Importance of driver mutation assessment and driver-targeted therapy for early-stage NSCLC patients with non-R0 resection

Published: 20 June 2024| Version 1 | DOI: 10.17632/v4jxnb9gt3.1
Jeng-Sen Tseng


This data includes the raw data of EGFR genotyping by MassARRAY MALDI-TOF nucleotide mass spectrometry platform (Agena Bioscience, San Diego, CA) in the recent study. Abstract Objective: Non-small cell lung cancer patients with incomplete resection have a worse outcome. We aim to identify the risk factors for disease progression and death. Methods: Between August 2011 and December 2020, early-stage NSCLC patients who underwent operation but had a non-R0 resection were included. We analyzed their clinicopathological features and driver mutation status. Results: A total of 65 patients were included for analysis. The median follow-up time was 36.2 months. Thirty-nine patients (60.0%) had experienced disease progression and 3 patients (4.6%) died. Twenty-two patients (33.8%) harbored driver mutation. In multivariate analysis, the presence of driver mutation predicted a higher risk of progression (adjusted OR 24.08 [95% CI 2.77-209.01], P = 0.004). ECOG PS 2 (adjusted HR 3.49 [95% CI 1.10-11.03], P = 0.033), higher tumor stage (adjusted HR 2.55 [95% CI 1.06-6.17], P = 0.037), and the presence of driver mutation (adjusted HR 3.28 [95% CI 1.55-6.94], P = 0.002) all predicted a shorter progression-free survival (PFS). Driver-targeted therapy was associated with a longer post-progression survival when patients were documented to have disease progression (adjusted HR 0.38 [95% CI 0.16-0.91], P = 0.030). There was no significant impact of driver mutation status on overall survival. Conclusions: Although the presence of driver mutation was associated with a higher risk of disease progression and a shorter PFS, patients with disease progression can benefit from driver-targeted therapy, which led to a similar overall survival with that of driver negative or unknown population; hence, comprehensive and earlier analyses of driver mutation are recommended.


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EGFR mutations were tested using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has been validated as one of standard method to detect these drive mutations in our previous studies and has been implemented in Taiwan clinical practice (1-5). Briefly, genomic DNA (gDNA) was extracted for serial biochemical reactions, including 40 cycles PCR reaction, SAP (shrimp alkaline phosphatase) treatment, and 200 cycles single nucleotide extension reaction. After resin clean up, samples were loaded onto the matrix of SpectroCHIP by Nanodispenser then analyzed by Bruker Autoflex MALDI-TOF MS. Data were collected and analyzed by Typer4 software (Agena Bioscience, San Diego, CA). Primers for PCR and probes for single nucleotide extension were specifically designed according to corresponding driver mutations. All the aforementioned methods for driver mutation detection have been included in the written informed consent approved by the Institutional Review Board of Taichung Veterans General Hospital. References 1. Ou WF, Liao PY, Hsu YW, et al.: Outcome of Thromboembolic Events and Its Influence on Survival Time of Advanced NSCLC Patients Treated with Antiangiogenic Therapy. Cancer Manag Res 15: 1251-1262, 2023. 2. Hsu KH, Ho CC, Hsia TC, et al.: Identification of five driver gene mutations in patients with treatment-naive lung adenocarcinoma in Taiwan. PLoS One 10: e0120852, 2015. 3. Su KY, Kao JT, Ho BC, et al.: Implementation and Quality Control of Lung Cancer EGFR Genetic Testing by MALDI-TOF Mass Spectrometry in Taiwan Clinical Practice. Sci Rep 6: 30944, 2016. 4. Su KY, Chen HY, Li KC, et al.: Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol 30: 433-440, 2012. 5. Tseng JS, Yang TY, Tsai CR, et al.: Dynamic plasma EGFR mutation status as a predictor of EGFR-TKI efficacy in patients with EGFR-mutant lung adenocarcinoma. J Thorac Oncol 10: 603-610, 2015.


Clinical Genetics, Mass Spectrometry, Gene Mutation, Lung Cancer, Targeted Therapy, Molecular Diagnostics