Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study

Abstract Background This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. Methods This prospective, multicenter, observational study included 30 patients with non-sma...

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Main Authors: Hiroaki Fujii, Hideyuki Nagakura, Nobuaki Kobayashi, Sousuke Kubo, Katsushi Tanaka, Keisuke Watanabe, Nobuyuki Horita, Yu Hara, Masanori Nishikawa, Kenji Miura, Harumi Koizumi, Yu Ito, Motofumi Tsubakihara, Naoki Miyazawa, Makoto Kudo, Masaharu Shinkai, Takeshi Kaneko
Format: Article
Language:English
Published: BMC 2022-10-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-022-10135-z
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author Hiroaki Fujii
Hideyuki Nagakura
Nobuaki Kobayashi
Sousuke Kubo
Katsushi Tanaka
Keisuke Watanabe
Nobuyuki Horita
Yu Hara
Masanori Nishikawa
Kenji Miura
Harumi Koizumi
Yu Ito
Motofumi Tsubakihara
Naoki Miyazawa
Makoto Kudo
Masaharu Shinkai
Takeshi Kaneko
author_facet Hiroaki Fujii
Hideyuki Nagakura
Nobuaki Kobayashi
Sousuke Kubo
Katsushi Tanaka
Keisuke Watanabe
Nobuyuki Horita
Yu Hara
Masanori Nishikawa
Kenji Miura
Harumi Koizumi
Yu Ito
Motofumi Tsubakihara
Naoki Miyazawa
Makoto Kudo
Masaharu Shinkai
Takeshi Kaneko
author_sort Hiroaki Fujii
collection DOAJ
description Abstract Background This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. Methods This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. Results Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. Conclusions Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.
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spelling doaj.art-0d1ed5d6ba3e4abdb7bde272134266792022-12-22T04:30:06ZengBMCBMC Cancer1471-24072022-10-0122111110.1186/s12885-022-10135-zLiquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective studyHiroaki Fujii0Hideyuki Nagakura1Nobuaki Kobayashi2Sousuke Kubo3Katsushi Tanaka4Keisuke Watanabe5Nobuyuki Horita6Yu Hara7Masanori Nishikawa8Kenji Miura9Harumi Koizumi10Yu Ito11Motofumi Tsubakihara12Naoki Miyazawa13Makoto Kudo14Masaharu Shinkai15Takeshi Kaneko16Department of Pulmonology, Yokohama City University Graduate School of MedicineDepartment of Internal Medicine, Yokohama Ekisaikai HospitalDepartment of Pulmonology, Yokohama City University Graduate School of MedicineRespiratory Disease Center, Yokohama City University Medical CenterDepartment of Pulmonology, Yokohama City University Graduate School of MedicineDepartment of Pulmonology, Yokohama City University Graduate School of MedicineDepartment of Pulmonology, Yokohama City University Graduate School of MedicineDepartment of Pulmonology, Yokohama City University Graduate School of MedicineDepartment of Pulmonology, Fujisawa City HospitalDepartment of Pulmonology, Yokohama Sakae Kyosai HospitalDepartment of Pulmonology, Yokohama Minami Kyosai HospitalDepartment of Pulmonology, Yokohama Rosai HospitalDepartment of Pulmonology, National Hospital Organization Yokohama Medical CenterDepartment of Pulmonology, Saiseikai Yokohamashi Nanbu HospitalRespiratory Disease Center, Yokohama City University Medical CenterDepartment of Respiratory Medicine, Tokyo Shinagawa HospitalDepartment of Pulmonology, Yokohama City University Graduate School of MedicineAbstract Background This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. Methods This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. Results Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. Conclusions Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.https://doi.org/10.1186/s12885-022-10135-zCell-free deoxyribonucleic acidEpidermal growth factor receptorLiquid biopsyNon-small cell lung cancerSecond-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
spellingShingle Hiroaki Fujii
Hideyuki Nagakura
Nobuaki Kobayashi
Sousuke Kubo
Katsushi Tanaka
Keisuke Watanabe
Nobuyuki Horita
Yu Hara
Masanori Nishikawa
Kenji Miura
Harumi Koizumi
Yu Ito
Motofumi Tsubakihara
Naoki Miyazawa
Makoto Kudo
Masaharu Shinkai
Takeshi Kaneko
Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
BMC Cancer
Cell-free deoxyribonucleic acid
Epidermal growth factor receptor
Liquid biopsy
Non-small cell lung cancer
Second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
title Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
title_full Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
title_fullStr Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
title_full_unstemmed Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
title_short Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study
title_sort liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non small cell lung cancer treated with afatinib a multicenter prospective study
topic Cell-free deoxyribonucleic acid
Epidermal growth factor receptor
Liquid biopsy
Non-small cell lung cancer
Second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
url https://doi.org/10.1186/s12885-022-10135-z
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