapy and at at the end of the study, adverse events will be monitored using CTCAEv5.0.

Prevalence of neurocognitive decline (changes in z-scores) compared to baseline at one year post-radiotherapy, for all cognitive domains (memory, executive functioning, attention and language)

Development of a Normal Tissue Complication Probability model (NTCP-model) for each cognitive domain (memory, executive functioning, attention and language)

Construct NTCP models to predict neurocognitive decline based on RT dosimetric and other explanatory variables (gender, age at diagnosis, comorbidities, level of education, social factors such as social activity and occupation, tumour size and localization, pathological/genetic/molecular characteristics, therapy protocols (surgery, radiotherapy and/or chemotherapy)) in an NTCP model for each cognitive domain

Early (3 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)

Late (12 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)

Inclusion Criteria: Adult patients (≥ 18 years at the time of diagnosis) with a primary brain or base of skull tumour, who are amenable for conventionally fractionated radiotherapy (photon or proton irradiation) Exclusion Criteria: Patients with tumours with poor prognostic characteristics (e.g. IDH1/2 wild type glioma, grade III meningioma, H3K27M midline glioma) Patients with tumours requiring craniospinal irradiation (CSI)/whole ventricular irradiation (WVI) Hypofractionated/stereotactic radiation (fraction sizes > 2 Gy per fraction) Inability to perform the cognitive tests or self-report inventories because of motor/sensory deficits or insufficient Dutch language proficiency Mental retardation documented before diagnosis Pre-diagnosis/pre-existing psychiatric diagnosis resulting in cognitive deficits like psychoses, neurodevelopmental disorders (autism/learning disorders) Relapse priory treated by chemo and/or radiation therapy Genetic syndrome (e.g. Down) Unable to perform MR imaging (claustrophobia, metallic implants like pacemaker/ICD/neurostimulator)