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.

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.

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