Lung cancer (Amsterdam, Netherlands)
via Europe PMC
Molecular concordance and clonal dynamics of KRAS mutations in lung adenocarcinoma across distinct clinical scenarios.
Zhao D, Xie D, Zhang L, +7 more, Che N
AI summary — for doctors, generated from the abstract only
KRAS mutations were often discordant between multiple lung lesions, which can help tell separate primaries from metastases.
What was studied
Analysis of 108 lung adenocarcinoma patients with paired NGS tests, grouped by same-lesion serial sampling, synchronous multiple primaries and longitudinal sampling of distinct lesions.
Key findings
- KRAS retention was 100% in untreated same-lesion pairs and 83.3% after neoadjuvant therapy.
- 80% of synchronous multifocal cases were molecularly discordant.
- Concordance was lower between a primary and a new lung lesion than between primary and metastasis (65.5% vs 88.5%).
Clinical relevance
Suggests repeat KRAS testing can change interpretation in multifocal disease and in the G12C inhibitor era.
Who should care
Limitations
Retrospective and small subgroups, with the abstract cut off.
Consider repeat molecular testing when lesions behave differently or distinguishing primaries from metastases matters.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
BACKGROUND
Following the approval of KRAS G12C inhibitors, the necessity of serial KRAS testing remains debated. This study evaluates the molecular concordance and dynamic evolution of KRAS mutations across different clinical scenarios and explores their diagnostic utility in differentiating multiple primary lung cancers (MPLCs) from intra-pulmonary metastases.
METHODS
A total of 108 patients with paired NGS tests and ≥ 1 KRAS-positive result were categorized into three groups: Group A (same lesion sampled longitudinally, n = 16; stratified by neoadjuvant therapy status), Group B (synchronous MPLCs, n = 30), and Group C (longitudinal monitoring of distinct lesions, n = 62). Group C was further stratified into three subgroups based on lesion relationships: metastasis-to-metastasis (C1), primary-to-metastasis (C2), and primary-to-new pulmonary lesion (C3).
RESULTS
In Group A, the intra-lesional KRAS retention rate was 100% in upfront surgery without prior treatment, but decreased to 83.3% after neoadjuvant therapy. In Group B, 80.0% (24/30) of multifocal cases exhibited inter-lesion molecular discordance, including 7 cases with distinct KRAS amino acid subtypes that confirmed synchronous MPLCs. In Group C, molecular concordance was significantly lower between primary and new pulmonary lesions (C3) than between primary and metastatic lesions (C2) (65.5% vs. 88.5%, P = 0.046). Baseline variant allele frequency (VAF) served as a strong predictor of subsequent KRAS loss (median VAF: 8.4% vs. 22.4%, P = 0.031). Furthermore, patients with co-mutations of EGFR and KRAS were more prone to experience KRAS loss than those with isolated KRAS mutations (70.0% vs. 12.0%, P < 0.001).
CONCLUSIONS
KRAS mutations display scenario-dependent concordance, remaining clonally stable in true metastases while exhibiting divergence in independent primary lesions or under therapeutic selection. Repeat NGS testing should be prioritized for patients presenting with new or multifocal pulmonary lesions, lower baseline KRAS VAF, or co-occurring EGFR mutations.
DOI
10.1016/j.lungcan.2026.109597
PMID
42731561
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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