Application of liquid biopsy-based targeted capture sequencing analysis to improve the precision treatment of non-small cell lung cancer by tyrosine kinase inhibitors
Bibliographic record
Abstract
Background Targeted therapy of patients with non-small cell lung cancer (NSCLC) who harbour sensitising mutations by tyrosine kinase inhibitors (TKIs) has been found more effective than traditional chemotherapies. However, target genes status (eg, epidermal growth factor receptor ( EGFR ) TKIs sensitising and resistant mutations) need to be tested for choosing appropriate TKIs. This study is to investigate the performance of a liquid biopsy-based targeted capture sequencing assay on the molecular analysis of NSCLC. Methods Plasma samples from patients with NSCLC who showed resistance to the first/second-generation EGFR TKIs treatment were collected. The AVENIO ctDNA Expanded Kit is a 77 pan-cancer genes detection assay that was used for detecting EGFR TKIs resistance-associated gene mutations. Through comparison of the EGFR gene testing results from the Cobas EGFR Mutation Test v2, and UltraSEEK Lung Panel, the effectiveness of the targeted capture sequencing assay was verified. Results A total of 24 plasma cell-free DNA (cfDNA) samples were tested by the targeted capture sequencing assay. 33.3% (8/24) cfDNA samples were positive for EGFR exon 20 p.T790M which leads to EGFR dependent TKIs resistance. 8.3% (2/24) and 4.2% (1/24) samples were positive for mesenchymal-epithelial transition gene amplification and B‐Raf proto‐oncogene, serine/threonine kinase exon 15 p.V600E mutations which lead to EGFR independent TKIs resistance. The median value of the p.T790M variant allele fraction and variant copy numbers was 2% and 36.10 copies/mL plasma, respectively. The next-generation sequencing test showed higher than 90% concordance with either MassArray or qPCR-based methods for detecting either EGFR TKIs sensitising or resistance mutations. Conclusion The targeted capture sequencing test can support comprehensive molecular analysis needed for TKIs treatment, which is promising to be clinically applied for the improved precision treatment of NSCLC.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".