MRI Biomarkers for Radiation-Induced Neurocognitive Decline Following SRS of Newly Diagnosed Brain Mets

Magnetic Resonance Imaging Biomarkers for Radiation-Induced Neurocognitive Decline Following Stereotactic Radiosurgery of Newly Diagnosed Brain Metastases: An Observational Pilot Study

Brain metastases are a source of much morbidity and mortality in adults with primary solid malignant tumors. With improvements in systemic therapy that prolong survival but have limited central nervous system penetration, patients with brain metastases are at increasing risk of developing and experiencing long-term side effects from treatment of brain metastases. The overarching goal of this study is to better understand the determinants of RT-associated changes in white and gray matter function and associated neurocognitive decline.

Study Overview

• Status: Recruiting
• Conditions: Neurocognitive Deficit; Brain Metastases; Radiation Exposure; White Matter Alterations

Detailed Description

The proposed study aims to provide novel and useful information for clinicians, both to help predict potential neurocognitive changes following SRS, and as a possible guide for SRS treatment alteration, whether through adjustment of dose or beam arrangements in relation to white matter tracts. In this observational pilot study of 20 patients, the association between RT-associated brain injury and neurocognitive function will be quantitatively assessed longitudinally over one year following SRS. The study team hypothesizes that, over this time, (1) there will be radiation dose-dependent reductions in regional white matter tract integrity and reduction in functional connectivity in the default mode network of gray matter, (2) there will be measurable decline in neurocognitive function, and (3) there will be an association between severity of radiation-induced brain injury on MRI and magnitude of neurocognitive functional decline. This association will relate, in part, to the location(s) affected.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Becky Green; Phone Number: 9849748440; Email: rlgreen@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill, Department of Radiation Oncology
      • Contact: Emily C Goldman; Phone Number: 984-974-8441; Email: emily_goldman@med.unc.edu
      • Principal Investigator: Colette J Shen, MD, PhD
      • Principal Investigator: Tong Zhu, PhD, DABR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed brain metastasis being treated with SRS.

Description

Inclusion Criteria:

• Histologic diagnosis of cancer
• Newly diagnosed brain metastasis being treated with SRS. Any extent of cranial disease permitted. Subsequent courses of SRS while on study permitted when clinically indicated.
• Patients are permitted to have undergone craniotomy and resection of metastasis/metastases if at least 1 other intact metastasis planned for definitive SRS is present. Receiving or previously received systemic therapy also permitted.
• Anticipated life expectancy at least 1 year
• Age ≥ 18 years
• Ability to read and comprehend written English and follow instructions in English
• Ability to provide informed consent

Exclusion Criteria:

• Previous radiation to the brain or head
• Previous malignancy - other than non-melanomatous skin cancer or cervical carcinoma in situ - and not disease-free for at least 3 years
• Previous severe head or brain injury
• History of a neurological disorder such as Epilepsy, Parkinson's, Alzheimer's, or Dementia
• Prisoners

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation-Induced White Matter Injury	Dose-dependent reductions in white matter integrity, as quantified by Diffusion Tensor MRI (DTI)-derived measures of change in diffusivity	One year after SRS completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Functional Connectivity	Dose-dependent alterations in functional connectivity, especially for the subsystems of the Default Mode Network (DMN), as measured by resting state functional MRI	One year after SRS completion
Neurocognitive Changes	Change in neurocognitive function, as measured by Delis-Kaplan testing, after SRS treatment	One year after SRS completion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between Changes in Functional Connectivity and Neurocognitive Changes	Correlation between magnitude of neurocognitive function decline and severity of radiation-induced brain injury	One year after SRS completion

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Colette J Shen, MD, PhD, University of North Carolina at Chapel Hill, Department of Radiation Oncology; Principal Investigator: Tong Zhu, PhD, DABR, University of North Carolina at Chapel Hill, Department of Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Leukoaraiosis
• Other Study ID Numbers: LCCC 1844

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No