Real-world plasma-based next-generation sequencing findings in metastatic lung adenocarcinoma: a single-center retrospective study

Objective: To determine the frequency and distribution of genomic alterations detected by plasma-based next-generation sequencing(NGS) in metastatic lung adenocarcinoma in a real-world setting.Patients and Methods: This retrospective single-center study included 76 patients with histologically confirmed metastatic lungadenocarcinoma who underwent plasma circulating tumor DNA (ctDNA) NGS between March 2021 and July 2024. Targetedsequencing was performed using a 28-gene panel. Genomic alterations were classified as actionable according to current clinicalguidelines. Concordance with available tissue-based molecular testing was evaluated in the internal cohort.Results: At least one genomic alteration was detected in 43/76 patients (56.6%). Among NGS-positive patients, 19/43 (44.2%) had ≥2alterations. Actionable alterations were identified in 24/76 patients (31.6%;55.8% of NGS-positive cases). The most frequently alteredgenes were TP53 (35.5%), EGFR (18.4%), and KRAS (13.2%). In an exploratory survival analysis of internal NGS-positive patients(n=19), median overall survival (OS) was 27 vs 29 months for patients with and without actionable alterations, respectively (p=0.94).Conclusion: Plasma-based NGS identifies clinically relevant genomic alterations in metastatic lung adenocarcinoma and complementstissue-based molecular testing in routine practice.