Skip to main content

Advertisement

SpringerLink
Log in

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors

  • Case Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors.

Methods

We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival.

Results

Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7–639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89–481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively.

Conclusions

CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The source data is available upon reasonable request to the corresponding author.

References

  1. Barbour AB, Kotecha R, Lazarev S, Palmer JD, Robinson T, Yerramilli D, Yang JT (2023) Radiation Therapy in the management of Leptomeningeal Disease from solid tumors. Adv Radiat Oncol. https://doi.org/10.1016/j.adro.2023.101377

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yang JT, Wijetunga NA, Pentsova E, Wolden S, Young RJ, Correa D, Zhang Z, Zheng J, Steckler A, Bucwinska W et al (2022) Randomized phase II trial of Proton Craniospinal Irradiation Versus Photon involved-field radiotherapy for patients with solid Tumor Leptomeningeal Metastasis. J Clin Oncol JCO2201148. https://doi.org/10.1200/JCO.22.01148

  3. Nora Dickson M, Tsinberg P, Tang Z, Bischoff FZ, Wilson T, Leonard EF (2011) Efficient capture of circulating tumor cells with a novel immunocytochemical microfluidic device. Biomicrofluidics 5:34119–3411915. https://doi.org/10.1063/1.3623748

    Article  CAS  PubMed  Google Scholar 

  4. Nayak L, Fleisher M, Gonzalez-Espinoza R, Lin O, Panageas K, Reiner A, Liu CM, Deangelis LM, Omuro A (2013) Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Neurology 80:1598–1605 discussion 1603. https://doi.org/10.1212/WNL.0b013e31828f183f

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wooster M, McGuinness JE, Fenn KM, Singh VM, Franks LE, Lee S, Cieremans D, Lassman AB, Hershman DL, Crew KD et al (2022) Diagnosis of Leptomeningeal Metastasis in Women with breast Cancer through identification of Tumor cells in Cerebrospinal Fluid using the CNSide Assay. Clin Breast Cancer 22:e457–e462. https://doi.org/10.1016/j.clbc.2021.11.002

    Article  CAS  PubMed  Google Scholar 

  6. Appel H, Odia Y, Saxena A, Roy M, Mohler A, Kotecha R, Hall MD, Ahluwalia MS, Mehta MP, Castaneda SA (2023) Evaluating the diagnostic performance of leptomeningeal diagnosis with CNSide compared to standard cytology. J Clin Oncol 41

  7. van Bussel MTJ, Pluim D, Milojkovic Kerklaan B, Bol M, Sikorska K, Linders DTC, van den Broek D, Beijnen JH, Schellens JHM, Brandsma D (2020) Circulating epithelial tumor cell analysis in CSF in patients with leptomeningeal metastases. Neurology 94:e521–e528. https://doi.org/10.1212/WNL.0000000000008751

    Article  CAS  PubMed  Google Scholar 

  8. Diaz M, Singh P, Kotchetkov IS, Skakodub A, Meng A, Tamer C, Young RJ, Reiner AS, Panageas KS, Ramanathan LV et al (2022) Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases. J Neurooncol 157:81–90. https://doi.org/10.1007/s11060-022-03949-1

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ghaferi AA, Schwartz TA, Pawlik TM (2021) STROBE reporting guidelines for Observational studies. JAMA Surg 156:577–578. https://doi.org/10.1001/jamasurg.2021.0528

    Article  PubMed  Google Scholar 

  10. Le Rhun E, Weller M, Brandsma D, Van den Bent M, de Azambuja E, Henriksson R, Boulanger T, Peters S, Watts C, Wick W et al (2017) EANO-ESMO clinical practice guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol 28:iv84–iv99. https://doi.org/10.1093/annonc/mdx221

    Article  PubMed  Google Scholar 

  11. NCCN (2023) National Comprehensive Cancer Network: Central Nervous System Cancers (Version 1.2023)

  12. Hyun JW, Jeong IH, Joung A, Cho HJ, Kim SH, Kim HJ (2016) Leptomeningeal metastasis: clinical experience of 519 cases. Eur J Cancer 56:107–114. https://doi.org/10.1016/j.ejca.2015.12.021

    Article  PubMed  Google Scholar 

  13. Wijetunga NA, Boire A, Young RJ, Yamada Y, Wolden S, Yu H, Kris M, Seidman A, Betof-Warner A, Diaz M et al (2021) Quantitative cerebrospinal fluid circulating tumor cells are a potential biomarker of response for proton craniospinal irradiation for leptomeningeal metastasis. Neurooncol Adv 3:vdab181. https://doi.org/10.1093/noajnl/vdab181

