Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma
Background Circulating tumor DNA (ctDNA) is a biomarker for the selection of target agents in various malignancies. In this study, we examined the effect of ctDNA presence on the response to EGFR‐tyrosine kinase inhibitor (TKI) and on the prognosis in lung adenocarcinoma. Methods ctDNA of EGFR‐TKI s...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.13219 |
| _version_ | 1818032146111004672 |
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| author | Taehee Kim Eun Young Kim Sang Hoon Lee Do Sun Kwon Arum Kim Yoon Soo Chang |
| author_facet | Taehee Kim Eun Young Kim Sang Hoon Lee Do Sun Kwon Arum Kim Yoon Soo Chang |
| author_sort | Taehee Kim |
| collection | DOAJ |
| description | Background Circulating tumor DNA (ctDNA) is a biomarker for the selection of target agents in various malignancies. In this study, we examined the effect of ctDNA presence on the response to EGFR‐tyrosine kinase inhibitor (TKI) and on the prognosis in lung adenocarcinoma. Methods ctDNA of EGFR‐TKI sensitizing mutations (mEGFR), L858R substitution and Exon 19 deletion (E19d) mutation, was evaluated using droplet digital PCR (ddPCR) in 81 patients with lung adenocarcinoma which harbored mEGFR in the corresponding tumor tissues. Results The study recruited lung cancer patients at various stages, and the sensitivity, specificity, and area under the curve (AUC) of mEGFR ctDNA detection by ddPCR were 40.0%, 88.5%, and 0.68, respectively. It showed higher sensitivity (75.0% vs. 10.0%) and AUC (0.83 vs. 0.49) in the advanced stages of lung adenocarcinoma compared with the early stages and the number of metastases and the fractional abundance of mEGFR ctDNA showed a strong correlation (σ = 0.516; P < 0.001, Spearman correlation test). There was a significantly shorter progression‐free survival and duration of disease control by EGFR‐TKIs in the ctDNA‐positive group than the negative group (14.0 vs. 41.0 months, P = 0.02 and 12.0 vs. 23.0 months, P = 0.02, log‐rank test, respectively). There was a trend for overall survival time to be shorter in patients with mEGFR ctDNA than for patients without mEGFR ctDNA (35.6 vs. 67.1 months, P = 0.06, log‐rank test). Conclusions These data showed that mEGFR ctDNA detection using ddPCR is useful in the advanced stages and its presence predicted distant metastasis and poor clinical outcome in lung adenocarcinoma. |
| first_indexed | 2024-12-10T06:02:44Z |
| format | Article |
| id | doaj.art-2ceb9cbe892b4ae1814bcd6b29a317be |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-12-10T06:02:44Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-2ceb9cbe892b4ae1814bcd6b29a317be2022-12-22T01:59:47ZengWileyThoracic Cancer1759-77061759-77142019-12-0110122267227310.1111/1759-7714.13219Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinomaTaehee Kim0Eun Young Kim1Sang Hoon Lee2Do Sun Kwon3Arum Kim4Yoon Soo Chang5Department of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul Republic of KoreaBackground Circulating tumor DNA (ctDNA) is a biomarker for the selection of target agents in various malignancies. In this study, we examined the effect of ctDNA presence on the response to EGFR‐tyrosine kinase inhibitor (TKI) and on the prognosis in lung adenocarcinoma. Methods ctDNA of EGFR‐TKI sensitizing mutations (mEGFR), L858R substitution and Exon 19 deletion (E19d) mutation, was evaluated using droplet digital PCR (ddPCR) in 81 patients with lung adenocarcinoma which harbored mEGFR in the corresponding tumor tissues. Results The study recruited lung cancer patients at various stages, and the sensitivity, specificity, and area under the curve (AUC) of mEGFR ctDNA detection by ddPCR were 40.0%, 88.5%, and 0.68, respectively. It showed higher sensitivity (75.0% vs. 10.0%) and AUC (0.83 vs. 0.49) in the advanced stages of lung adenocarcinoma compared with the early stages and the number of metastases and the fractional abundance of mEGFR ctDNA showed a strong correlation (σ = 0.516; P < 0.001, Spearman correlation test). There was a significantly shorter progression‐free survival and duration of disease control by EGFR‐TKIs in the ctDNA‐positive group than the negative group (14.0 vs. 41.0 months, P = 0.02 and 12.0 vs. 23.0 months, P = 0.02, log‐rank test, respectively). There was a trend for overall survival time to be shorter in patients with mEGFR ctDNA than for patients without mEGFR ctDNA (35.6 vs. 67.1 months, P = 0.06, log‐rank test). Conclusions These data showed that mEGFR ctDNA detection using ddPCR is useful in the advanced stages and its presence predicted distant metastasis and poor clinical outcome in lung adenocarcinoma.https://doi.org/10.1111/1759-7714.13219ctDNAddPCRlung adenocarcinomamEGFR |
| spellingShingle | Taehee Kim Eun Young Kim Sang Hoon Lee Do Sun Kwon Arum Kim Yoon Soo Chang Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma Thoracic Cancer ctDNA ddPCR lung adenocarcinoma mEGFR |
| title | Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma |
| title_full | Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma |
| title_fullStr | Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma |
| title_full_unstemmed | Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma |
| title_short | Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma |
| title_sort | presence of megfr ctdna predicts a poor clinical outcome in lung adenocarcinoma |
| topic | ctDNA ddPCR lung adenocarcinoma mEGFR |
| url | https://doi.org/10.1111/1759-7714.13219 |
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