Brief Report: Discordance Between Liquid and Tissue Biopsy-Based Next-Generation Sequencing in Lung Adenocarcinoma at Disease Progression

Abstract

Introduction: High concordance rates between NGS performed on circulating tumor DNA (“liquid biopsy”) and tissue DNA are observed at the time of lung adenocarcinoma diagnosis. Concordance at disease progression, especially through targeted therapy, remains unknown.Methods: We retrospectively evaluated patients with lung adenocarcinoma who received paired Guardant360 and tissue-based NGS at diagnosis and/or progression. Clinically informative concordance was defined as both modalities generating results leading to the same clinical action. Clinically informative discordance was defined as one modality identifying a clinically informative result that the other did not. Clinically non-informative concordance was defined as both tests identifying a clinically unactionable mutation.Results: 138 paired tests were assessed among 126 patients. Among paired tests with at least one clinically informative result (n=123), concordance rate at diagnosis was 79.4%(n=50/63), compared to 40.0%(n= 24/60) at disease progression (p<0.001). Among 49 clinically informative discordant paired tests, actionable mutations were identified on tissue-based NGS alone in 34 instances (69.4%) compared to 13(26.5%) on liquid biopsy.Conclusions: We demonstrate a steep decline in tissue-liquid biopsy concordance from diagnosis to disease progression. Utilizing both liquid and tissue NGS strategies at progression may help overcome this limitation.