2531 - Effect of Preoperative vs. Postoperative Radiation on Leptomeningeal Disease in Treatment of Brain Metastases

J. Hoyle¹, J. M. Markert², K. Riley², C. D. Willey¹, S. Marcrom¹, R. A. Popple³, J. B. Fiveash³, and M. Bredel¹; ¹University of Alabama at Birmingham Department of Radiation Oncology, Birmingham, AL, ²University of Alabama at Birmingham Department of Neurosurgery, Birmingham, AL, ³University of Alabama at Birmingham, Birmingham, AL

Purpose/Objective(s): Brain metastases are routinely treated with surgery, radiation, or a combination of these modalities. Leptomeningeal disease (LMD) is a form of metastatic disease that is associated with very poor prognosis for patients with metastasis from solid tumors and can develop as progression of untreated disease or from seeding after surgery. Surgery followed by stereotactic radiosurgery (SRS) has been shown to improve local control, but is associated with relatively high rates of LMD. Preoperative SRS is hypothesized to reduce rates of LMD by rendering tumor cells incapable of reproduction prior to potential surgical seeding. Materials/

Methods: This retrospective investigation of patients treated at a single institution compared rates of LMD in patients treated preoperatively with SRS to a previously published dataset of patients treated postoperatively. A total of 81 patients treated preoperatively between 2011 and 2023 were identified and received 12-15 Gy in a single fraction using linear accelerator (LINAC) radiosurgery. The postoperative cohort was treated between 2004 and 2015 and included 91 patients with some treated with Gamma Knife radiosurgery and others LINAC radiosurgery. This cohort primarily received single-fraction SRS, but several also received hypofractionated treatment. LMD was defined as diffuse or focal leptomeningeal enhancement and included enhancement within 5 mm of the index lesion. The Kaplan-Meier approach was used to plot survival curve estimates for months from surgery to LMD time-to-event outcomes.
Results: Of the 81 patients treated preoperatively with radiation, 6 (7.4%) developed LMD. From the postoperative cohort, 35 out of 91 (38%) patients developed LMD. Table 1 shows Kaplan-Meier estimates which demonstrate a significant difference in the time to LMD failure for patients receiving preoperative SRS, with an estimated mean time to LMD of 71 (95% COI, 63-79) months versus 44 (95% COI, 33-55) months (p<0.00002, log-rank test) for those treated postoperatively. The median estimated time to LMD was 17 mo (95% COI, 0-43) months for the postoperative SRS group but not reportable (not reached) for the preoperative SRS group.
Conclusion: Single-fraction preoperative radiosurgery with 12-15 Gy shows significant improvement in time to LMD failure compared to postoperative radiosurgery for patients being treated with combination therapy of radiation plus resection for brain metastases. Table 1: Kaplan-Meier Estimates of LMD

Treatment	Patients	LMD Events (%)	Mean Months to LMD (95% CI)	Standard Error of Mean	Median Months to LMD (95% CI)	Standard Error of Median
Postoperative	91	35 (38)	44 (33-55)	5.6	17 (0-43)	13
Preoperative	81	6 (7.4)	71 (63-78)	4.0	Not reached	Not reached
Overall	172	41 (24)	59 (51-67)	4.1	Not reached	Not reached