Here, we assessed whether longitudinal mutant ctDNA monitoring using blood and saliva samples could reflect response and resistance to osimertinib, a third-generation EGFR-TKI, and tumor burden measured by three-dimensional volumetric computed tomography (CT) in the setting of a prospective clinical trial of local ablative therapy (LAT) for oligoprogressive, and EGFR-mutant NSCLC upon treatment with osimertinib. Here, EGFR is linked to non-small cell lung carcinoma.