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ID 115668
Author
Hanibuchi, Masaki Tokushima University|Shikoku Central Hospital of the Mutual Aid Association of Public School Teachers KAKEN Search Researchers
Kanoh, Akira Taiho Pharmaceutical
Kuramoto, Takuya Taiho Pharmaceutical
Saito, Tatsuro Riken Genesis
Kozai, Hiroyuki Tokushima University
Kondo, Mayo Tokushima University
Keywords
non-small cell lung cancer
circulating free DNA
epidermal growth factor receptor mutation
epidermal growth factor receptor-tyrosine kinase inhibitor
Content Type
Journal Article
Description
The feasibility and required sensitivity of circulating free DNA (cfDNA)-based detection methods in second-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment are not well elucidated. We examined T790M and other activating mutations of EGFR by cfDNA to assess the clinical usability. In 45 non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations, cfDNAs were prepared from the plasma samples. EGFR mutations in cfDNA were detected using highly sensitive methods and originally developed assays and these results were compared to tissue-based definitive diagnoses. The specificity of each cfDNA-based method ranged 96–100% whereas the sensitivity ranged 56–67%, indicating its low pseudo-positive rate. In EGFR-TKI failure cohort, 41–46% samples were positive for T790M by each cfDNA-based method, which was comparable to re-biopsy tissue-based T790M positive rates in literature. The concordance of the results for each EGFR mutation ranged from 83–95%. In eight patients, the results of the cfDNA-based assays and re-biopsy-derived tissue-based test were compared. The observed overall agreement ranged in 50–63% in T790M, and in 63–100% in activating EGFR mutations. In this study, we have newly developed three types of assay which have enough sensitivity to detect cfDNA. We also detected T790M in 44% of patients who failed prior EGFR-TKI treatment, indicating that cfDNA-based assay has clinical relevance for detecting acquired mutations of EGFR.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
10
Issue
38
Start Page
3654
End Page
3666
Published Date
2019-06-04
Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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language
eng
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departments
Medical Sciences
University Hospital