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Abstract
Objective The primary objective was to determine the sensitivity and specificity of epithelial cell adhesion molecule (EpCAM) immunoflow cytometry circulating tumor cells (CTC) analysis in CSF in patients with suspected leptomeningeal metastases (LM). The secondary objective was to explore the distribution of driver mutations in the primary tumor, plasma, cell free CSF (cfCSF), and isolated CTC from CSF in non-small cell lung cancer (NSCLC).
Methods We tested the performance of the CTC assay vs CSF cytology in a prospective study in 81 patients with a clinical suspicion of LM but a nonconfirmatory MRI. In an NSCLC subcohort, we analyzed circulating tumor (ct)DNA of the selected driver mutations by digital droplet PCR (ddPCR).
Results The sensitivity of the CTC assay was 94% (95% confidence interval [CI] 80–99) and the specificity was 100% (95% CI 91–100) at the optimal cutoff of 0.9 CTC/mL. The sensitivity of cytology was 76% (95% CI 58–89). Twelve of the 23 patients with NSCLC had mutated epidermal growth factor receptor (EGFR). All 5 tested patients with LM demonstrated the primary EGFR driver mutation in cfCSF. The driver mutation could also be detected in CTC isolated from CSF.
Conclusion CTC in CSF are detected with a high sensitivity for the diagnosis of LM. ddPCR can determine EGFR mutations in both cfCSF and isolated CTC from CSF of patients with EGFR-mutated NSCLC and LM.
Classification of evidence This study provides Class III evidence that EpCAM-based immunoflow cytometry analysis of CSF accurately identifies patients with LM.
Glossary
- cf=
- cell-free;
- CI=
- confidence interval;
- CTC=
- circulating tumor cells;
- ctDNA=
- circulating tumor DNA;
- EANO-ESMO=
- European Association of Neuro-Oncology–European Society of Medical Oncology;
- EGFR=
- epidermal growth factor receptor;
- EpCAM=
- epithelial cell adhesion molecule;
- FACS=
- fluorescence-activated cell sorting;
- FDA=
- Food and Drug Administration;
- LM=
- leptomeningeal metastases;
- LP=
- lumbar puncture;
- NSCLC=
- non-small-cell lung cancer;
- ROC=
- receiver operating characteristic;
- TKI=
- tyrosine kinase inhibitor
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received February 23, 2019.
- Accepted in final form July 24, 2019.
- © 2020 American Academy of Neurology
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