    Article  PubMed  PubMed Central  Google Scholar 

  14. Malani R, Bhatia A, Warner AB, Yang JT (2023) Leptomeningeal Carcinomatosis from Solid Tumor malignancies: treatment strategies and biomarkers. Semin Neurol 43:859–866. https://doi.org/10.1055/s-0043-1776996

    Article  PubMed  Google Scholar 

  15. Ogluszka M, Orzechowska M, Jedroszka D, Witas P, Bednarek AK (2019) Evaluate cutpoints: adaptable continuous data distribution system for determining survival in Kaplan-Meier estimator. Comput Methods Programs Biomed 177:133–139. https://doi.org/10.1016/j.cmpb.2019.05.023

    Article  PubMed  Google Scholar 

  16. Cantor AB, Shuster JJ (1994) Re - dangers of using Optimal cutpoints in the evaluation of prognostic factors. Jnci-J Natl Cancer I 86:1798–1799. https://doi.org/10.1093/jnci/86.23.1798-a

    Article  CAS  Google Scholar 

  17. Heagerty PJ, Lumley T, Pepe MS (2000) Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56:337–344. https://doi.org/10.1111/j.0006-341x.2000.00337.x

    Article  CAS  PubMed  Google Scholar 

  18. Chabot K, Osei-Gyening I, Estrera R, Yang J, Pentsova E, Boire A, Wilcox J (2023) EPID-04. EVOLVING SURVIVAL IN PATIENTS WITH LEPTOMENINGEAL METASTASES FROM SOLID TUMORS. Neuro Oncol 25:v115

    Article  Google Scholar 

Download references

Acknowledgements

We thank the University of Washington biostatistics consulting service for their input on statistical analysis, specifically thanking Taek Son, Ethan Ashby, James Peng, and Patrick Heagerty.

Funding

Not applicable.

Author information

Author notes

  1. Vyshak Venur and Jonathan T. Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, University of Washington– Fred Hutchinson Cancer Center, Seattle, WA, USA

    Andrew B. Barbour, Molly Blau, Lia M. Halasz, Simon S. Lo, Yolanda D. Tseng & Jonathan T. Yang

  2. Formerly Employed at Biocept, San Diego, CA, USA

    Barbara Blouw

  3. Department of Neurology, University of Washington– Alvord Brain Tumor Center, Seattle, WA, USA

    Lynne P. Taylor, Jerome J. Graber & Vyshak Venur

  4. Division of Hematology-Oncology, Scripps Cancer Center, La Jolla, CA, USA

    Tresa McGranahan

  5. Division of Medical Oncology, University of Washington– Fred Hutchinson Cancer Center, Seattle, WA, USA

    Vyshak Venur

Authors
  1. Andrew B. Barbour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Blouw
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynne P. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jerome J. Graber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tresa McGranahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Molly Blau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lia M. Halasz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Simon S. Lo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yolanda D. Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vyshak Venur
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jonathan T. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ABB, LPT, JJG, MB, LMH, YDT, VV: no conflicts of interest. BB: received salary and stock as an employee of Biocept. TM: Research funding: Biomimetix, Denovo Biopharma, Biohaven pharmaceuticals, Chimerix, Servier, Novocure, Vigeo. Advisory board: Servier. SSL: Member of Elekta Gamma Knife Icon Group, research support from Elekta (ended December 31, 2022), research support from Kuni Foundation, Hutchinson Center as Lead Academic Participating site, travel expenses for Japanese Society of Radiation Oncology, member of Board of Directors of Radiosurgery Society and Medical Director of Distinction in Practice in Stereotactic Radiotherapy Program, Assistant Councilor and Chair of CARROS Nominating Committee for American College of Radiology. JTY: Research funding: AstraZeneca, Kazia Therapeutics, Natera, Debiopharm, Cantex Therapeutics, Biocept; Consulting/Advisory Board: AstraZeneca, Debiopharm, Bayer, Galera Therapeutics, Nanocan Therapeutics, Plus Therapeutics, Merck

Corresponding author

Correspondence to Jonathan T. Yang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barbour, A.B., Blouw, B., Taylor, L.P. et al. Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors. J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04615-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11060-024-04615-4

Keywords

Search

Navigation