Neurocognition After Radiotherapy in CNS- and Skull-base Tumors

Glioma Clinical Trial

— NARCiS  

Official title:

Neurocognition After Radiotherapy in Adult Brain and Base of Skull Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05727605
• Other study ID #: S65664
• Status: Recruiting
• Phase: N/A
• Start date: February 8, 2023
• Est. completion date: February 1, 2027

Study information

• Verified date: April 2024
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Laurien De Roeck, MD
• Phone: 016 34 76 00
• Email: Laurien.deroeck[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: February 1, 2027
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenoma
• Brain Tumor
• Cognition
• Glioma
• Magnetic Resonance Imaging
• Meningioma
• Pituitary Adenoma
• Pituitary Neoplasms

Intervention

Behavioral:
• 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

Diagnostic Test:
• 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

Behavioral:
• 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

Other:
• Toxicity scoring
During and after radiotherapy and at at the end of the study, adverse events will be monitored using CTCAEv5.0.

Locations

Country	Name	City	State
Belgium	University Hospitals Ghent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Gasthuis Zusters Antwerpen	Wilrijk

Sponsors (3)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	Gasthuis Zusters Antwerpen, University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	4 years
Secondary	Early (3 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)	Changes on advanced MR imaging at 3 months post-RT compared to baseline	4 years
Secondary	Late (12 months post-radiotherapy) changes identified on structural and functional MR imaging (graph measures)	Changes on advanced MR imaging at 12 months post-RT compared to baseline	4 years