Brain metastases in patients with upper gastrointestinal cancer is associated with proximally located adenocarcinoma and lymph node metastases



As cancer patients are surviving longer, more patients manifest brain metastases (BRMs). However, the rate of BRMs from upper gastrointestinal cancer is unclear. We therefore evaluated the frequency and prognostic effect of BRMs in this setting.


We analyzed records of 2348 patients who were treated between January 2002 and December 2016 for upper gastrointestinal cancer, including esophageal and gastroesophageal junction adenocarcinoma (EAC; proximal EAC, Siewert types I and II), esophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC; Siewert type III and stomach cancer) in our Gastrointestinal Medical Oncology Database. Frequency, risk factors, and survival after BRMs were evaluated.


Of 2348 patients, 68 (2.9%) had BRMs upon follow-up. The BRM rates were as follows: proximal EAC, 4.8%; Siewert type I, 5.9%; Siewert type II, 2.2%; Siewert type III, 0.7%; ESCC: 1.2%; and stomach cancer, 0%. Among EAC patients, Siewert type I and lymph node metastases were independent the risk factors for BRMs in the multivariable analysis. The median overall survival (OS) in the 68 patients with BRMs was only 1.16 years (95% CI 0.78–1.61). However, OS for patients who had a solitary BRM, who had BRM but no other distant metastasis, or who underwent surgery or stereotactic radiosurgery favorable.


Patients with proximally located adenocarcinoma, or with lymph node metastases are at a higher risk for BRMs and patients fare better after treatment of isolated BRM.

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We thank Marla Brunker, from the Edanz Group (, for editing a draft of this manuscript.


This research was supported by generous grants from the Caporella, Dallas, Sultan, Park, Smith, Frazier, Oaks, Vanstekelenberg, Planjery, and Cantu families, as well as from the Schecter Private Foundation, Rivercreek Foundation, Kevin Fund, Myer Fund, Dio Fund, Milrod Fund, and The University of Texas MD Anderson Cancer Center (Houston, Texas, USA) multidisciplinary grant program. This research was also supported in part by National Cancer Institute Grants CA129906, CA127672, CA138671, and CA172741; by Department of Defense Grants CA150334 and CA162445 (J.A.A.); and by a grant from the Japan Society for the Promotion of Science Overseas Research Fellowships and Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (K.H.).

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Correspondence to Jaffer A. Ajani.

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Harada, K., Hwang, H., Wang, X. et al. Brain metastases in patients with upper gastrointestinal cancer is associated with proximally located adenocarcinoma and lymph node metastases. Gastric Cancer 23, 904–912 (2020).

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  • Esophageal adenocarcinoma
  • Esophageal squamous-cell carcinoma
  • Gastroesophageal junction adenocarcinoma
  • Gastric adenocarcinoma
  • Brain metastases