Abstract
Simple SummaryLiquid biopsy is a useful tool during longitudinal monitoring of NSCLC patients and requires highly sensitive and reliable technologies for accurate detection of genomic alterations. We evaluated and used crystal digital PCR to detect and quantify EGFR mutations in plasma cfDNA and paired CTCs of NSCLC patients before treatment with osimertinib and at progression of disease.Circulating tumor DNA (ctDNA) analysis has clinical utility in EGFR mutant NSCLC. Circulating tumor cells (CTCs) consist a unique source of information at the cellular level. Digital PCR (dPCR) is a valuable tool for accurate and valid analysis of gene mutations in liquid biopsy analysis. In the present study we detected EGFR mutations in ctDNA and paired CTCs under osimertinib therapy at two time points using crystal dPCR and the naica® system (Stilla Technologies). We quantified mutation allele frequencies (MAF) of EGFR mutations in 91 plasma cfDNA samples of 48 EGFR mutant NSCLC patients and in 64 matched CTC-derived genomic DNA samples, and the FDA-cleared cobas® EGFR mutation test in 80 identical plasma samples. Direct comparison between crystal dPCR and the cobas EGFR assay revealed a high concordance for all EGFR mutations. Our comparison of crystal dPCR results in ctDNA with the corresponding primary tissue has shown a strong correlation. EGFR mutations analysis in paired CTC-derived gDNA revealed a high heterogeneity. Crystal dPCR offers the unique advantages of high analytical sensitivity, precision, and accuracy for detecting and quantifying multiple EGFR mutations in plasma cfDNA and CTCs of NSCLC patients.
Highlights
Introduction iationsThe non-small cell lung cancer (NSCLC) treatment landscape has changed through the last two decades [1] and several clinical trials have revealed significantly improved progression-free survival (PFS) and overall survival (OS) [2,3,4,5]
20 T790M EGFR mutation [6] and was treated with the administration of osimertinib [7], a 3rd generation EGFR TKI which was proved to be effective against both T790M and sensitizing mutations [8]
The management of EGFR mutant NSCLC has successfully switched from chemotherapy to targeted treatment improving substantially the survival outcomes of NSCLC patients [39]
Summary
Introduction iationsThe non-small cell lung cancer (NSCLC) treatment landscape has changed through the last two decades [1] and several clinical trials have revealed significantly improved progression-free survival (PFS) and overall survival (OS) [2,3,4,5]. The progression of disease due to the emergence of different resistance mechanisms was always a challenge to overcome. The most common resistance mechanism to 1st or 2nd generation inhibitors of the tyrosine kinase domain of epidermal growth factor receptor (EGFR TKIs) is the presence of exon. 20 T790M EGFR mutation [6] and was treated with the administration of osimertinib [7], a 3rd generation EGFR TKI which was proved to be effective against both T790M and sensitizing mutations [8]. Despite the rationale of EGFR TKI treatment sequence, in 2018, the US Food and Drug Administration (FDA) approved osimertinib as a 1st line treatment.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
