Evaluating Organotrophic Risk Factors, Time to Development, and Outcomes of Solitary Brain Metastasis After Esophagectomy: A Multicenter Cohort Study

Introduction: Brain metastases following esophagectomy for cancer are rare but can greatly affect quality of life. To date, risk factors for, time to development of, and treatment strategies for brain metastasis are not well defined. Methods: Consecutive patients treated with esophagectomy for clinical stage I–IVA esophageal cancer from 2010 to 2021 across five centers were included. Logistic regression analyses were performed to identify risk factors for development of solitary brain metastases. Overall survival was assessed using Kaplan–Meier analysis. Results: Of 3191 included patients, 91 (2.9%) developed solitary brain metastasis. Multivariable analysis identified increasing clinical nodal stage, adenocarcinoma (adjusted odds ratio [aOR] 4.00; 95% confidence interval [CI] 1.91–10), neoadjuvant chemoradiotherapy (aOR 2.18; 95% CI 1.19–4.28), and adjuvant therapy (OR 2.48; 95% CI 1.10–5.18) as risk factors for developing solitary brain metastases. Complete pathological responders were more likely to develop brain metastases than distant metastases (aOR 2.43; 95% CI 1.23–4.55). Patients with early solitary brain metastasis had the worst median overall survival (4.4 months, 95% CI 2.2–17) compared with classic (11 months, 95% CI 8.3–18) or late (7.4 months, 95% CI 2.1–not reached) (p = 0.20). Treatment involving surgery combined with radiation (adjusted hazard ratio [aHR] 0.10; 95% CI 0.05–0.20) resulted in better median overall survival (18 months, 95% CI 13–26) than did radiation (aHR 0.20; 95% CI 0.11–0.36) (10 months, 95% CI 6.1–14) or best supportive care (1.3 months, 95% CI 0.39–2.8) (p < 0.001). Conclusion: After esophagectomy for cancer, nodal involvement, adenocarcinoma, neoadjuvant and adjuvant therapy, and complete pathologic response appear to be risk factors for developing solitary brain metastases. Survival of selected patients with solitary brain metastasis is possible, especially if they are able to undergo surgery combined with radiation therapy.