Longitudinal Prospective Study of Neurocognition & Neuroimaging in Primary BT Patients

Recruiting

• Conditions: Primary Brain Tumor; Meningioma; Schwannoma; Glioma

• Registration Number: NCT05576103
• Lead Sponsor: Jona Hattangadi-Gluth

Brief Summary

In this proposal, the investigators introduce a novel, translational study to prospectively examine primary brain tumor patients undergoing fractionated radiation therapy to the brain. Quantitative neuroimaging, radiation dose information, and directed neurocognitive testing will be acquired through this study to improve understanding of cognitive changes associated with radiation dosage to non-targeted tissue, and will provide the basis for evidence-based cognitive- sparing brain radiotherapy.

Detailed Description

Background: Fractionated radiation therapy (RT) is a mainstay in the treatment of primary and metastatic brain tumors. However, RT to the brain is associated with an inevitable decline in neurocognitive function in up to 90% of patients who survive more than 6 months after irradiation. Radiation to the brain results in an inevitable decline in neurocognitive function, mediated by tissue injury to white matter, cortex and subcortical areas. With quantitative magnetic resonance imaging (MRI) techniques, investigators can directly and non-invasively measure such changes.

Objective/Hypothesis:

The purpose of this study is to examine radiation-induced imaging changes in normal brain tissue over time in primary brain tumor patients, and correlate these with neurocognitive outcomes. The overarching goal is to better identify sensitive brain regions so that future radiation techniques can be optimally designed to mitigate collateral damage.

Specific Aims:

1. To identify microstructural changes in subcortical white matter, hippocampus, and cortex associated with quantified regional exposure to fractionated brain radiotherapy using advanced quantitative neuroimaging imaging

2. To identify changes in neurocognitive functioning in primary brain tumor patients after brain radiotherapy

Study Design:

The investigators will prospectively enroll primary brain tumor patients undergoing fractionated partial brain radiation therapy. Patients will undergo volumetric and diffusion brain MRI (per clinical standard-of-care) and a neurocognitive battery of tests at baseline (pre-treatment), 3 months, 6 months, and 12 months post-treatment. Clinical data including age, gender, educational status, tumor size and histology, steroid use, antiepileptic drug use and chemotherapy will be recorded.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2022-10-07
• Study First Submitted QC: 2022-10-07
• Study First Posted: 2022-10-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-18
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Patients 18 years or older
2. Karnofsky performance status (KPS) ≥70
3. Life expectancy of ≥1 year
4. Primary brain tumor patients who will receive fractionated partial brain RT
5. Able to complete neurocognitive assessments

Exclusion Criteria

1. Inability to undergo MRI with contrast
2. Prior brain RT

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Longitudinal changes in imaging biomarker mean diffusivity (MD) in white matter from DTI imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To measure longitudinal changes in MD (mm squared/second) from DTI imaging
Change in Executive Functioning after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT executive functioning performance when performing fractionated partial brain RT. Executive functioning outcomes and measurements include: Controlled Oral Word Association Test (COWA): letter fluency, Trail Making Test Part B (TMT-B).; Scale of scores is: Controlled Oral Word Association Test (COWA): letter fluency: 0- no upper limit. Higher score indicates better performance Trail Making Test Part B (TMT-B): 0-240. Higher score indicates poorer performance
Longitudinal changes in imaging biomarker volume (cc) from volumetric MR imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To measure longitudinal changes in volume (cc) from volumetric MR imaging
Longitudinal changes in imaging biomarker fractional anisotropy (FA) in white matter from DTI imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To measure longitudinal changes in FA (unitless index between 0 and 1) from DTI imaging
Change in Memory after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT verbal memory performance when performing fractionated partial brain RT. Verbal memory outcomes and measurements include: Hopkins Verbal Learning Test-Revised (HVLT-R)-Immediate, Delayed Recall. Brief Visuospatial Memory Test-Revised (BVMT-R)- Total, Delayed Recall; Scale of scores is: Hopkins Verbal Learning Test-Revised (HVLT-R)-Immediate, Delayed Recall: 0-36 for Immediate, 0-12 for Delayed. For both tests, higher scores indicate better performance.; Brief Visuospatial Memory Test-Revised (BVMT-R)- Total, Delayed Recall: l: 0-36 for Immediate, 0-12 for Delayed.; For both tests, higher scores indicate better performance.
Change in Fine Motor Skills after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT Fine Motor Skills performance when performing fractionated partial brain RT in patients with primary brain tumor. Fine Motor Skills outcomes and measurements include: Trail Making Test Motor Speed; Grooved Pegboard Test
Change in Attention/Processing Speed after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT Attention/Processing Speed performance when performing fractionated partial brain RT. Attention/Processing Speed outcomes and measurements include: Trail Making Test Part A (TMT-A); Scale of scores is: Trail Making Test Part A (TMT-A): 0-240. Higher score indicates poorer performance.
Change in Language functioning after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT Language performance when performing fractionated partial brain RT in patients with primary brain tumor. Language outcomes and measurements include: Boston Naming Test (BNT), Controlled Oral Word Association Test (COWA): category fluency; Scale of scores is: Boston Naming Test (BNT): 0-60 Controlled Oral Word Association Test (COWA): category fluency: 0-no upper limit.; For both tests, higher score indicates better performance.
Change in health-related quality of life (hrQoL) from baseline to 5 years after RT	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment	To evaluate the change from baseline to post-RT health-related quality of life (hrQoL) when performing fractionated partial brain RT in patients with primary brain tumor. Quality of life outcomes and measurements include: Beck Depression inventory II (BDI II), Beck Anxiety Inventory (BAI) and FACT-BR (Functional Assessment of Cancer Therapy - Brain).; FACT-BR (Functional Assessment of Cancer Therapy - Brain) higher scores on each subscale indicate greater hrQoL.

Trial Locations

Locations (1)

Moores Cancer Center; 🇺🇸 San Diego, California, United States