2616 - Presentation and Outcomes for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Melanoma Presenting with Leptomeningeal Disease at the Time of Initial Central Nervous System Involvement

R. Tang¹, Y. Pina², H. H. M. Yu³, D. E. Oliver³, P. Forsyth⁴, M. N. Mills³, and K. A. Ahmed⁵; ¹University of South Florida Morsani College of Medicine, Tampa, FL, ²Moffitt Cancer Center, Tampa, FL, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ⁴H. Lee Moffitt Cancer Center and Research Institute, Department of Neuro-Oncology, Tampa, FL, ⁵Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Purpose/Objective(s): Though it is known that leptomeningeal disease (LMD) portends a poor prognosis, little is known of the presentation patterns and outcomes for patients who present with LMD at the time of initial central nervous system (CNS) involvement. Materials/

Methods: A cohort of 959 patients diagnosed with CNS metastasis (BM) between 2014 and 2019 with primary breast cancer, melanoma, and non-small cell lung cancer (NSCLC) was queried to identify patients diagnosed with LMD at the time of initial CNS metastasis. Time to event outcomes, including overall survival (OS) and craniospinal progression-free survival (CS-PFS), were calculated from the date of LMD diagnosis using the Kaplan-Meier method.
Results: There were 71 (7.4%) patients who were diagnosed with LMD at the time of initial CNS metastasis, which included 172, 488, and 299 breast cancer, NSCLC, and melanoma patients, respectively. Patients with breast cancer (19%) were significantly more likely to present with LMD compared to those with NSCLC (5%) and melanoma (6%, p<0.001). The diagnosis of LMD was confirmed by positive cerebrospinal fluid cytology in 24 cases (34%), while the remaining cases (66%) were diagnosed based upon MRI of the neuroaxis and clinical correlation. The median age at LMD diagnosis was 61 years (range: 34-86 years). Patients with NSCLC were older at diagnosis (p=0.001) and had a relatively shorter interval from initial cancer diagnosis (p<0.001). Most patients had intraparenchymal brain metastasis (76%) and extracranial systemic disease (73%) at the time of LMD diagnosis. Most patients received radiation therapy, including whole brain radiation therapy (90%), spinal radiation therapy (11%), or stereotactic radiosurgery (4%). Few patients received intrathecal therapy (N=22), which included thiotepa (N=8), methotrexate (N=6), and trastuzumab (N=3), amongst other agents. Few received immunotherapy (N=9), most commonly including pembrolizumab (N=6). Four patients received HER2-targeted therapy, 2 patients received EGFR-targeted therapy, and 2 patients received BRAF-targeted therapy. The median follow up was 1.6 months (range: 0.1-65 months). The 6-month OS and CS-PFS for the patients with LMD was 26% and 16%, respectively. There were no significant differences in outcomes by primary disease or the presence of concurrent brain metastases. Upon univariate analysis (UVA), only performance status, receipt of IT therapy, and receipt of HER2-targeted therapy predicted for improved OS. Upon univariate analysis (UVA), only performance status and receipt of HER2-targeted therapy predicted for improved CS-PFS.
Conclusion: The prognosis for patients who present with LMD at the time of initial CNS metastasis is poor overall. Breast cancer patients were the most likely to present with LMD at the time of their initial CNS metastases. Receipt of targeted therapy for patients with HER2+ breast cancer was associated with improved outcomes.