2497 - Management of Multiple Brain Metastases with Serial Stereotactic Radiosurgery vs. Whole Brain Radiation Therapy

J. J. Chen¹, B. P. Ziemer¹, A. Witztum¹, K. L. Cui², L. Boreta¹, J. L. Nakamura¹, P. K. Sneed¹, O. Morin¹, D. P. I. Capaldi¹, and S. E. Braunstein¹; ¹Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, ²School of Medicine, University of California San Francisco, San Francisco, CA

Purpose/Objective(s): Some patients with multiple brain metastases (BM) may benefit from serial stereotactic radiosurgery (SRS), while forestalling neurocognitive effects associated with whole brain radiation therapy (WBRT). We hypothesized that overall survival (OS) and time to leptomeningeal disease (LMD) development would be similar among selected patients with =10 BM at first brain RT who are treated with serial SRS versus WBRT. Materials/

Methods: We retrospectively reviewed 101 patients with =10 BM treated at first SRS (12/2007-4/2023) and who received =2 Gamma Knife-based SRS treatments, either upfront or following WBRT. Patients with diffuse LMD at first brain RT were excluded. Demographic and clinical data were obtained from the electronic medical record or GammaPlan treatment planning and management software. Logistic regression analyses examined factors associated with SRS preceding WBRT. The Kaplan-Meier method determined OS, time from first SRS to WBRT, and time from first brain RT to LMD. The log-rank test compared differences in OS and time to LMD among patients who received upfront SRS versus WBRT. Cox regression analyses examined predictors of LMD development.
Results: 3,448 BM were treated over 308 SRS treatments, with a median of 27 lesions (IQR: 20-42) and 2 SRS treatments (IQR: 2-4) per patient. Median follow up was 19.3 months (IQR: 10.3-41.4). Most patients were female (63.3%) and had a primary histology of breast (36.6%) or lung (32.7%). At first SRS, median V12Gy was 14.7 cc (IQR: 8.0-24.1) and median overall mean prescription dose across lesions was 18.7 Gy (IQR: 18.1-19.0). On multivariable analysis, predictors of receiving upfront SRS included age = 60 (OR 4.66, 95% CI 1.41-17.80, p = 0.02) and cancer diagnosis within preceding 6 months (OR 9.73, 95% CI 1.54-194.16, p = 0.04). Median time from first SRS to WBRT was 9.2 months (IQR: 4.9-22.2). Overall, the 1- and 2-year probabilities of OS from first brain RT were 79.7% and 55.0%, while the 1- and 2-year probabilities of freedom from LMD were 70.3% and 35.1%, respectively. There were no differences in 1-year OS (76.7% vs 88.0%, p = 0.65) or 1-year freedom from LMD (67.9% vs 77.8%, p = 0.54) among patients who received upfront SRS versus WBRT, respectively. On multivariable analysis, intracranial progression within 6 months of first SRS (HR 2.92, 95% CI 1.18-7.26, p = 0.02) and number of brain metastases treated at first SRS (HR 1.15, 95% CI 1.08-1.22, p < 0.01) predicted for LMD. There was decreased risk of LMD with =2 lines of systemic therapy prior to SRS (HR 0.36, 95% CI 0.14-0.94, p = 0.04).
Conclusion: Selected patients have similar survival and LMD outcomes after receiving upfront SRS compared to WBRT. Intracranial progression within 6 months, number of brain metastases treated, and =3 lines of systemic therapy prior to first SRS were associated with increased risk of LMD. Further research is needed to ensure appropriate patient selection and adequate surveillance following serial SRS for multiple BM.