The role of radiation therapy in leptomeningeal disease from breast cancer - a multicenter analysis.

Background: A subset of breast cancer patients will eventually develop leptomeningeal disease (LMD). There is a lack of large, in-depth analyses of the pattern of care and outcomes, with a particular focus on radiation therapy (RT). We report our experience in interdisciplinary LMD management, specifically addressing the role of RT. Materials and methods: This multicenter study analyzed female breast cancer patients with LMD treated at three academic centers between 2005 and 2020. Results: A total of 232 LMD patients were included. The median age at LMD diagnosis and Karnofsky performance status (KPS) were 54.5 years and 80%, respectively. Most patients presented with LMD localized in the brain (53.8%), underwent RT (66.4%), and received systemic therapy (61.6%). One hundred fifty-four patients received 205 RT courses, with whole-brain RT used most often (120 treatments, 58.5%). With a median follow-up of 4.5 months (range 0.1-72.0 months), 220 deaths were observed. The median overall survival (OS) was 4.7 months (95% confidence interval: 3.9-5.5). RT was not associated with improved OS and showed heterogeneous interactions across clinical contexts. Systemic therapy was associated with improved OS, especially in patients with a poor KPS. Discussion: This study highlights the dismal prognosis of LMD. RT was not associated with improved OS. Our findings, along with the reviewed literature, demonstrate that determining the potential benefit of RT on OS is challenging due to interactions between treatments and their timing, underscoring the need to clarify the optimal use and timing of RT in randomized clinical trials.