Table 1.

Comparison of Cerebrospinal Analysis Techniques for Detection and Characterization of Leptomeningeal Disease

	Conventional Cytology	CTC Analysis	ctDNA Analysis
Method	Direct visualization and identification of neoplastic cells	Detection of tumor cells in CSF based on surface molecule expression	Analysis of DNA released from tumor cells within CSF
Sensitivity	44–67% from first lumbar puncture, increased with serial testing	76–100% reported sensitivity for EpCAM-based detection	Not applicable
Availability	Wide-spread, available for all tumor types	Limited, requires use of specialized equipment and personnel.	Limited
Diagnostic Interpretation	Qualitative, can be inconclusive requiring serial lumbar punctures to establish diagnosis	Quantitative, but dependent on surface molecule expression	Not applicable
Biomarker potential	Not applicable	Potential use for monitoring treatment response and prognostication	Potential use for detecting resistance mutations or progression
Molecular genetics	Provides no information on tumor genetics	May be combined with downstream genetic testing to identify mutations and CSF clonal divergence	Can identify driver mutations and CSF clonal divergence

CTCs, circulating tumor cells; ctDNA, cell-free tumor DNA; CSF, cerebrospinal fluid; LM, leptomeningeal metastasis.