Clinical trial NCT04343157: UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases
Official title: UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Brain Metastases, Adult
Neurocognitive Function
Cancer
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2020-04-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Study patients will undergo MR imaging with DTI and 3D volumetric imaging at baseline (pre-SRS), and 1 month, 3 months, and 6 months afterwards. This regimen of post-SRS MR imaging is clinical standard of care. Segmentation of critical white matter and hippocampal volumes will be performed pre-SRS for use in brain SRS planning. Formal neurocognitive assessments will be performed at baseline and 3 months post-SRS.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients 18 years or older
2. One to three brain metastases targets, all smaller than 3 cm in diameter (intact or resected tumor bed)
3. 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)
4. Ability to answer questions and follow commands via neurocognitive testing
5. Estimated life expectancy greater than 6 months
6. Pathologic confirmation of extracerebral tumor site (eg, lung, breast, prostate) from either the primary site or a metastatic lesion
7. Willingness/Ability to undergo brain MRI scans
8. Able to give informed consent

Exclusion Criteria:

1. Pregnant or nursing women
2. Women of childbearing potential unwilling to use adequate contraception
3. Inability to complete a magnetic resonance imaging scan with contrast
4. 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)
5. Planned chemotherapy during SRS (on the day of SRS)
6. Previous whole brain radiation therapy
7. Leptomeningeal metastases (ineligible for SRS)
8. Metastases from primary germ cell tumor, small cell carcinoma, or primary CNS lymphoma (ineligible for SRS)

Primary outcomes:
measure: Change in Verbal Memory from baseline to 3 months after SRS
timeFrame: Change from Baseline (pre-treatment) to 3 months post treatment
measure: Change in Executive Functioning from baseline to 3 months after SRS
timeFrame: Change from Baseline (pre-treatment) to 3 months post treatment
measure: Change in Attention/Processing Speed from baseline to 3 months after SRS
timeFrame: Change from Baseline (pre-treatment) to 3 months post treatment
measure: Change in Language functioning from baseline to 3 months after SRS
timeFrame: Change from Baseline (pre-treatment) to 3 months post treatment
Secondary outcomes:
measure: Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging
timeFrame: baseline (pre-treatment), 3 months and 6 months post-treatment
measure: Longitudinal changes in imaging biomarker mean diffusivity (MD) from DTI imaging
timeFrame: baseline (pre-treatment), 3 months and 6 months post-treatment
measure: Longitudinal changes in imaging biomarker volume from volumetric MR imaging
timeFrame: baseline (pre-treatment), 3 months and 6 months post-treatment
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Moores Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Jona Hattangadi-Gluth, MD
role: PRINCIPAL_INVESTIGATOR
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