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Journal of Cancer Research and Clinical Oncology

Erschienen in:

23.07.2020 | Original Article – Clinical Oncology

A nanowire-based liquid biopsy method using cerebrospinal fluid cell-free DNA for targeted management of leptomeningeal carcinomatosis

verfasst von: Wonyoung Choi, Youngnam Cho, Seog-Yun Park, Kum Hui Hwang, Ji-Youn Han, Youngjoo Lee

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2021

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Abstract

Purpose

This study aimed to evaluate whether genotyping cell free DNA (cfDNA) in the cerebrospinal fluid (CSF) may be helpful in managing leptomeningeal carcinomatosis (LMC) of EGFR-mutant non-small cell lung cancer (NSCLC).

Methods

Patients with EGFR-mutant NSCLC who progressed as LMC after 3rd-generation tyrosine kinase inhibitors (EGFR–TKIs) were evaluated. A nanowire-based cfDNA assay was performed for genotyping cfDNA from the CSF and plasma. We focused on de novo EGFR C797S mutation and MET amplification, which are the most common mechanisms of resistance to 3rd-generation EGFR–TKIs.

Results

Among 11 patients, five (45.5%) had progression only at the leptomeninges. The tumor-associated CSF-cfDNA was identified in eight (72.7%) patients, and plasma-cfDNA in six (54.5%) patients. In the CSF-cfDNA, EGFR C797S mutation and MET amplification were detected in four (36.3%) and two (18.2%) patients, respectively. Of four patients with the C797S-positive LMC, only one had concurrent CSF-T790M mutation. Three patients who had the C797S-positive LMC without CSF-T790M mutation, received 1st–2nd generation EGFR–TKIs and showed clinical benefits for 20.8, 17.8, and 8.8 weeks, respectively. Serial assessment with cfDNA in these patients demonstrated that the CSF levels of C797S mutation were decreased with radiological or neurological improvement but the plasma levels of T790M mutation were markedly increased before objective progression.

Conclusion

Genotyping CSF-cfDNA by the nanowire-based assay is feasible and effective in guiding the treatment of LMC in patients with EGFR-mutant NSCLC.

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Titel: A nanowire-based liquid biopsy method using cerebrospinal fluid cell-free DNA for targeted management of leptomeningeal carcinomatosis
verfasst von: Wonyoung Choi
Youngnam Cho
Seog-Yun Park
Kum Hui Hwang
Ji-Youn Han
Youngjoo Lee
Publikationsdatum: 23.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03324-5

Springer Medizin

A nanowire-based liquid biopsy method using cerebrospinal fluid cell-free DNA for targeted management of leptomeningeal carcinomatosis