Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer Journal Article


Authors: Malani, R.; Fleisher, M.; Kumthekar, P.; Lin, X.; Omuro, A.; Groves, M. D.; Lin, N. U.; Melisko, M.; Lassman, A. B.; Jeyapalan, S.; Seidman, A.; Skakodub, A.; Boire, A.; DeAngelis, L. M.; Rosenblum, M.; Raizer, J.; Pentsova, E.
Article Title: Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer
Abstract: Purpose: The CellSearch® system has been used to identify circulating tumor cells (CTCs) in cerebrospinal fluid (CSF) to diagnose leptomeningeal metastasis (LM) in patients with epithelial cancers. Using this system, we prospectively explored sequential CSF CTC enumeration in patients with LM from HER2+ cancers receiving intrathecal (IT) trastuzumab to capture dynamic changes in CSF CTC enumeration. Methods: CSF from patients enrolled in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was obtained on day 1 of each cycle and was evaluated by the CellSearch® platform for CTC enumeration. The results were correlated with CSF cytology from the same sample, along with clinical and radiographic response. Results: Fifteen out of 34 patients with HER2+ LM were enrolled in CSF CTC analysis; 14 were women. Radiographic LM was documented in 14 (93%) patients; CSF cytology was positive in 6 (40%) and CSF CTCs were identified in 13 (87%). Median CSF CTC was 22 CTCs (range 0–200 +) per 3 ml. HER2/neu expression analysis of CTCs was performed in 8 patients; 75% had confirmed expression of HER2/neu positivity in CSF and HER2/neu expression was absent in 25%. Four of 10 patients received 7 or more cycles of IT trastuzumab; in 3 of these patients, increase in CSF CTCs enumeration from baseline was detected 2–3 months prior to changes seen on MRI, and while CSF cytology remained negative. Conclusion: Our study demonstrates that enumeration of CSF CTCs may provide dynamic, quantitative assessment of tumor burden in the central nervous system compartment during treatment for LM and prior to changes on MRI or CSF cytology. Trial Registration: Clinicaltrials.gov: NCT01325207; registered March 29th, 2011. © 2020, The Author(s).
Keywords: cerebrospinal fluid; biomarker; circulating tumor cells; leptomeningeal metastases; liquid biomarkers
Journal Title: Journal of Neuro-Oncology
Volume: 148
Issue: 3
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2020-07-01
Start Page: 599
End Page: 606
Language: English
DOI: 10.1007/s11060-020-03555-z
PUBMED: 32506369
PROVIDER: scopus
PMCID: PMC7438284
DOI/URL:
Notes: Article -- Export Date: 1 September 2020 -- Source: Scopus
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MSK Authors
  1. Andrew D Seidman
    295 Seidman
  2. Marc Rosenblum
    373 Rosenblum
  3. Antonio Marcilio Padula Omuro
    198 Omuro
  4. Martin Fleisher
    301 Fleisher
  5. Adrienne Boire
    57 Boire
  6. Xuling   Lin
    15 Lin
  7. Rachna Malani
    23 Malani