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Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases

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Abstract

Purpose

Circulating tumor cells in cerebrospinal fluid are a quantitative diagnostic tool for leptomeningeal metastases from solid tumors, but their prognostic significance is unclear. Our objective was to evaluate CSF-CTC quantification in predicting outcomes in LM.

Methods

This is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quantification using the CellSearch® platform between 04/2016 and 06/2019. Information on neuroaxis imaging, CSF results, and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using multivariable Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identified through recursive partitioning analysis.

Results

Out of 290 patients with CNS metastases, we identified a cohort of 101 patients with newly diagnosed LM. In this group, CSF-CTC count (median 200 CTCs/3 ml) predicted survival continuously (HR = 1.005, 95% CI: 1.002–1.009, p = 0.0027), and the risk of mortality doubled (HR = 2.84, 95% CI: 1.45–5.56, p = 0.0023) at the optimal cutoff of ≥ 61 CSF-CTCs/3 ml. Neuroimaging findings of LM (assessed by 3 independent neuroradiologists) were associated with a higher CSF-CTC count (median CSF-CTCs range 1.5–4 for patients without radiographic LM vs 200 for patients with radiographic LM, p < 0.001), but did not predict survival.

Conclusion

Our data shows that CSF-CTCs quantification predicts survival in newly diagnosed LM, and outperforms neuroimaging. CSF-CTC analysis can be used as a prognostic tool in patients with LM and provides quantitative assessment of disease burden in the CNS compartment.

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Data availability

Anonymized data will be shared by request from any qualified investigator.

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Acknowledgements

Part of this study was presented at the Society of Neuro-Oncology Brain Metastases Conference in August 2020 and the Society of Neuro-Oncology Annual Meeting in November 2020.

Funding

This research was supported by grants from the Memorial Sloan Kettering Brain Tumor Center and the National Institutes of Health (P30-CA008748).

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Authors and Affiliations

  1. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Maria Diaz, Ivan S. Kotchetkov, Anna Skakodub & Elena Pentsova

  2. Hunter College, New York, NY, USA

    Priya Singh

  3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Alicia Meng, Christel Tamer & Robert J. Young

  4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Anne S. Reiner & Katherine S. Panageas

  5. Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lakshmi V. Ramanathan

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Contributions

Study design and data collection: MD, PS, IK, AS, AM, CT, RJY, EP. Statistical analysis and interpretation of the data: ASR, KSP, MD, PS, EP. Original draft preparation: MD, PS, EP. Critical revision of manuscript: MD, PS, IK, AS, ASR, KSP, LVR., AM, CT, RJY, EP.

Corresponding author

Correspondence to Elena Pentsova.

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Conflict of interest

Financial: RJY has received institutional grant funding from Agios, and consulting fees from Agios, Puma, NordicNeuroLab and ICON plc, all unrelated to this work. The remaining authors declare no conflict of interest. Non-financial: None.

Ethical approval

This retrospective study was approved by the Memorial Sloan Kettering Cancer Center (MSKCC) Institutional Review Board. Institutional waiver of informed consent was obtained due to minimal patient risk associated with participation in the study.

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Diaz, M., Singh, P., Kotchetkov, I.S. et al. Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases. J Neurooncol 157, 81–90 (2022). https://doi.org/10.1007/s11060-022-03949-1

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