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Research article
Yuichiro Takeda
National Center for Global Health and Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1412-646X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than first-generation EGFR-TKIs used for first-line treatment, their efficacy for long-term patient survival remains unclear even upon administration of a complete sequence of EGFR-TKI therapy, and limited information is available regrading genetic diagnostic approaches after EGFR-TKI naïve treatment. This study aimed to investigate the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy among these patients.
Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs except for osimertinib, single plexus COBAS version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy.
Results: From April 2016 through May 2019, 113 patients harbored EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, displayed a new lesion, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at rare sites.
Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors, and these biopsies can be repeated numerous times.
Keywords
T790M, Repeating biopsy, single plexus PCR, positive factors on T790M
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CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 16 Sep, 2020
Editor assigned
On 14 Sep, 2020
Submission checks complete
On 13 Sep, 2020
Editor invited
On 13 Sep, 2020
No comments provided
Reviewer #2 agreed
On 18 Aug, 2020
Reviewer #1 agreed
On 12 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Reviewers invited
Invitations sent on 11 Aug, 2020
Editor assigned
On 03 Aug, 2020
Submission checks complete
On 02 Aug, 2020
Editor invited
On 02 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 24 Jul, 2020
Editor assigned
On 23 Jul, 2020
Editor invited
On 22 Jul, 2020
Submission checks complete
On 18 Jul, 2020
Version 1
Posted 31 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 02 Jul, 2020
Review #1 received
Received 21 Jun, 2020
Reviewer #1 agreed
On 19 Jun, 2020
Reviewers invited
Invitations sent on 06 Apr, 2020
First submitted
On 25 Mar, 2020
Editor assigned
On 25 Mar, 2020
Submission checks complete
On 24 Mar, 2020
Editor invited
On 24 Mar, 2020
Metrics
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PDF Downloads: ...
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Subject Areas
Oncology
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A new preprint design is coming!
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See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Yuichiro Takeda
National Center for Global Health and Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1412-646X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Editorial decision: Accept
On 16 Sep, 2020
Editor assigned
On 14 Sep, 2020
Submission checks complete
On 13 Sep, 2020
Editor invited
On 13 Sep, 2020
No comments provided
Reviewer #2 agreed
On 18 Aug, 2020
Reviewer #1 agreed
On 12 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Reviewers invited
Invitations sent on 11 Aug, 2020
Editor assigned
On 03 Aug, 2020
Submission checks complete
On 02 Aug, 2020
Editor invited
On 02 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 24 Jul, 2020
Editor assigned
On 23 Jul, 2020
Editor invited
On 22 Jul, 2020
Submission checks complete
On 18 Jul, 2020
Version 1
Posted 31 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 02 Jul, 2020
Review #1 received
Received 21 Jun, 2020
Reviewer #1 agreed
On 19 Jun, 2020
Reviewers invited
Invitations sent on 06 Apr, 2020
First submitted
On 25 Mar, 2020
Editor assigned
On 25 Mar, 2020
Submission checks complete
On 24 Mar, 2020
Editor invited
On 24 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Oncology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than first-generation EGFR-TKIs used for first-line treatment, their efficacy for long-term patient survival remains unclear even upon administration of a complete sequence of EGFR-TKI therapy, and limited information is available regrading genetic diagnostic approaches after EGFR-TKI naïve treatment. This study aimed to investigate the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy among these patients.
Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs except for osimertinib, single plexus COBAS version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy.
Results: From April 2016 through May 2019, 113 patients harbored EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, displayed a new lesion, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at rare sites.
Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors, and these biopsies can be repeated numerous times.
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
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