Clinical trial NCT05576103: Longitudinal Prospective Study of Neurocognition & Neuroimaging in Primary BT Patients
Official title: Longitudinal Prospective Study of Neurocognitive Outcomes and Multimodal Quantitative Neuroimaging Outcomes in Primary Brain Tumor Patients Receiving Brain Radiotherapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Brain Tumor
Glioma
Meningioma
Schwannoma
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2022-10-12
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Primary brain tumor patients

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.

Eligibility criteria: 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

Primary outcomes:
measure: Longitudinal changes in imaging biomarker volume (cc) from volumetric MR imaging
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Longitudinal changes in imaging biomarker mean diffusivity (MD) in white matter from DTI imaging
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Longitudinal changes in imaging biomarker fractional anisotropy (FA) in white matter from DTI imaging
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in Memory after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in Executive Functioning after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in Attention/Processing Speed after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in Language functioning after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in Fine Motor Skills after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
measure: Change in health-related quality of life (hrQoL) from baseline to 5 years after RT
timeFrame: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Moores Cancer Center
state: California
Study officials:
References:
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.
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