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Background: Patients with brain metastases (BrMs) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with longer survival in patients with BrMs and, secondly, to compare the prognosis of patients with HER2 overexpression., Methods: We retrospectively reviewed patients with BrMs from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM., Results: The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. In this group, 71% of patients presented with stage III or IV disease, including 16% with synchronous primary metastatis and BrM. The median time to BrM was 10.1 months (interquartile range 1.7-22.8) and the median survival from BrM was 8.4 months (95% CI 4.8-16.8 months). On multivariable analysis, treatment with stereotactic radiosurgery (hazard ratio [HR] = 0.19; P = 0.04), surgical resection (HR 0.24; P = 0.03), and immunotherapy (HR 0.19; P = 0.04) were associated with increased survival while Karnofsky Performance Status (KPS) ≤70 (HR = 13.2; P < 0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ vs. 9.8 months HER2neg; P = 0.95)., Conclusions: The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics., (Copyright © 2024. Published by Elsevier Inc.)