Longitudinal Prospective Study of Neurocognition & Neuroimaging in Primary BT Patients

Официальное название

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

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Longitudinal changes in imaging biomarker volume (cc) from volumetric MR imaging [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]
• Change in Memory after RT [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]
• Change in Executive Functioning after RT [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]
• Change in Attention/Processing Speed after RT [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]
• Change in Language functioning after RT [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]
• Change in Fine Motor Skills after RT [Срок оценки: 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 [Срок оценки: baseline (pre-treatment), 3 months, 6 months, 12 months post-treatment]

Критерии участия

Критерии включения

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

Критерии исключения

• Inability to undergo MRI with contrast
• Prior brain RT

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Moores Cancer Center — San Diego

Публикации

• 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. PMID 23095829
• 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.i PMID 33412257
• 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. PMID 33543265
• 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. PMID 32712255
• 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 PMID 31408667
• 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. PMID 28068234
• 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. PMID 22451194
• Connor M, Salans M, Karunamuni R, Unnikrishnan S, Huynh-Le MP, Tibbs M, Qian A, Reyes A, Stasenko A, McDonald C, Moiseenko V, El-Naqa I, Hattangadi-Gluth JA. Fine Motor Skill Decline After Brain Radiation Therapy-A Multivariate Normal Tissue Complication Probability Study of a Prospective Trial. Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):581-593. doi: 10.1016/j.ijrobp.2023.04.033. Epub 2023 M PMID 37150258

Идентификаторы

NCT: NCT05576103 · 131457

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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