Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non–Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data: Hayoung Seong, Soo Han Kim, Mi-Hyun Kim, Ahrong Kim, Ju Sun Song, Jung Seop Eom; Cancer Res Treat. 2026;58(3):738-747. Published online August 25, 2025; DOI: https://doi.org/10.4143/crt.2025.114

Abstract PDF Supplementary Material PubReader ePub: Purpose
Comprehensive genomic profiling of early-stage non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This study aimed to investigate genomic profiles of early- and advanced-stage EGFR-mutant NSCLC and identify potential innate resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs) using targeted next-generation sequencing (NGS).
Materials and Methods
This retrospective observational study analyzed genomic profiles of patients with early-stage (IA-IIIA) and advanced-stage (IIIB-IV) EGFR-mutant NSCLC from the Lung Cancer NGS registry. Targeted NGS was performed to assess concurrent genetic alterations (GAs), tumor mutational burden (TMB), and variant allele frequency (VAF) of EGFR mutations.
Results
Overall, 160 patients (100 early-stage and 60 advanced-stage) were analyzed. The proportion of patients with concurrent GAs was not significantly different between stages (82.0% vs. 91.7%, p=0.092). Median TMB was 3.8 mutations/Mb in both stages, with no significant difference (p=0.206). However, the median VAF of EGFR mutations was significantly lower in early-stage compared to that in advanced-stage (19.3% vs. 29.6%, p=0.002). While TMB remained unchanged with disease progression (p=0.192), VAF of EGFR mutations increased significantly (p < 0.001). Moreover, the frequencies of concurrent single nucleotide variants and copy number variants were significantly lower in early-stage NSCLC.
Conclusion
Genomic heterogeneity in EGFR-mutant NSCLC arises early in tumorigenesis. The comparable TMB and lower VAF of EGFR mutations in early-stage disease suggest that innate resistance to EGFR-TKIs may be driven by concurrent GAs, supporting the consideration of combination therapies even in early-stage EGFR-mutant NSCLC.

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Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2026;58(1):107-114. Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

Citations

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Comparison of the safety and efficacy of remimazolam for sedation during bronchoscopy: a meta-analysis of randomized controlled trials
Yupei Yuan, Chunlei Chang, Jing Zhang, Liang Liang
PeerJ.2026; 14: e20552. CrossRef

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2 Web of Science
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