Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study

Introduction: Molecular residual disease detected circulating tumor DNA (ctDNA) has been reported to predictive of patients' outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detection with long-term follow-up in lung cancer needed. Here, we report on a cohort of patients with NSCLC who underwent definitive surgery and ctDNA analysis in pre-operative, adjuvant, and surveillance settings. Method: Plasma samples were collected from 46 patients clinical stage II-III NSCLC before surgery (n = 46), after surgery (n = 45), and every six months until two years thereafter 78). A clinically validated, personalized, tumor-informed plex polymerase chain reaction-next-generation sequencing assay was used for the detection and quantification of ctDNA retrospectively analyzed plasma samples. Results: Circulating tumor DNA was detected in the postoperative (within 51 days after surgery) plasma samples in 13% (6/45) of patients (landmark analysis). of them had disease recurrence within a median of months. These patients had shorter recurrence-free overall survivals than those without detectable ctDNA landmark time point (p < 0.01) and in multivariate lyses (p < 0.03). Longitudinally (considering all operative follow-up time points), ctDNA was detected 13 patients, all of whom experienced disease recurrence (positive predictive value = 100%). Three patients who had central nervous system-only metastases did not have detectable ctDNA. Conclusions: The presence of ctDNA post-surgery or during surveillance identifies patients with NSCLC at high risk recurrence. Serial testing is important to detect disease recurrence earlier (lead-time: 3.2 months).