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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease study. JAMA Oncol. 2017;3:524–48.

    Article  Google Scholar 

  2. 2.

    Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Besh S, Chao J, et al. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw. 2015;13:194–227.

    CAS  Article  Google Scholar 

  3. 3.

    Davis FG, Dolecek TA, McCarthy BJ, Villano JL. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data. Neuro Oncol. 2012;14:1171–7.

    Article  Google Scholar 

  4. 4.

    Cagney DN, Martin AM, Catalano PJ, Redig AJ, Lin NU, Lee EQ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol. 2017;19(11):1511–21.

    Article  Google Scholar 

  5. 5.

    Kothari N, Mellon E, Hoffe SE, Frakes J, Shridhar R, Pimiento J, et al. Outcomes in patients with brain metastasis from esophageal carcinoma. J Gastrointest Oncol. 2016;7:562–9.

    Article  Google Scholar 

  6. 6.

    Welch G, Ross HJ, Patel NP, Jaroszewski DE, Fleischer DE, Rule WG, et al. Incidence of brain metastasis from esophageal cancer. Dis Esophagus. 2017;30:1–6.

    CAS  Article  Google Scholar 

  7. 7.

    Wadhwa R, Taketa T, Correa AM, Sudo K, Campagna MC, Blum MA, et al. Incidence of brain metastases after trimodality therapy in patients with esophageal or gastroesophageal cancer: implications for screening and surveillance. Oncology. 2013;85:204–7.

    Article  Google Scholar 

  8. 8.

    Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.

    Google Scholar 

  9. 9.

    Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14:1286–312.

    Article  Google Scholar 

  10. 10.

    Weinberg JS, Suki D, Hanbali F, Cohen ZR, Lenzi R, Sawaya R. Metastasis of esophageal carcinoma to the brain. Cancer. 2003;98:1925–33.

    Article  Google Scholar 

  11. 11.

    Ogawa K, Toita T, Sueyama H, Fuwa N, Kakinohana Y, Kamata M, et al. Brain metastases from esophageal carcinoma: natural history, prognostic factors, and outcome. Cancer. 2002;94:759–64.

    Article  Google Scholar 

  12. 12.

    Song Z, Lin B, Shao L, Zhang Y. Brain metastases from esophageal cancer: clinical review of 26 cases. World Neurosurg. 2014;81:131–5.

    Article  Google Scholar 

  13. 13.

    Fidler IJ. The biology of brain metastasis: challenges for therapy. Cancer J. 2015;21:284–93.

    CAS  Article  Google Scholar 

  14. 14.

    Cancer Genome Atlas Research N, Analysis Working Group, Asan U, Agency BCC, Women's H Brigham I Broad, et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–75.

    Article  Google Scholar 

  15. 15.

    Limon D, Gal O, Gordon N, Katz L, Perl G, Purim O, et al. Brain metastasis in gastroesophageal adenocarcinoma and HER2 status. J Neurooncol. 2018;138:315–20.

    CAS  Article  Google Scholar 

  16. 16.

    Altaha R, Crowell E, Hobbs G, Higa G, Abraham J. Increased risk of brain metastases in patients with HER-2/neu-positive breast carcinoma. Cancer. 2005;103:442–3.

    Article  Google Scholar 

  17. 17.

    Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322:494–500.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank Marla Brunker, from the Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.

Funding

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.).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jaffer A. Ajani.

Ethics declarations

Conflict of interest

The authors have no potential conflicts of interest to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 32 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s10120-020-01075-3

Download citation

Keywords

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