Neurocognition After Radiotherapy in CNS- and Skull-base Tumors

NCT ID: NCT05727605

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-08
• Study Completion Date: 2027-02-01

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)

Conditions

Cognition; Brain Tumor; Magnetic Resonance Imaging; Meningioma; Glioma; Pituitary Adenoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Primary brain and skull-base tumors

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

Group Type: OTHER

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

Intervention Type: BEHAVIORAL

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

MRI

Intervention Type: DIAGNOSTIC_TEST

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

Questionnaires: EORTC QLQ C30 & BN20, STAI, CFQ, BDI-II, BRIEF-A, FACIT-F, PSQI

Intervention Type: BEHAVIORAL

Time points: baseline, 12 months post-radiotherapy and 24 months post-radiotherapy

Toxicity scoring

Intervention Type: OTHER

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

Interventions

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

Intervention Type: BEHAVIORAL

MRI

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

Intervention Type: DIAGNOSTIC_TEST

Questionnaires: EORTC QLQ C30 & BN20, STAI, CFQ, BDI-II, BRIEF-A, FACIT-F, PSQI

Time points: baseline, 12 months post-radiotherapy and 24 months post-radiotherapy

Intervention Type: BEHAVIORAL

Toxicity scoring

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

Intervention Type: OTHER

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: collaborator

Gasthuis Zusters Antwerpen

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maarten Lambrecht, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

University Hospitals Ghent

Ghent, , Belgium

Site Status: RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

Gasthuis Zusters Antwerpen

Wilrijk, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Laurien De Roeck, MD

Role: CONTACT

Laurien.deroeck@uzleuven.be

016 34 76 00

Maarten Lambrecht, MD PhD

Role: CONTACT

Maarten.lambrecht@uzleuven.be

016 34 76 00

Facility Contacts

Tom Boterberg, MD PhD

Role: primary

Maarten Lambrecht, MD PhD

Role: primary

Katrien Erven, MD PhD

Role: primary

Other Identifiers

S65664

Identifier Type: -

Identifier Source: org_study_id