UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases

Cancer Clinical Trial

— IG-SRS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04343157
• Other study ID #: 170848
• Secondary ID: R01CA238783-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: University of California, San Diego
• Contact: Sheila Medina
• Phone: 858-822-6575
• Email: s4medina[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Brain Metastases, Adult
• Brain Neoplasms
• Cancer
• Neoplasm Metastasis
• Neurocognitive Function

Intervention

Radiation:
• 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.

Locations

Country	Name	City	State
United States	Moores Cancer Center	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
Jona Hattangadi-Gluth	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Verbal Memory from baseline to 3 months after SRS	To evaluate the change from baseline to 3-month post-SRS verbal memory performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. Verbal memory outcomes and measurements include: Hopkins Verbal Learning Test-Revised (HVLT-R)-Immediate, Delayed Recall. Scale of scores is 0-36 for Immediate, 0-12 for Delayed. For both tests, higher scores indicate better performance.	Change from Baseline (pre-treatment) to 3 months post treatment
Primary	Change in Executive Functioning from baseline to 3 months after SRS	To evaluate the change from baseline to 3-month post-SRS executive functioning performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. 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	Change from Baseline (pre-treatment) to 3 months post treatment
Primary	Change in Attention/Processing Speed from baseline to 3 months after SRS	To evaluate the change from baseline to 3-month post-SRS Attention/Processing Speed performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. 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	Change from Baseline (pre-treatment) to 3 months post treatment
Primary	Change in Language functioning from baseline to 3 months after SRS	To evaluate the change from baseline to 3-month post-SRS Language performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. 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.	Change from Baseline (pre-treatment) to 3 months post treatment
Secondary	Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging	To measure longitudinal changes in FA (unitless index between 0 and 1) from DTI imaging	baseline (pre-treatment), 3 months and 6 months post-treatment
Secondary	Longitudinal changes in imaging biomarker mean diffusivity (MD) from DTI imaging	To measure longitudinal changes in MD (mm squared/second) from DTI imaging	baseline (pre-treatment), 3 months and 6 months post-treatment
Secondary	Longitudinal changes in imaging biomarker volume from volumetric MR imaging	To measure longitudinal changes in volume (cc) from volumetric MR imaging	baseline (pre-treatment), 3 months and 6 months post-treatment

External Links

•   A Phase II Randomized Trial of Proton vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients with IDH Mutant, Low to Intermediate Grade Gliomas.
•   A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases.