Neurocognition After Radiotherapy in CNS- and Skull-base Tumors

Not Applicable

Recruiting

• Conditions: Meningioma; Glioma; Brain Tumor; Magnetic Resonance Imaging; Pituitary Adenoma; Cognition
• Interventions: Diagnostic Test: MRI; Other: Toxicity scoring

• Registration Number: NCT05727605
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

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)

Study Timeline

• Study First Submitted: 2023-01-13
• Study First Submitted QC: 2023-02-03
• Study Start: 2023-02-08
• Study First Posted: 2023-02-14
• Status Verified: 2024-04
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-08
• Primary Completion: 2026-02-01
• Study Completion: 2027-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Primary brain and skull-base tumors	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
Primary brain and skull-base tumors	Toxicity scoring	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

Primary Outcome Measures

Name	Time	Method
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)	2 years
Development of a Normal Tissue Complication Probability model (NTCP-model) for each cognitive domain (memory, executive functioning, attention and language)	4 years	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

Secondary Outcome Measures

Name	Time	Method
Early (3 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)	4 years	Changes on advanced MR imaging at 3 months post-RT compared to baseline
Late (12 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)	4 years	Changes on advanced MR imaging at 12 months post-RT compared to baseline

Trial Locations

Locations (3)

University Hospitals Ghent; 🇧🇪 Gent, Belgium

Gasthuis Zusters Antwerpen; 🇧🇪 Wilrijk, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium