Cerebrospinal fluid circulating tumor cells: A novel tool to diagnose leptomeningeal metastases from epithelial tumors Journal Article


Authors: Lin, X.; Fleisher, M.; Rosenblum, M.; Lin, O.; Boire, A.; Briggs, S.; Bensman, Y.; Hurtado, B.; Shagabayeva, L.; DeAngelis, L. M.; Panageas, K. S.; Omuro, A.; Pentsova, E. I.
Article Title: Cerebrospinal fluid circulating tumor cells: A novel tool to diagnose leptomeningeal metastases from epithelial tumors
Abstract: Background: Diagnosis of leptomeningeal metastasis (LM) remains challenging due to low sensitivity of CSF cytology and infrequent unequivocal MRI findings. In a previous pilot study, we showed that rare cell capture technology (RCCT) could be used to detect circulating tumor cells (CTC) in the CSF of patients with LM from epithelial tumors. To establish the diagnostic accuracy of CSF-CTC in the diagnosis of LM, we applied this technique in a distinct, larger cohort of patients. Methods: In this institutional review board-approved prospective study, patients with epithelial tumors and clinical suspicion of LM underwent CSF-CTC evaluation and standard MRI and CSF cytology examination. CSF-CTC enumeration was performed through an FDA-approved epithelial cell adhesion molecule-based RCCT immunomagnetic platform. LM was defined by either positive CSF cytology or imaging positive for LM. ROC analysis was utilized to define an optimal cutoff for CSF-CTC enumeration. Results: Ninety-five patients were enrolled (36 breast, 31 lung, 28 others). LM was diagnosed in 30 patients (32%) based on CSF cytology (n = 12), MRI findings (n = 2), or both (n = 16). CSF-CTC were detected in 43/95 samples (median 19.3 CSF-CTC/mL, range 0.3 to 66.7). Based on ROC analysis, 1 CSF-CTC/mL provided the best threshold to diagnose LM, achieving a sensitivity of 93%, specificity of 95%, positive predictive value 90%, and negative predictive value 97%. Conclusions: We defined ≥1 CSF-CTC/mL as the optimal cutoff for diagnosis of LM. CSF-CTC enumeration through RCCT is a robust tool to diagnose LM and should be considered in the routine LM workup in solid tumor patients. © 2017 The Author(s).
Keywords: cerebrospinal fluid; circulating tumor cells; leptomeningeal metastases
Journal Title: Neuro-Oncology
Volume: 19
Issue: 9
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2017-09-01
Start Page: 1248
End Page: 1254
Language: English
DOI: 10.1093/neuonc/nox066
PROVIDER: scopus
PMCID: PMC5570249
PUBMED: 28821205
DOI/URL:
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    373 Rosenblum
  2. Oscar Lin
    275 Lin
  3. Antonio Marcilio Padula Omuro
    198 Omuro
  4. Katherine S Panageas
    428 Panageas
  5. Martin Fleisher
    301 Fleisher
  6. Adrienne Boire
    57 Boire
  7. Samuel Royden Briggs
    18 Briggs
  8. Xuling   Lin
    15 Lin