This early phase I trial identifies the side effects of stereotactic radiosurgery before surgery in treating patients with cancer that has spread to the brain (brain metastases). Radiation may stimulate an anti-tumor immune response. Giving stereotactic radiosurgery before surgery may reduce the risk of the cancer coming back after surgery.
PRIMARY OBJECTIVE: I. To determine the safety of pre-operative stereotactic radiosurgery (SRS) followed by surgery for brain metastasis. SECONDARY OBJECTIVES: I. To evaluate the immune niche in brain metastasis following SRS in the presence of low or high dose dexamethasone. II. To evaluate the impact of pre-operative SRS on survival outcomes. OUTLINE: Patients are assigned to 1 of 2 arms. ARM A: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone orally (PO) or intravenously (IV) for 2-21 days until the day of surgical resection. Patients then undergo surgical resection. ARM B: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive high dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection. After completion of study intervention, patients are followed up for 120 days, and then every 12 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Given PO or IV
Undergo surgical resection
Undergo SRS
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Incidence of adverse events grade 3 or greater
Evaluated using Common Terminology Criteria for Adverse Events. Tolerability of this regimen will be defined as \< 33% of patients develop grade \> 3 at 4 months. Adverse events will be summarized descriptively using frequencies and percentages.
Time frame: At 4 months post-treatment
Density of immune niche in brain metastases
Niche density will be assessed by immunofluorescence as described above. It will be summarized descriptively as the percent of tumor occupied by immune niche for each treatment arm, and will be compared between Arms A and B using a two-sample t-test or non-parametric equivalent, such as Mann-Whitney U test.
Time frame: Up to 2 years
Time to local recurrence (LR)
LR will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median LR will be estimated using the Brookmeyer-Crowley approach.
Time frame: From pre-operative stereotactic radiosurgery (SRS) to intracranial progression at the treated site, assessed up to 2 years
Time to anywhere brain failure (ABF)
ABF will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median TBF will be estimated using the Brookmeyer-Crowley approach.
Time frame: From preoperative SRS to intracranial progression at any site within the brain, assessed up to 2 years
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median OS will be estimated using the Brookmeyer-Crowley approach.
Time frame: From pre-operative SRS initiation to death, assessed up to 2 years
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