Neurocognition After Radiotherapy in CNS- and Skull-base Tumors

Neurocognition After Radiotherapy in Adult Brain and Base of Skull Tumors

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)

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:

  • Incompletely resected IDH-wild-type glioma
  • Completely resected IDH-wild-type and MGMT-promotor unmethylated 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 previously treated by chemo and/or radiation therapy

• Genetic syndrome (e.g. Down)

• Unable to perform MR imaging (claustrophobia, metallic implants like pacemaker/ICD/neurostimulator)