Neurocognition After Radiotherapy in CNS- and Skull-base Tumors (NARCiS)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Pituitary Adenoma; Brain Tumor; Magnetic Resonance Imaging; Meningioma; Cognition
• Intervention / Treatment: Behavioral: Neurocognitive tests: WAIS digit span, HVLT-R, COWAT, MOCA, WAIS digit symbol substitution, TMT A&B, Stroop Color Word Test; Diagnostic test: MRI; Behavioral: Questionnaires: EORTC QLQ C30 & BN20, STAI, CFQ, BDI-II, BRIEF-A, FACIT-F, PSQI; Other: Toxicity scoring

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • Recruiting
    • University Hospitals Ghent
  • Leuven, Belgium
    • Recruiting
    • UZ Leuven
  • Wilrijk, Belgium
    • Recruiting
    • Gasthuis Zusters Antwerpen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 (e.g. IDH1/2 wild type 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 priory 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: University Hospital, Ghent; Gasthuis Zusters Antwerpen

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): February 1, 2027

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms, Nerve Tissue; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Pituitary Diseases; Meningeal Neoplasms; Adenoma; Pituitary Neoplasms; Meningioma
• Other Study ID Numbers: S65664

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No