Clinical trial NCT05727605: Neurocognition After Radiotherapy in CNS- and Skull-base Tumors
Official title: Neurocognition After Radiotherapy in Adult Brain and Base of Skull Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cognition
Brain Tumor
Magnetic Resonance Imaging
Meningioma
Glioma
Pituitary Adenoma
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Gasthuis Zusters Antwerpen
First posted: 2023-02-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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)

Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: 2 years
measure: Development of a Normal Tissue Complication Probability model (NTCP-model) for each cognitive domain (memory, executive functioning, attention and language)
timeFrame: 4 years
Secondary outcomes:
measure: Early (3 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)
timeFrame: 4 years
measure: Late (12 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)
timeFrame: 4 years
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospitals Ghent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Wilrijk
country: Belgium
facility: Gasthuis Zusters Antwerpen
Study officials:
affiliation: UZ Leuven
name: Maarten Lambrecht, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: