Clinical validity of ultrasensitive single-digit parts per million ctDNA detection in non–small cell lung cancer.

8017 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for detecting molecular residual disease (MRD) and predicting recurrence after curative treatment in non-small cell lung cancer (NSCLC). Ultrasensitive personalized assays have demonstrated clinical validity at detection thresholds of ~80-100 parts per million (PPM). As this assay can detect ctDNA at concentrations an order of magnitude lower (below 10 PPM), we extend these analyses to explore the clinical outcomes of patients with single-digit PPM ctDNA. In the future, this may guide adjuvant treatment decision-making. Methods: We analyzed longitudinal plasma samples from 431 patients with stage IA–IIIB NSCLC enrolled in the TRACERx study and treated with upfront surgery. We achieved ultrasensitive MRD testing with ctDNA limits of detection as low as 1-3 PPM across 2994 plasma samples using NeXT Personal, a personalized liquid biopsy assay which tracks up to ~1,800 patient-specific somatic variants. Plasma samples were classified as preoperative, postoperative landmark (10–120 days), or longitudinal follow-up. Associations with recurrence-free survival (RFS) and overall survival (OS) were assessed. Results: Preoperative ctDNA detection below 10 PPM was associated with inferior recurrence-free survival (RFS) and overall survival (OS) compared to undetectable ctDNA in individuals with lung adenocarcinoma (