Radiation Induced Alterations in Resting State Brain Networks in Pediatric Brain Tumor Patients

Study Overview
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Brief Summary
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With modern therapy, the survival rate for pediatric brain tumor patients has significantly improved, with over 70% of patients surviving their disease. However, this progress often comes at the cost of substantial morbidity, with cognitive deficits being the primary obstacle to independent living. Robust predictors of cognitive decline and a comprehensive understanding of the underlying mechanisms of cognitive injury remain elusive. This study will prospectively investigate alterations in brain resting state networks following radiation therapy using functional imaging. The hypothesis is that radiation therapy leads to dose-dependent alterations in functional connectivity in the networks associated with higher level cognition, ultimately leading to cognitive decline.

Official Title
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Assessing Radiation Induced Alterations in Resting State Brain Networks in Pediatric Brain Tumor Patients

Conditions
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Brain Tumor, Primary

Intervention / Treatment
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* Other: Cognitive testing
* Device: Resting State MRI/Precision functional mapping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 8 and 21 years of age, inclusive Newly diagnosed primary brain tumor of any location and any histology that will be treated with proton radiation therapy Life expectancy of at least one year Able to understand and willing to consent or assent to the research proposed, along with consent of legal guardian(s) if applicable Exclusion Criteria: Presence of visual impairment to an extent that the patient is unable to complete the computer testing Contraindication to MRI scan (i.e. due to cardiac pacemaker) Presence of programmable shunt or dental braces Requires sedation for MRI scans

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Brain tumor patients receiving proton radiation therapy<br>Patients between 8 and 21 years old (inclusive) with a newly diagnosed primary brain tumor that will be treated with proton radiation therapy | Other: Cognitive testing<br>* NIH Toolbox Cognitive Battery, the ADHD Rating Scale, the Neuro-QOL, the CLDQ, and the PROMIS Parent Proxy for Cognition at baseline (prior to completion of second week of radiation therapy) and again approximately 12 months after the completion of radiation therapy.<br>Device: Resting State MRI/Precision functional mapping<br>* During standard of care MRI at pre-treatment and approximately 12 months after the completion of radiation therapy.<br>* Other names: RSFC MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation induced effects on functional brain resting state connectivity | The investigators will compare resting state maps of each patient pre- and post-radiation therapy. The investigators will evaluate changes in the resting state architecture and compare to the average results that would be expected from a patient in the same age and sex. | Through 1 year follow-up | 
| Baseline characteristics of functional network architecture | The investigators will assess the unique architecture of brain networks at diagnosis and how significantly this architecture diverges from average healthy controls. | At baseline (day 1) | 
| Change in characteristics of functional network architecture | The investigators will assess brain system segregation which is measure of the connection and disconnection between different brain networks. These will be compared within individuals and compared to healthy controls. | Baseline and 1 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of radiation dose to changes in cognitive performance and resting state network connectivity | In an exploratory fashion, the investigators will evaluate the dose of radiation received to each resting state network to determine if functional connectivity changes in a dose dependent manner at 1 year. | At 1 year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton therapy, Radiation, Brain tumor