Cognitive Outcomes After Brain Substructure-informed Radiation Planning in Pediatric Patients

Study Overview
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Brief Summary
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The goal of this trial is to determine whether it is possible to minimize radiation dose to parts of the brain that are important for thinking and learning in children who require radiation to treat their tumor, and if this will help reduce neurocognitive (thinking and learning) impairments in these patients. Patients with newly diagnosed brain or head and neck tumors who are having radiation therapy will have neurocognitive testing and MRI imaging (both research and for regular care) done as part of their participation in the study. Survivors of childhood brain tumors who completed radiation therapy at least two years before joining the study, and have not had a recurrence, will have neurocognitive testing and research MRIs completed. Healthy children will also be enrolled and have research MRIs done. The researchers will use the radiation plan to determine how much radiation was delivered to different parts of the brain. The investigators will use the MRIs to determine how the normal brain is changing after treatment; and how this compares to patients who had standard radiation treatment or who never had a brain tumor. The neurocognitive testing will be compared among different groups to see how different treatment plans affect performance on neurocognitive tests.

Official Title
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Cognitive Outcomes After Brain Substructure-informed Radiation Planning in Pediatric Patients

Conditions
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Brain Tumor, Head and Neck Cancer

Intervention / Treatment
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* Radiation: substructure informed planning
* Other: Neurocognitive Testing
* Diagnostic Test: MRI


Participation Criteria
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Eligibility Criteria
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STRATUM A Eligibility Criteria aged 1 to <26 years of age tumor must be located in the brain or adjacent to the brain including but not limited to nasopharynx, paranasal sinuses and orbit treatment must include radiation therapy (either proton or photon) patients must not have completed radiation therapy Exclusion Criteria pregnancy patients who are not able to undergo neuro-cognitive testing, including children lacking English comprehension or children with premorbid neurological/neurodevelopmental disorders such as Down's syndrome or autism STRATUM B Eligibility Criteria diagnosed with a brain tumor at <26 years of age received radiation to the brain as part of therapy time from radiation start to study enrollment is ≥ 2 years there has not been disease recurrence from time of most recent radiation treatment to study enrollment Exclusion Criteria patients who are not able to undergo neuro-cognitive testing, including children lacking English comprehension or children with premorbid neurological/neurodevelopmental disorders such as Down's syndrome or autism STRATUM C Eligibility Criteria must be aged 5 to <26 years of age must be able to complete research imaging without sedation Exclusion Criteria must not have any major psychiatric, neurologic or medical diagnosis

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 26 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stratum A: patients with new diagnosis of brain or head and neck cancer who will be undergoing radiation therapy with substructure informed planning Stratum B: patients ≥ 2 years from radiation therapy for brain tumor who underwent standard planning radiation therapy Stratum C: healthy controls matched to Stratum A patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum A (new diagnosis, substructure informed radiation therapy)<br>Patients will undergo radiation therapy which has been planned according to dose constraints to specific brain substructures. | Radiation: substructure informed planning<br>* Radiation Therapy with substructure informed planning determined by the PI.<br>Other: Neurocognitive Testing<br>* California Verbal Learning Test (CVLT) and other cognition assessments.<br>Diagnostic Test: MRI<br>* Magnetic resonance imaging (MRI) using whole brain diffusion tensor imaging (DTI) and resting state functional MRI (rsfMRI).<br>|
| Other: Stratum B (patients ≥ 2 years after standard radiation therapy)<br>Patients who completed radiation therapy under standard planning procedures ≥ 2 years ago. | Other: Neurocognitive Testing<br>* California Verbal Learning Test (CVLT) and other cognition assessments.<br>Diagnostic Test: MRI<br>* Magnetic resonance imaging (MRI) using whole brain diffusion tensor imaging (DTI) and resting state functional MRI (rsfMRI).<br>|
| Other: Stratum C (healthy controls matched to Stratum A)<br>Healthy patients who are matched to Stratum A patients | Diagnostic Test: MRI<br>* Magnetic resonance imaging (MRI) using whole brain diffusion tensor imaging (DTI) and resting state functional MRI (rsfMRI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of plans that meet substructure-informed planning constraints | Number of plans that meet substructure-informed constraints (per protocol) divided by the total number of plans. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of local and distant tumor recurrence | Calculate the cumulative incidence of local and distant tumor recurrence. Local and tumor recurrence is determined by imaging and clinical symptoms. | up to 5 years after treatment | 
| Fractional anisotropy values | This outcome will measure changes in connection strength within brain networks. Fractional anisotropy values range from 0 to 1. Higher numbers are better. | baseline to two years | 
| compare the change in California Verbal Learning Test (CVLT) in patients whose radiation plans meet the dose constraints compared to those who do not for all patients in Stratum A. | Scores are age-standardized and with a mean of 100 and standard deviation of 15. Higher scores are better. | baseline to 3 years | 
| compare the change in NIH toolbox scores in patients whose radiation plans meet the dose constraints compared to those who do not for all patients in Stratum A. | Scores are age-standardized and with a mean of 100 and standard deviation of 15. Higher scores are better. | baseline to 5 years | 
| characterize longitudinal CVLT scores in survivors of pediatric brain tumor who are ≥ 2 years post radiation | Scores are age-standardized and with a mean of 100 and standard deviation of 15. Higher scores are better. | baseline to 5 years | 
| characterize longitudinal NIH toolbox scores in survivors of pediatric brain tumor who are ≥ 2 years post radiation | Scores are age-standardized and with a mean of 100 and standard deviation of 15. Higher scores are better. | baseline to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation therapy, pediatric