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Investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement

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Abstract

Purpose

The mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20–30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement.

Methods

We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO.

Results

Among nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging.

Conclusion

In this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

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Acknowledgements

The authors would like to thank the UCLA Specialty Training and Advanced Research (STAR) program for support of this project. The authors would like to thank Dr. James N. Weiss for his support and Islam Abudayyeh for assistance with the anatomical figure.

Funding

This project was funded in part by NIH grant 5T32HL007895-19.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of California, Los Angeles, 200 UCLA Medical Plaza, Suite B265, Los Angeles, CA, 90095, USA

    R. Levin-Epstein & T. B. Kaprealian

  2. Department of Medicine/Interventional Cardiology, University of California, Los Angeles, Los Angeles, CA, USA

    P. Kumar, R. G. Fleming & J. M. Tobis

  3. David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA

    J. Rusheen

  4. Sidney Kimmel Medical College at the Thomas Jefferson University, Philadelphia, PA, USA

    Z. McWatters

  5. Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA

    W. Kim

  6. Department of Cardiology, University of California, San Diego, San Diego, CA, USA

    B. West

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Contributions

Drafting and revision of the manuscript was completed by RLE, PK, JR, RGF, ZM, WK, TBK, BW, and JMT. Data collection was performed by RLE, JR, ZM, PK, and RGF. TCD was performed by PK and RGF. Oversight of the study was performed by JMT, BW, TB, and WK.

Corresponding author

Correspondence to R. Levin-Epstein.

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Conflict of interest

Jonathan M Tobis: Speakers’ bureau for WL Gore. Rebecca Levin-Epstein, Preetham Kumar, Joshua Rusheen, Rubine Gevorgyan Fleming, Zoe McWatters, Won Kim, Tania B. Kaprealian, and Brian West declare no conflicts of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board at the University of California, Los Angeles (IRB #10-001634).

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Informed consent was obtained from all individual participants included in the study.

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Levin-Epstein, R., Kumar, P., Rusheen, J. et al. Investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement. Clin Transl Oncol 23, 783–787 (2021). https://doi.org/10.1007/s12094-020-02471-y

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  • DOI: https://doi.org/10.1007/s12094-020-02471-y

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