Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer
Abstract Introduction According to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell‐free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)‐resistant mechanisms (liquid rebiopsy) for lu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6870 |
| _version_ | 1827329588172161024 |
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| author | Yen‐Ting Lin Chao‐Chi Ho Wei‐Hsun Hsu Wei‐Yu Liao Ching‐Yao Yang Chong‐Jen Yu Tzu‐Hsiu Tsai James Chih‐Hsin Yang Shang‐Gin Wu Chia‐Lin Hsu Min‐Shu Hsieh Yen‐Lin Huang Chia‐Ling Wu Jin‐Yuan Shih |
| author_facet | Yen‐Ting Lin Chao‐Chi Ho Wei‐Hsun Hsu Wei‐Yu Liao Ching‐Yao Yang Chong‐Jen Yu Tzu‐Hsiu Tsai James Chih‐Hsin Yang Shang‐Gin Wu Chia‐Lin Hsu Min‐Shu Hsieh Yen‐Lin Huang Chia‐Ling Wu Jin‐Yuan Shih |
| author_sort | Yen‐Ting Lin |
| collection | DOAJ |
| description | Abstract Introduction According to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell‐free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)‐resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next‐generation sequencing (NGS). Methods We prospectively enrolled patients with lung cancer with first‐line EGFR‐TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed. Results Totally, 86 patients were enrolled. Twenty‐six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two‐thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty‐four of them were treated with osimertinib, and progression‐free survival was longer in patients without detectable T790M in cfDNA than in patients with detectable T790M in cfDNA (p = 0.02). For the 31 T790M‐negative patients, there were six with mesenchymal–epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6‐RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively. Conclusions NGS after EGFR‐TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR‐TKI resistance may find more patients with targetable cancers. |
| first_indexed | 2024-03-07T15:43:13Z |
| format | Article |
| id | doaj.art-16337db479754d2fa1ffefc1d301d9fd |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-07T15:43:13Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-16337db479754d2fa1ffefc1d301d9fd2024-03-05T06:22:52ZengWileyCancer Medicine2045-76342024-01-01131n/an/a10.1002/cam4.6870Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancerYen‐Ting Lin0Chao‐Chi Ho1Wei‐Hsun Hsu2Wei‐Yu Liao3Ching‐Yao Yang4Chong‐Jen Yu5Tzu‐Hsiu Tsai6James Chih‐Hsin Yang7Shang‐Gin Wu8Chia‐Lin Hsu9Min‐Shu Hsieh10Yen‐Lin Huang11Chia‐Ling Wu12Jin‐Yuan Shih13Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Medical Research National Taiwan University Hospital Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Medical Oncology National Taiwan University Cancer Center Taipei TaiwanDepartment of Medicine National Taiwan University Cancer Center Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital and National Taiwan University College of Medicine Taipei TaiwanDepartment of Pathology National Taiwan University Hospital Taipei TaiwanDepartment of Pathology National Taiwan University Cancer Center Taipei TaiwanACT Genomics Taipei TaiwanGraduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei TaiwanAbstract Introduction According to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell‐free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)‐resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next‐generation sequencing (NGS). Methods We prospectively enrolled patients with lung cancer with first‐line EGFR‐TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed. Results Totally, 86 patients were enrolled. Twenty‐six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two‐thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty‐four of them were treated with osimertinib, and progression‐free survival was longer in patients without detectable T790M in cfDNA than in patients with detectable T790M in cfDNA (p = 0.02). For the 31 T790M‐negative patients, there were six with mesenchymal–epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6‐RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively. Conclusions NGS after EGFR‐TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR‐TKI resistance may find more patients with targetable cancers.https://doi.org/10.1002/cam4.6870EGFR mutationEGFR‐TKI resistancenext‐generation sequencingNSCLC |
| spellingShingle | Yen‐Ting Lin Chao‐Chi Ho Wei‐Hsun Hsu Wei‐Yu Liao Ching‐Yao Yang Chong‐Jen Yu Tzu‐Hsiu Tsai James Chih‐Hsin Yang Shang‐Gin Wu Chia‐Lin Hsu Min‐Shu Hsieh Yen‐Lin Huang Chia‐Ling Wu Jin‐Yuan Shih Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer Cancer Medicine EGFR mutation EGFR‐TKI resistance next‐generation sequencing NSCLC |
| title | Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer |
| title_full | Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer |
| title_fullStr | Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer |
| title_full_unstemmed | Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer |
| title_short | Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer |
| title_sort | tissue or liquid rebiopsy a prospective study for simultaneous tissue and liquid ngs after first line egfr inhibitor resistance in lung cancer |
| topic | EGFR mutation EGFR‐TKI resistance next‐generation sequencing NSCLC |
| url | https://doi.org/10.1002/cam4.6870 |
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