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

NCT05658731 | Recruiting DMC

• 2 other identifiers: J2255IRB00331759
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Brain Tumor; Head and Neck Cancer

Keywords

radiation therapy; pediatric

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Cumulative incidence of local and distant tumor recurrence

  up to 5 years after treatment

• Fractional anisotropy values

  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.

  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.

  baseline to 5 years

• characterize longitudinal CVLT scores in survivors of pediatric brain tumor who are ≥ 2 years post radiation

  baseline to 5 years

Study Arms (3)

Stratum A (new diagnosis, substructure informed radiation therapy)

EXPERIMENTAL

Patients will undergo radiation therapy which has been planned according to dose constraints to specific brain substructures.

Radiation: substructure informed planning; Other: Neurocognitive Testing; Diagnostic Test: MRI

Stratum B (patients ≥ 2 years after standard radiation therapy)

OTHER

Patients who completed radiation therapy under standard planning procedures ≥ 2 years ago.

Other: Neurocognitive Testing; Diagnostic Test: MRI

Stratum C (healthy controls matched to Stratum A)

OTHER

Healthy patients who are matched to Stratum A patients

Diagnostic Test: MRI

Interventions

substructure informed planning RADIATION

Radiation Therapy with substructure informed planning determined by the PI.

Stratum A (new diagnosis, substructure informed radiation therapy)

Neurocognitive Testing OTHER

California Verbal Learning Test (CVLT) and other cognition assessments.

Stratum A (new diagnosis, substructure informed radiation therapy); Stratum B (patients ≥ 2 years after standard radiation therapy)

MRI DIAGNOSTIC_TEST

Magnetic resonance imaging (MRI) using whole brain diffusion tensor imaging (DTI) and resting state functional MRI (rsfMRI).

Stratum A (new diagnosis, substructure informed radiation therapy); Stratum B (patients ≥ 2 years after standard radiation therapy); Stratum C (healthy controls matched to Stratum A)

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• United States Department of Defense: collaborator
• Clark Charitable Foundation: collaborator

Study Sites (2)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Sahaja Acharya, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sahaja Acharya, MD

CONTACT

202-537-4788; sachary7@jhmi.edu

Katie Lowe

CONTACT

410-955-8652; katielowe@jhmi.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: December 21, 2022
• Study Start: May 17, 2023
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2035
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)