Longitudinal Prospective Study of Neurocognition & Neuroimaging in Primary BT Patients

Longitudinal Prospective Study of Neurocognitive Outcomes and Multimodal Quantitative Neuroimaging Outcomes in Primary Brain Tumor Patients Receiving Brain Radiotherapy

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.

Study Overview

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

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 Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Lara J Rose; Phone Number: 858-822-6575; Email: ljrose@ucsd.edu
• Study Contact Backup: Name: Jona Hattangadi-Gluth, MD

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • Recruiting
      • Moores Cancer Center
      • Contact: Lara J Rose; Phone Number: 858-822-6575; Email: ljrose@ucsd.edu
      • Contact: Jona Hattangadi-Gluth, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Primary brain tumor patients

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Primary brain tumour patients receiving RT; Primary brain tumor patients are screened at time of consultation for this observational study, and the study population is diverse across sex/gender, and racial/ethnic groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal changes in imaging biomarker volume (cc) from volumetric MR imaging	To measure longitudinal changes in volume (cc) from volumetric MR imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Longitudinal changes in imaging biomarker mean diffusivity (MD) in white matter from DTI imaging	To measure longitudinal changes in MD (mm squared/second) from DTI imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Longitudinal changes in imaging biomarker fractional anisotropy (FA) in white matter from DTI imaging	To measure longitudinal changes in FA (unitless index between 0 and 1) from DTI imaging	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in Memory after RT	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.	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in Executive Functioning after RT	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	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in Attention/Processing Speed after RT	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.	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in Language functioning after RT	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.	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in Fine Motor Skills after RT	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	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Change in health-related quality of life (hrQoL) from baseline to 5 years after RT	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.	baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment

Collaborators and Investigators

• Sponsor: Jona Hattangadi-Gluth

Publications and helpful links

General Publications

• Greene-Schloesser D, Robbins ME. Radiation-induced cognitive impairment--from bench to bedside. Neuro Oncol. 2012 Sep;14 Suppl 4(Suppl 4):iv37-44. doi: 10.1093/neuonc/nos196.
• Huynh-Le MP, Tibbs MD, Karunamuni R, Salans M, Tringale KR, Yip A, Connor M, Simon AB, Vitzthum LK, Reyes A, Macari AC, Moiseenko V, McDonald CR, Hattangadi-Gluth JA. Microstructural Injury to Corpus Callosum and Intrahemispheric White Matter Tracts Correlate With Attention and Processing Speed Decline After Brain Radiation. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):337-347. doi: 10.1016/j.ijrobp.2020.12.046. Epub 2021 Jan 4.
• Salans M, Tibbs MD, Karunamuni R, Yip A, Huynh-Le MP, Macari AC, Reyes A, Tringale K, McDonald CR, Hattangadi-Gluth JA. Longitudinal change in fine motor skills after brain radiotherapy and in vivo imaging biomarkers associated with decline. Neuro Oncol. 2021 Aug 2;23(8):1393-1403. doi: 10.1093/neuonc/noab017.
• Tibbs MD, Huynh-Le MP, Karunamuni R, Reyes A, Macari AC, Tringale KR, Salans M, Yip A, Liu E, Simon A, McDonald CR, Hattangadi-Gluth JA. Microstructural Injury to Left-Sided Perisylvian White Matter Predicts Language Decline After Brain Radiation Therapy. Int J Radiat Oncol Biol Phys. 2020 Dec 1;108(5):1218-1228. doi: 10.1016/j.ijrobp.2020.07.032. Epub 2020 Jul 23.
• Tringale KR, Nguyen TT, Karunamuni R, Seibert T, Huynh-Le MP, Connor M, Moiseenko V, Gorman MK, Marshall A, Tibbs MD, Farid N, Simpson D, Sanghvi P, McDonald CR, Hattangadi-Gluth JA. Quantitative Imaging Biomarkers of Damage to Critical Memory Regions Are Associated With Post-Radiation Therapy Memory Performance in Brain Tumor Patients. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):773-783. doi: 10.1016/j.ijrobp.2019.08.003. Epub 2019 Aug 10.
• Seibert TM, Karunamuni R, Bartsch H, Kaifi S, Krishnan AP, Dalia Y, Burkeen J, Murzin V, Moiseenko V, Kuperman J, White NS, Brewer JB, Farid N, McDonald CR, Hattangadi-Gluth JA. Radiation Dose-Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging. Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):263-269. doi: 10.1016/j.ijrobp.2016.10.035. Epub 2016 Oct 31.
• Meyers CA, Rock EP, Fine HA. Refining endpoints in brain tumor clinical trials. J Neurooncol. 2012 Jun;108(2):227-30. doi: 10.1007/s11060-012-0813-8. Epub 2012 Mar 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: October 7, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neuroendocrine Tumors; Neoplasms, Vascular Tissue; Nerve Sheath Neoplasms; Meningeal Neoplasms; Neuroma; Brain Neoplasms; Meningioma; Neurilemmoma
• Other Study ID Numbers: 131457

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