A Study of How Proton Beam Radiotherapy (PBRT) Affects Brain Function and Quality of Life in Children and Young Adults Undergoing Treatment for a Brain Tumor

Study Overview
=================
Brief Summary
-----------------
The researchers are doing this study to find out if there are differences in the resting state brain networks of children and young adults (ages 6-25) after treatment with proton beam radiation therapy (PBRT). The researchers will use resting state functional connectivity magnetic resonance imagining (rs-fcMRI) scanning to detect these differences. The researchers will also check for differences in participants' thinking and quality of life through a cognitive assessment and a questionnaire. Both people undergoing PBRT for a brain tumor and healthy people will take part in this study so that the researchers can compare the brain networks (connections in the brain that are involved in certain function, such as memory or attention), thinking patterns, and quality of life of these two groups of participants. The study researchers think that rs-fcMRI scans may be an effective way to look at the brain networks after treatment with PBRT and see if this treatment causes differences in those networks, including damage to the brain (neurotoxicity). rs-fcMRI scans take images when a patient is in a resting state, which means the patient is not performing a task or thinking about anything in particular. This study will provide valuable information about how PBRT affects brain networks, thinking (cognitive) abilities, and quality of life in children and young adults. The study results may have an impact on future treatment approaches for brain cancer and the use of PBRT in children and young adults.

Official Title
-----------------
Neuroimaging Biomarkers of Impaired Neurocognitive Functioning After Cranial Proton Beam Radiotherapy For Treatment of Brain Tumors In Pediatric Patients

Conditions
-----------------
Brain Tumor, Metastatic Brain Tumor

Intervention / Treatment
-----------------
* Diagnostic Test: Resting-state functional connectivity MRI
* Other: Neurocognitive battery with quality-of-life assessment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients Treated for Brain Tumors: The patient has been diagnosed with a primary or metastatic brain tumor The patient has been recommended to receive cranial PBRT for a primary or metastatic brain tumor The patient is between the ages of 6 through 25 at time of consent As per medical record or patient report (based on prior tolerance of MRI), the participant is able to tolerate MRI without sedation (i.e., general anesthesia). Patients will take medications as prescribed or directed by the patient's physician. If in accordance with their prescribed regimen, agents that may impact the CNS, such as benzodiazepines and/or antihistamines, should be avoided on the day of imaging and neurocognitive assessment. Healthy Control Participants: The control has no major medical illness, as determined by medical interview by study physician As per parent report, the control is between the ages of 6 through 25 at time of consent As per parent report, the control is able to tolerate an MRI without sedation (i.e., general anesthesia). Participants should only take medications as prescribed or directed by their physician. They should not take additional medications, such as antihistamines, for the purpose of tolerating MR imaging. Exclusion Criteria: As per self or parent report, the participant has completed any portion of the neuropsychological battery used in this study within the last year. As per medical record or self or parent report, there is an existing diagnosis of intellectual disability and/or prior IQ testing that documents Full Scale IQ standard score <70 at baseline. As per medical record, there is an existing diagnosis of psychiatric disorder or untreated mood disturbance, prior stroke or intracranial hemorrhage, or neurodegenerative disease. The participant has an MRI contraindication (e.g., implanted ferromagnetic devices, claustrophobia) as per radiology clinical operating procedures. As per self or parent report, non-fluency in English language as demonstrated by current educational placement in a non-English-speaking classroom setting.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This prospective, cross-sectional, pilot clinical trial will incorporate rs-fcMRI and a full post- PBRT cognitive battery including quality of life assessment for pediatric patients using a multidisciplinary team.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients<br>A full neurocognitive battery with quality-of-life assessment will be conducted and an rs-fcMRI sequence will be added to the brain MRI performed as standard of care follow-up between 3-5 months post-PBRT. | Diagnostic Test: Resting-state functional connectivity MRI<br>* participants will undergo functional MRI<br>Other: Neurocognitive battery with quality-of-life assessment<br>* Cognitive and quality of life assessments performed by a trained neuropsychologist<br>|
| Experimental: healthy matched controls<br>Healthy participants will be asked to complete the MRI scan and undergo neurocognitive assessment. | Diagnostic Test: Resting-state functional connectivity MRI<br>* participants will undergo functional MRI<br>Other: Neurocognitive battery with quality-of-life assessment<br>* Cognitive and quality of life assessments performed by a trained neuropsychologist<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in the resting state brain networks of children and young adults | A single rs-fcMRI sequence will be added to the MRI performed as standard of care follow-up 3-5 months after completion of cranial PBRT in pediatric patients treated for brain tumors to assess for early post-PBRT network disruption. Using resting state functional connectivity magnetic resonance imagining (rs-fcMRI) scanning to detect these differences. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Proton Beam Radiotherapy (PBRT), Cognitive battery assessment, Quality of life assessment