2139 - Survival after Stereotactic Radiosurgery for Brain Metastases among Lung Cancer Patients Who Later Developed Leptomeningeal Disease
Presenter(s)
C. M. Liu1, A. Jambhale1, S. Koduri2, C. Oh3, N. Karaman4, K. Bernstein2, M. Mureb5, J. S. Silverman2, B. T. Cooper2, B. R. Donahue2, A. Gewirtz6, A. Miller7, J. R. McFaline-Figueroa7, D. Kondziolka8, and J. T. Yang9; 1NYU Grossman School of Medicine, New York, NY, 2Department of Radiation Oncology, NYU Langone Health, New York, NY, 3Biostatistics, Department of Population Health, NYU Langone Health, New York, NY, 4Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, NA, Turkey, 5Department of Neurosurgery, Westchester Medical Center, Vahalla, NY, 6Department of Neurology, NYU Grossman Long Island School of Medicine, New York, NY, 7Department of Neurology, NYU Grossman School of Medicine, New York, NY, 8Department of Neurosurgery, NYU Langone Health, New York, NY, 9Department of Radiation Oncology, NYU Grossman School of Medicine, New York, NY
Purpose/Objective(s):
Leptomeningeal disease (LMD) is a devastating cerebrospinal complication of advanced cancer. While stereotactic radiosurgery (SRS) is used to target brain metastases, little is known about factors that influence development of LMD after SRS for lung cancer.Materials/Methods:
A single-center retrospective cohort study identified 127 lung cancer patients who received SRS from 2008 to 2025 and later developed LMD. Central nervous system progression-free survival (CNS PFS), defined as radiographic or clinical evidence of new or worsened CNS disease, and overall survival (OS) starting from first SRS were estimated using the Kaplan-Meier method. Time to LMD was recorded from initial cancer diagnosis. Analysis was conducted with Cox proportional hazards model.Results:
122 (96%) patients had non-small cell lung cancer (NSCLC), 4 (3%) had small cell (SCLC), and 1 (1%) had a neuroendocrine carcinoid tumor. Median age was 64 years (IQR 57-71); 65% were female. 61% had driver mutations (EGFR 39%, KRAS 16%, ALK 6%). Median time from cancer diagnosis to LMD was 20 months (IQR 11-43). Median time from SRS to LMD was 8.5 months (IQR 3.4-20.4). Median OS was 45.3 months (95% CI 29.9–not reached) from SRS and 3.8 months (95% CI 2.8–7.2) from LMD. On univariate analysis, female sex (HR 0.66, 95% CI 0.45-0.95, p = 0.03) was associated with later LMD. Active extracranial disease (ECD) (HR 1.84, 95% CI 1.15-2.93, p = 0.01) and larger SRS target volume (1.030, 95% CI 1.01-1.06, p = 0.02) were associated with earlier LMD. The effects persisted in multivariate analysis for female sex (HR 0.51, 95% CI 0.34-0.77, p = 0.03) and active ECD (HR 2.54, 95% CI 1.52-4.25, p < 0.001). Median time to LMD for patients with active vs. stable ECD was 17 vs. 38 months, p = 0.01. Univariate analysis showed that active ECD was also associated with earlier progression (median CNS PFS was 22 vs. 39 months for active vs. stable ECD, HR 1.89, 95% CI 1.02-3.5, p = 0.04). On multivariate analysis, active ECD (HR 2.30, 95% CI 1.2-4.5, p = 0.02) and number of tumors treated with SRS (HR 1.04, 95% CI 1.002-1.1, p = 0.04) were associated with worse CNS PFS. Improved CNS PFS was independently associated with more SRS treatments (HR 0.86, 95% CI 0.73-0.999, p = 0.048) and targeted therapy exposure regardless of driver mutation status (HR 0.60, 95% CI 0.36-0.98, p = 0.04). On both univariate and multivariate analysis, active ECD was associated with worse OS after SRS ([HR 2.27, 95% CI 1.02-5.1, p = 0.04] and [HR 2.55, 95% CI 1.1-6.0, p = 0.03] respectively). Median OS for patients with active vs. stable ECD was 35 vs. 126 months, p = 0.04.Conclusion:
Among lung cancer patients treated with SRS for brain metastases who later developed LMD, active systemic disease was independently and significantly associated with shorter time to LMD from initial diagnosis, and shorter CNS PFS and OS after SRS. Our study highlights the need to monitor patients with active ECD more closely for CNS progression than patients with stable ECD.