Incidence of Brain Metastasis as First Event in Patients with Esophageal Carcinoma: a Report from Three Prospective Alliance Clinical Trials

Purpose: Historically, reported incidence of brain metastasis secondary to esophageal carcinoma is low. We sought to determine the incidence of brain metastasis in a contemporary cohort of patients with carcinoma of the esophagus. Methods: Data from patients with localized esophageal carcinoma prospectively enrolled on three curative intent Alliance treatment trials (N0044, N0342, N044E) were reviewed including time to diagnosis of first progression event (brain versus other site) and overall survival. Results: Eighty-five patients comprised the cohort of which 85% were male and 86% had adenocarcinoma primary tumor histology. Thirty-nine of the 85 patients had documented progression to any site, and of those, brain metastasis occurred as the first event in 15% (6 of 39). Adenocarcinoma was the primary histology in all 6 patients and tumor grade was high (3 or 4) in 5 of the 6 patients (one not documented). Median time to brain metastasis (9.6 months) versus non-brain metastasis (12.4 months) and median survival after first progression (5.4 months versus 8.1 months, respectively) were not statistically different. Conclusion: In this prospective cohort of patients with esophageal carcinoma, those with high-grade adenocarcinoma appear to have a higher incidence of brain metastasis than historically reported. The pattern of brain metastases corroborates recent findings in terms of incidence, predominance of adenocarcinoma primary tumor histology, timing after diagnosis, and overall survival. Further study to confirm these findings, as well as the value of baseline, restaging and follow-up cranial imaging for brain metastasis is recommended. ClinicalTrials.gov Identifiers: NCT00022139 (NCCTG N0044), NCT00100945 (NCCTG N0342), and NCT00100945 (NCCTG N044E).