PREselection of Patients at Risk for COgnitive DEcline After Radiotherapy Using Advanced MRI

Meningioma are slow growing and frequently occurring intracranial tumors, responsible for 33% of all asymptomatic intracranial tumors and 13-26% of all symptomatic primary brain tumors. The 10-year survival rate is 72%. A variety of treatment options is available for symptomatic meningioma including surgical removal with or without radiotherapy or radiotherapy alone. These therapies can have negative impact on cerebral functioning.

After high dose radiotherapy for primary or metastatic brain tumors 50-90% of > 6 months' survivors develop irreversible disabling cognitive decline leading to premature loss of independence, reduced Quality of Life (QOL) as well as significant economic burden both at the individual as societal level. Especially for patients with a good prognosis like benign meningioma, maintaining neurocognitive function is crucial. Understanding the mechanisms underlying radiation induced cognitive decline is complex and which brain areas to spare are an important subject of research.

Evaluation methods to assess cognitive function and predict cognitive decline are urgently needed, this will allow the development of optimized treatment strategies with the aim to preserve or even improve cognitive function in meningioma patients. Improvements in the field of neuroimaging techniques (i.e. advanced MRI techniques) have the possibility to identify areas susceptible to cognitive impairment. This allows in the future a more personalized radiation treatment by identifying patients at risk, by optimizing the radiotherapy dose to specific brain regions, that could eventually reduce or prevent, cognitive decline. Improvements in the field of radiotherapy for example by higher precision treatment such proton therapy have potential in obtaining these more individualized strategies.

Study Overview

• Status: Recruiting
• Conditions: Meningioma
• Intervention / Treatment: Other: PRECODE-MRI

• Study Type: Observational
• Enrollment (Anticipated): 67

Contacts and Locations

• Study Contact: Name: Danielle Eekers; Phone Number: +31884455600; Email: danielle.eekers@maastro.nl
• Study Contact Backup: Name: Karen Zegers; Phone Number: +31884455600; Email: karen.zegers@maastro.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Recruiting
      • Maastricht Radiation Oncology
      • Contact: Danielle Eekers; Phone Number: +31884455600; Email: danielle.eekers@maastro.nl
      • Contact: Karen Zegers; Phone Number: +31884455600; Email: karen.zegers@maastro.nl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult (18 years or older) patients with meningioma tumours (WHO I) in a good clinical condition treated with curative intend using radiotherapy (proton or photon) without other known malignancies.

Description

Inclusion Criteria:

• Meningioma WHO I, grading based on pathology or radiological features
• Age ≥ 18 years.
• Karnofsky Performance Score 70 or above.
• Ability to comply with the protocol, including neuropsychological testing and imaging.
• Ability to understand the requirements of the study and to give written informed consent, as determined by the treating physician.
• Written informed consent.

Exclusion Criteria:

• Resection meningioma < 3mnd
• Age < 18 years
• Pregnancy
• Any prior cranial radiotherapy
• Any prior chemotherapy in the last 5 years
• Contra-indication for MR imaging (i.e. metal implants, claustrophobia)
• Any other serious medical condition that could interfere with follow-up.
• Severe aphasia or language barrier interfering with assessing endpoints (i.e. completion of questionnaires or neurocognitive performance)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation cognitive failure and radiotherapy dose	Correlation between the delta cognitive failure score (baseline vs 2 years) and radiotherapy dose in cognition related brain regions (supratentorial brain, hippocampus left/right and anterior/posterior, cerebellum anterior/posterior).	2 years after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation baseline imaging and patient specific parameters	Correlation between baseline imaging (advanced MRI sequence) and patient specific parameters (e.g. baseline cognitive status, age, Karnofsky index (KPS), co-morbidity, alcohol consumption, smoking, medication)	2 years after radiotherapy
RT induced cognitive change measured with extensive cognitive testing	RT-induced cognitive change measured with extensive cognitive testing	2 years after radiotherapy
Correlation advanced MRI and PROMS	Correlation of advanced MRI and treatment/dose parameters to PROMS; EQ/5D, QLQ/C30, QLQ/BN20, Cognitive Failure questionnaire (CFQ) , Multidimentional Fatigue Index (MVI/20)	2 years after radiotherapy
Radiation susceptibility of organs by Normal Tissue Complication Probability (NTCP)	Identification of radiation susceptibility of individual anatomical and functional central nervous system (CNS) organs (e.g. (hippocampi, frontal lobe, cerebellum, brain) for radiation damage by relating dose-volume histogram of the organs with information with neurocognitive test results.	2 years after radiotherapy
Sensitivity neurocognitive tests	Sensitivity of additional extensive neurocognitive tests	2 years after radiotherapy
Correlation advanced MRI and radiotherapy modality	Correlation of advanced MRI and treatment/dose parameters and radiotherapy modality (photon vs proton)	2 years after radiotherapy

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: Maastricht University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Danielle Eekers, Maastro Clinic, The Netherlands; Study Chair: Karen Zegers, Maastro Clinic, The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Anticipated): April 8, 2025
• Study Completion (Anticipated): April 8, 2025

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 2, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: MRI; Radiotherapy; Neurocognition; Meningioma
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neurocognitive Disorders; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Cognition Disorders; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Cognitive Dysfunction; Meningioma
• Other Study ID Numbers: PRECODE-MRI

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