Therapy Monitoring of EGFR-Positive Non-Small Cell Lung Cancer Patients Using ddPCR Multiplex Assays

Remco de Kock (Corresponding author), Ben van den Borne, Maggy Youssef- El Soud, Huub Belderbos, Luc Brunsveld, Volkher Scharnhorst, Birgit Deiman

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

The detection of EGFR-sensitizing and EGFR-resistance mutations in advanced non-small-cell lung cancer patients is important for the selection and monitoring of EGFR tyrosine-kinase inhibitor therapy. Droplet digital PCR (ddPCR) multiplex assays allow for sensitive and simultaneous detection of multiple mutations in cell-free DNA (cfDNA) with a minimum of extract needed and at lower cost. Patients were screened for the EGFR tyrosine-kinase inhibitor-sensitizing mutations Ex19Del, L858R, L861Q, G719S, and S768I using a novel ddPCR pentaplex assay. Patients who tested positive subsequently were monitored during treatment for the EGFR-sensitizing mutation and two EGFR-resistance mutations, T790M and C797S, using a ddPCR monitor triplex assay. The ddPCR multiplex assays enabled reliable detection of each mutation with a fractional abundance of at least 0.1%. For six patients, longitudinal data were analyzed and the ddPCR results provided a good reflection of the course of the disease and radiologic response. This study confirms that ddPCR on cfDNA supports the diagnosis and therapy selection, and shows that ddPCR multiplex assays on cfDNA could be a valuable additional diagnostic tool for therapy monitoring of non-small-cell lung cancer patients.

Original languageEnglish
Pages (from-to)495-505
Number of pages11
JournalThe Journal of Molecular Diagnostics
Volume23
Issue number4
Early online date21 Jan 2021
DOIs
Publication statusPublished - Apr 2021

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