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Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis

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Abstract

Purpose

The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate molecular features of leptomeningeal metastasis (LM). Accordingly, we sought to systematically compare the diagnostic power or significance of ctDNA derived from cerebrospinal fluid (CSF) compared to plasma ctDNA in patients with LM.

Methods

A systematic review and meta-analysis was performed under the PRISMA guideline. We used PubMed, EMBASE, and the EuroPMC to search the literature using combinations of the following terms: circulating tumor DNA, ctDNA, circulating tumor cell, brain metastasis, leptomeningeal metastasis, outcome(s), and prognosis. We included all available English language studies that compared the diagnostic significance of CSF derived and serum ctDNA. All eligible studies level of bias was assessed using the New Castle Ottawa Scale (NOS).

Results

Our meta-analysis from 6 included studies (n = 226) that confirmed the diagnostic power of liquid biopsies in detecting genomic alteration is better when taking a CSF-derived samples than from the plasma (RR 1.46 [0.93; 2.29]; I2 = 92%; p-value < 0.01).

Conclusion

CSF ctDNA is better at describing molecular landscape for LM; such an understanding may ultimately help inform patient treatment and responses to therapy.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Universitas Pelita Harapan, Tangerang, Banten, Indonesia

    Jeremiah H. Wijaya & Julius July

  2. Mayo Clinic, Jacksonville, FL, USA

    Utsav D. Patel

  3. Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Miguel D. Quintero-Consuegra & Maria P. Aguilera-Peña

  4. Center for Research and Training in Neurosurgery, Department of Neurosurgery, Hospital Universitario de la Samaritana, Bogota, Colombia

    Humberto J. Madriñán-Navia

  5. Department of Neurosurgery, Barrow Neurological Institute, St Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Humberto J. Madriñán-Navia

  6. Department of Medicine, Universitas Trisakti, Jakarta, Indonesia

    Aulia W. Putra

  7. Department of Neurology, Louisiana State University Health Science Center at Shreveport, Los Angeles, CA, USA

    Saurabh Kataria

Authors
  1. Jeremiah H. Wijaya
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  2. Utsav D. Patel
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  3. Miguel D. Quintero-Consuegra
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  4. Maria P. Aguilera-Peña
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  5. Humberto J. Madriñán-Navia
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  6. Aulia W. Putra
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  7. Julius July
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  8. Saurabh Kataria
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed Jeremiah Hilkiah Wijaya, Utsav Dilipkumar Patel, Aulia Wiratama Putra, and Saurabh Kataria. The first draft of the manuscript was written by Jeremiah Hilkiah Wijaya and Julius July and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jeremiah H. Wijaya.

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Wijaya, J.H., Patel, U.D., Quintero-Consuegra, M.D. et al. Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis. J Neurooncol 165, 431–438 (2023). https://doi.org/10.1007/s11060-023-04519-9

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  • DOI: https://doi.org/10.1007/s11060-023-04519-9

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