Survival Outcomes and Symptom Benefit From Palliative Radiotherapy in Breast Cancer Patients With Leptomeningeal Disease

Abstract

The benefit of radiotherapy (RT) in poor-prognosis patients with leptomeningeal disease (LMD) is not well characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT.Patients with breast cancer and classic radiographic LMD (36% cytology-confirmed) treated with palliative whole brain and/or partial spine RT between 2000-2020 at a single academic institution were included in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method, and differences in subgroups were determined using the log-rank test. Multivariate Cox proportional hazards models adjusting for estrogen receptor (ER), progesterone receptor (PR), HER2, ECOG performance status (ECOG), and systemic disease status assessed factors associated with OS. Domain-specific and any symptom improvement were ascertained by chart review of patient- and physician-report, and a multivariate logistic regression model developed incorporating ER/PR status, HER2 status, ECOG and steroid use to identify factors associated with symptom benefit.Among 64 patients of median age 50 years (IQR 31-69), the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had concurrent brain metastases, and 57% of patients had ER+ and/or PR+ tumors, 22% HER2+, and 38% triple-negative disease. Among 92% of symptomatic patients whose primary symptom domains were cranial nerve deficit (34%), sensory/motor deficits due to intracranial disease (25%) sensory/motor deficits due to spine disease (27%), and headaches/nausea (14%), 42% had > 1 reported symptom domain. Two-thirds of patients were on steroids prior to RT, and only 13% of patients received intrathecal therapy. Following a median dose of 30 Gy in 10 fractions, symptom improvement in any domain was noted in 59% of patients with symptoms pre-RT, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in > 1 symptom domain. Overall survival was only 2.1 months (95% CI 1.8-3.3) in the triple-negative subgroup, and higher among patients with HER2+ disease (5.2 months, 95% CI 3.8-NR, P = 0.003). On multivariate analysis, ER+ (HR 0.4, 95% CI 0.2-0.8, P = 0.009) and HER2+ (HR 0.4, 95% CI 0.2-0.9, P = 0.018) disease were associated with improved OS. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2-11, P = 0.029).Even in this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yields symptomatic improvement, and may especially be of benefit among better-prognosis patients with hormone receptor-positive or HER2-positive disease.J. Takayesu: None. E. Sapir: Research Grant; LipoMedix, BioProtect. Consultant; AstraZeneca, MSD, Belong.Life. J. Xie: None. Y. Sun: None. A. Morikawa: Institutional research; Novartis, Lilly, Takeda, Eisai/H3b, Pfizer/National Comprehensive Cancer Network. L. Junck: Advisory Board; Orbus Therapeutics. D. Leung: None. Y. Umemura: None. J. Heth: None. W. Al-Holou: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. C. Mayo: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics.