UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases

Официальное название

UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions

Обзор

In this proposal, the investigators introduce advanced diffusion and volumetric imaging techniques along with innovative, automated image parcellation methods to identify critical brain regions, incorporate into cognitive-sparing SRS, and analyze biomarkers of radiation response. This work will advance the investigators' understanding of neurocognitive changes after brain SRS and help create interventions that preserve cognitive-function in brain metastases patients.

Подробное описание

Background: Brain metastases affect one third of adult cancer patients. Stereotactic radiosurgery (SRS) is standard of care for patients with limited brain metastases. Yet most patients will experience post-treatment cognitive decline given the potential for high doses to eloquent white matter and the hippocampus.

Objective/Hypothesis: The investigator's team has developed innovative, robust imaging methods and automated segmentation techniques to identify critical white-matter tracts and the hippocampus using advanced diffusion tensor imaging (DTI) and volumetric imaging. These novel imaging techniques also allow us to directly and non-invasively measure microstructural changes after RT to critical brain structures in vivo. The investigators will use these advanced imaging technologies in a prospective trial of cognitive-sparing brain SRS for brain metastases patients.

Specific Aims: 1: To evaluate whether relative sparing of eloquent white matter tracts (critical for memory, language, attention, and executive functioning) and hippocampi from high doses during brain SRS results in improved 3-month post-SRS cognitive performance relative to historical controls in patients with 1 to 3 brain metastases. 2: To measure longitudinal trends in white matter damage (using DTI) and hippocampal atrophy (using volumetric change) among patients receiving cognitive-sparing brain SRS and correlate these imaging biomarkers with domain-specific cognitive outcomes.

Study Design: The investigators will prospectively enroll 60 adult patients with 1-3 brain metastases who are eligible for brain SRS and MRI. Patients will undergo MRI with DTI and 3D volumetric imaging at baseline (pre-SRS) and 1 month, 3 months, and 6 months afterwards. White matter and hippocampal segmentation will be performed and critical regions integrated into cognitive-sparing brain SRS planning with automated knowledge-based optimization. Cognitive-sparing dose constraints are derived from previous data. A well-established, validated battery of neurocognitive tests will be performed at baseline and 3 months post-SRS. Cognitive deterioration rate will be compared between the current trial and historical controls and linear regression used to analyze patient, tumor, and treatment related predictors of cognitive decline. Statistical modeling will be used to analyze changes in imaging biomarkers as a function of time and radiation dose, and these changes will be tested for association with domain-specific cognitive tests. Spatial sensitivity to RT dose across white matter tracts will be analyzed.

Вмешательства

• Лучевая терапия Cognitive Sparing Brain Stereotactic Radiosurgery (SRS)
  In this proposal, the investigators introduce advanced diffusion and volumetric imaging techniques along with innovative, automated image parcellation methods to identify critical brain regions, incorporate into cognitive-sparing SRS, and analyze biomarkers of radiation response. This work will advance the investigators' understanding of neurocognitive changes after brain SRS and help create interventions that preserve cognitive-function in brain metastases patients.

Первичные конечные точки

• Change in Verbal Memory from baseline to 3 months after SRS [Срок оценки: Change from Baseline (pre-treatment) to 3 months post treatment]
• Change in Executive Functioning from baseline to 3 months after SRS [Срок оценки: Change from Baseline (pre-treatment) to 3 months post treatment]
• Change in Attention/Processing Speed from baseline to 3 months after SRS [Срок оценки: Change from Baseline (pre-treatment) to 3 months post treatment]
• Change in Language functioning from baseline to 3 months after SRS [Срок оценки: Change from Baseline (pre-treatment) to 3 months post treatment]

Вторичные конечные точки (3)

• Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging [Срок оценки: baseline (pre-treatment), 3 months and 6 months post-treatment]
• Longitudinal changes in imaging biomarker mean diffusivity (MD) from DTI imaging [Срок оценки: baseline (pre-treatment), 3 months and 6 months post-treatment]
• Longitudinal changes in imaging biomarker volume from volumetric MR imaging [Срок оценки: baseline (pre-treatment), 3 months and 6 months post-treatment]

Критерии участия

Критерии включения

• Patients 18 years or older
• One to three brain metastases targets, all smaller than 3 cm in diameter (intact or resected tumor bed)
• Eastern cooperative Oncology Group (ECOG) performance status 0-2 (score of 0, no symptoms; 1, mild symptoms; 2, symptomatic, <50% in bed during the day)
• Ability to answer questions and follow commands via neurocognitive testing
• Estimated life expectancy greater than 6 months
• Pathologic confirmation of extracerebral tumor site (eg, lung, breast, prostate) from either the primary site or a metastatic lesion
• Willingness/Ability to undergo brain MRI scans
• Able to give informed consent

Критерии исключения

• Pregnant or nursing women
• Women of childbearing potential unwilling to use adequate contraception
• Inability to complete a magnetic resonance imaging scan with contrast
• Tumor directly invading the critical area to be spared (for example a patient with tumor invading a critical white matter tract; ineligible for cognitive-sparing)
• Planned chemotherapy during SRS (on the day of SRS)
• Previous whole brain radiation therapy
• Leptomeningeal metastases (ineligible for SRS)
• Metastases from primary germ cell tumor, small cell carcinoma, or primary CNS lymphoma (ineligible for SRS)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Moores Cancer Center — San Diego

Публикации

• Arvold ND, Lee EQ, Mehta MP, Margolin K, Alexander BM, Lin NU, Anders CK, Soffietti R, Camidge DR, Vogelbaum MA, Dunn IF, Wen PY. Updates in the management of brain metastases. Neuro Oncol. 2016 Aug;18(8):1043-65. doi: 10.1093/neuonc/now127. PMID 27382120
• Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Butowski N, Fenstermaker RA, Forsyth P, Hattangadi-Gluth J, Holdhoff M, Howard S, Junck L, Kaley T, Kumthekar P, Loeffler JS, Moots PL, Mrugala MM, Nagpal S, Pandey M, Parney I, Peters K, Puduvalli VK, Ragsdale J, Rockhill J, Rogers L, Rusthoven C, Shonka N, Shrieve DC, Sills AK, Swinnen LJ, Tsien C, Weiss S, Wen PY, Willmarth N, Bergman MA, En PMID 29118226
• Scoccianti S, Detti B, Cipressi S, Iannalfi A, Franzese C, Biti G. Changes in neurocognitive functioning and quality of life in adult patients with brain tumors treated with radiotherapy. J Neurooncol. 2012 Jun;108(2):291-308. doi: 10.1007/s11060-012-0821-8. Epub 2012 Feb 18. PMID 22354791
• 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
• Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi PMID 27458945
• Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2. PMID 19801201
• Lin NU, Wefel JS, Lee EQ, Schiff D, van den Bent MJ, Soffietti R, Suh JH, Vogelbaum MA, Mehta MP, Dancey J, Linskey ME, Camidge DR, Aoyama H, Brown PD, Chang SM, Kalkanis SN, Barani IJ, Baumert BG, Gaspar LE, Hodi FS, Macdonald DR, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurologica PMID 23993385
• Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomis PMID 28687377

Идентификаторы

NCT: NCT04343157 · 170848 · R01CA238783-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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