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

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Abstract

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).

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Data Availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Brianna N. Tranby, M.A., medical writer in the Mayo Clinic Department of Radiation Oncology, for editorial contributions and assistance in preparation of this manuscript. We also thank Sherry Breaux, M.P.H., for her critical review of the manuscript. The data from NCCTG N0044, N0342, and N044E were obtained directly from the Alliance for Clinical Trials in Oncology, a National Clinical Trials Network cooperative group.

Funding

The research reported in this publication was supported by the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology) (https://acknowledgments.alliancefound.org). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA

    Ron S. Smith

  2. Department of Radiation Oncology, Mayo Clinic Health System, Mankato, MN, USA

    Ron S. Smith

  3. Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA

    Nathan R. Foster

  4. Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Aminah Jatoi

  5. Department of Medical Oncology, Mayo Clinic Health System, Mankato, MN, USA

    Stephan D. Thomé

  6. Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA

    Robert C. Miller

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Contributions

RSS and SDT designed the research, analyzed the results, and wrote the manuscript. NRF provided statistical analysis. RCM provided critical review and input. AJ was the study chair for NCCTG N0044, N0342, and N044E, and provided critical review of the manuscript. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Ron S. Smith.

Ethics declarations

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Exemption from IRB approval was granted by the Mayo Clinic IRB.

Consent to Participate

Informed consent was obtained from all individual participants on the original Alliance clinical trials, but further consent was not required for this data analysis.

Competing Interests

RCM receives funding from ASTRO for editorial services outside of the submitted work.

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Smith, R.S., Foster, N.R., Jatoi, A. et al. Incidence of Brain Metastasis as First Event in Patients with Esophageal Carcinoma: a Report from Three Prospective Alliance Clinical Trials. J Gastrointest Canc 54, 846–854 (2023). https://doi.org/10.1007/s12029-022-00871-7

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