Utility of Cerebrospinal Fluid Cell-Free DNA in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis

Abstract

Background

Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small-cell lung cancer (NSCLC).

Objective

The aim of this study was to evaluate the utility of cerebrospinal fluid (CSF) as a medium for epidermal growth factor receptor (EGFR) mutation testing in clinical practice.

Patients and methods

We prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing.

Results

Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%.

Conclusions

For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information.

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Affiliations

Authors

Corresponding author

Correspondence to Chao-Hua Chiu.

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Funding

This work was supported by the Ministry of Science and Technology, Taiwan (Grant number MOST106-2314-B-075-031-MY), Ministry of Health and Welfare, Taiwan (Grant number MOHW109-TDU-B-211-134019), and Taipei Veterans General Hospital (Grant number V110B-008).

Conflict of interest

CLC has received honoraria from AstraZeneca, Boehringer Ingelheim, and Roche. YHL has received honoraria from AstraZeneca, Boehringer Ingelheim, and Pfizer. THS has received honoraria from Boehringer Ingelheim and Novartis. YMC has received honoraria from Boehringer Ingelheim, Eli Lilly, Roche/Genentech/Chugai, MSD, Pfizer, Novartis, BMS, Ono Pharmaceutical, AstraZeneca, and Takeda Oncology; and served as advisor for Boehringer Ingelheim, Eli Lilly, Roche/Chugai, MSD, AstraZeneca, and Takeda Oncology. CHC has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, and Roche. The other authors declare no conflicts of interest that might be relevant to the contents of this article.

Ethics approval

The Institutional Review Board of Taipei Veterans General Hospital approved this study.

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Data availability

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Author contributions

Conceptualization: CLC, CHC, YMC, TYC. Data collection, experiment, and analysis: CCL, CHW, HCH, YCY, CIS, YHL, THS. Statistics: CLC, HJC, YTH. First draft preparation: CLC, CHC. Review and final approval: all authors.

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Chiang, CL., Lee, CC., Huang, HC. et al. Utility of Cerebrospinal Fluid Cell-Free DNA in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis. Targ Oncol 16, 207–214 (2021). https://doi.org/10.1007/s11523-021-00791-9

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