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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Brain Tumor
• Intervention / Treatment: Other: Neurocognitive Testing; Diagnostic test: MRI; Radiation: substructure informed planning

• Study Type: Interventional
• Enrollment (Estimated): 338
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sahaja Acharya, MD; Phone Number: 202-537-4788; Email: sachary7@jhmi.edu
• Study Contact Backup: Name: Katie Lowe; Phone Number: 410-955-8652; Email: katielowe@jhmi.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Recruiting
      • Sibley Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

1. STRATUM A

   1. 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

   2. 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

2. STRATUM B

   1. 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

   2. 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

3. STRATUM C

   1. Eligibility Criteria

      • must be aged 5 to <26 years of age
      • must be able to complete research imaging without sedation

   2. Exclusion Criteria

      • must not have any major psychiatric, neurologic or medical diagnosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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
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
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 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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: United States Department of Defense; Clark Charitable Foundation
• Investigators: Principal Investigator: Sahaja Acharya, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2023
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2035

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: pediatric; radiation therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms
• Other Study ID Numbers: J2255; IRB00331759 (Other Identifier: JHM IRB)

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