This is a single-arm, single-center pilot study in which 10 patients with one to four brain metastases diagnosed on brain magnetic resonance imaging (MRI) within the past 30 days will be evaluated for study eligibility and enrolled as appropriate.
INTERVENTION: Enrolled patients will receive stereotactic radiosurgery (SRS) to all metastases followed by surgical resection of resectable metastases within one to 10 days following SRS. Pathologic specimens will be analyzed, and the patient will enter a standard pattern of surveillance (brain MRI every three months for two years). STUDY RATIONALE: Given the increased risk of leptomeningeal failure with surgery followed by SRS as well as the risk of radiation necrosis, new paradigms in therapy delivery and sequencing are being explored. Areas of investigation include optimization of target volume, marginal expansion, multi-fractionation, timeliness of SRS after surgery, and delivery of SRS prior to surgical resection. In theory, advantages of preoperative SRS include better target delineation, sterilization of tumor cells prior to surgical disruption of the tumor, vascular supply, and cerebrospinal fluid (CSF) spaces, and resection of tissue that would otherwise be at risk of radiation necrosis. In 2014, Asher, et al. reported that the use of neoadjuvant SRS prior to surgery was both safe and effective (even for metastases \>3 cm) with no reported leptomeningeal recurrences or radiation necrosis. More recently, Patel et al. performed a retrospective comparison of preoperative versus postoperative SRS and reported no difference in local control, distant brain failure, or overall survival. Furthermore, the authors reported significantly lower rates of leptomeningeal carcinomatosis and radiation necrosis with preoperative SRS. Huff, et al. recently published a protocol for a phase II prospective trial designed to compare outcomes using preoperative SRS versus historically cited outcomes for postoperative SRS. This pilot study mirrors this design and aims to confirm study feasibility and to assess local control, central nervous system (CNS) progression-free survival, overall survival, rates of leptomeningeal spread, rates of radiation necrosis, and quality of life measures with the use of preoperative SRS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Maximum Tumor Diameter ≤ 2 cm = 20-24 Gy; Maximum Tumor Diameter 2.1-3.0 cm = 18 Gy; Maximum Tumor Diameter 3.1-5.0 cm = 15 Gy
Enrolled patients will receive GK-SRS to all metastases followed by surgical resection of resectable metastases within one to10 days following GK-SRS.
Following surgical resection, the patient will enter a standard pattern of surveillance (brain MRI every three months for two years).
Froedtert Hospital & Medical College of Wisconsin
Milwaukee, Wisconsin, United States
The Number of Subjects Undergoing Resection Following SRS.
All subjects undergoing resection following SRS will be documented.
Time frame: 10 days following SRS
The Number of Subjects With no Identifiable Disease Following Resection.
Identifiable disease will be determined by post-treatment MRI of the brain.
Time frame: 20 months
The Number of Subjects Achieving CNS Progression-free Survival.
Progression/progressive disease for this outcome measure was assessed at the index lesion using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Lesions must be contrast-enhancing on T1-weighted MRI, with at least one dimension ≥ 10 mm and visible on ≥ 2 axial slices. Progression is defined as a ≥ 20% increase in the sum of diameters (with a ≥ 5 mm absolute increase) or new lesions. Subjects will be evaluated at six, 12 and 18 months.
Time frame: 6, 12 and 18 months
The Number of Subjects Achieving Overall Survival.
The number of subjects alive at six, 12 and 18 months following surgical resection.
Time frame: 6, 12 and 18 months
The Number of Subjects With Leptomeningeal Carcinomatosis Using Preoperative SRS.
The number of subjects with this diagnosis will be documented.
Time frame: Two years
The Number of Subjects With Radiation Necrosis.
Radiation necrosis will be determined by radiographic appearance on posttreatment MRI. The number of patients with radiation necrosis will be documented.
Time frame: Two years
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The Number of Subjects Reporting a High Quality of Life.
Quality of life will be measured by the MD Anderson Symptom Inventory for brain tumor (MDASI-BT). The MDASI assesses the severity of symptoms at their worst in the last. 24 hours on a 0-10 numeric rating scale (NRS), with 0 being "not present" and 10 being "as bad as you can imagine." Health-related quality of life was assessed using the EQ-5D-5L instrument. While not identical to the MDASI, the EQ-5D-5L has been shown to correlate strongly with symptom burden and overall quality-of-life measures commonly used in oncology populations and was used here as a pragmatic surrogate for global quality-of-life assessment. A High Quality of Life was defined a priori as an EQ-5D-5L visual analog scale (VAS) score ≥80, reflecting a high level of self-reported overall health status. This threshold was selected to represent preserved or favorable quality of life and to allow for consistent longitudinal reporting across study time points.
Time frame: Every 3 months until two years; 3, 6, 9, 12, 15, and 18 months reported