Multi-institution, Non-randomized Trial of Neurocognitive Outcomes in Patients With Multiple, Newly-diagnosed Brain Metastases Managed Primarily With the Gamma Knife (GK) Radiosurgery System.
This will be a prospective, multi-institution, non-randomized trial of neurocognitive
outcomes in patients with multiple, newly-diagnosed brain metastases managed primarily with
stereotactic radiosurgery (SRS), specifically the Gamma Knife (GK) system. The goal of the
study is to enroll 45 patients with 1-10 newly-diagnosed brain metastases from varied
primary cancers with the largest intracranial tumor volume ≤10 cc, ≤15 cc total tumor
volume, absence of leptomeningeal disease on MRI, and Karnofsky performance status (KPS)
score ≥70 (unless due to intracranial disease), and KPS expected to improve to ≥70 with
treatment. The enrolled patients are expected to have fairly good pre-treatment cognitive
function, defined as online neurocognitive function (oNCF) assessment scores ≥70 (within 2
standard deviations of mean, 100).
All study participants will undergo standard, pre-treatment clinical evaluations that
include: complete clinical/neurologic exam, performance status assessment, systemic staging,
and diagnostic MRI of the brain. Upon enrollment, the patients will further undergo
high-resolution MRI, including track density imaging (TDI). The baseline neurocognitive
function (NCF) will be assessed by a short (20-30 minute) online test battery that can be
completed by patients at home, CogState assessment (22 minutes), as well as by a
comprehensive neuropsychological evaluation (2-3 hours). The eligible patients will
subsequently go on to receive a radiosurgical treatment for their brain metastases.
All patients will have treatment response assessments every 10-12 weeks consisting of a
clinical/neurologic exam, performance status evaluation, disease re-staging (if indicated),
and diagnostic MRI of the brain. If progressive disease is identified (radiographic
progression of treated lesions or new brain lesions), the patients will be considered for
"salvage" therapy which will include repeat SRS, whole-brain radiation therapy (WBRT),
surgery with or without brachytherapy or best supportive care (e.g. steroids only). The
preferred salvage therapy will be SRS provided that the re-treatment criteria are met. Along
with regular clinical MRIs, TDI will be obtained.
Mandatory comprehensive follow-up testing by a neuropsychologist (1-2 hours) will occur
every 10-12 weeks, starting 4 weeks after completion of SRS, and will continue at these
intervals even if salvage therapy is administered for intracranial recurrence. Online NCF
testing (oNCF and CogState) will take place in the office setting on the same day as a
comprehensive cognitive assessment. Patients will also have the option to do web-based oNCF
assessments from home but not more frequently than every 2 weeks. These optional assessments
will not be included in the data analysis. All study participants will be followed until
death or withdrawal from the study.
The primary aim of the study is to validate the oNCF battery and to demonstrate the
feasibility of its use in patients with metastatic brain disease. The former will be
accomplished by correlating the findings of the oNCF testing with those of a comprehensive
neurocognitive function (cNCF) assessment of a neuropsychologist. Every attempt will be made
to identify imaging correlates of neurocognitive function derived from high-resolution MRI,
and TDI. The aggregate data in combination with lesion location information (and the
corresponding treatment) should provide unique insights into mechanisms that underlie
radiation therapy (RT)-related brain injury. Because salvage therapy with WBRT is also
permitted and will likely be necessary in a subset of patients, some insights may also be
gained on the relative extent, specificity, and temporal evolution of post-treatment NCF
dysfunction of each treatment modality.
The data gained from this pilot study could form the basis of future trials of NCF outcomes
in cancer patients, especially if oNCF test battery is validated as this may provide a
cost-effective method for including NCF outcomes in clinical trials.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Gamma knife radiosurgery treatment
Two short oNCF assessments (Lumosity's Brain Power Test) will be performed at least 30 minutes prior to a clinical neurocognitive function (cNCF) assessments directed by a neuropsychologist at baseline and 6 months following Gamma knife treatment to assess changes in the participants' ability to complete all assessments.
baseline and 6-months following treatment
Igor J Barani, MD
University of California, San Francisco
United States: Institutional Review Board
|University of California, San Francisco||San Francisco, California 94143|