Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence in patients with early-stage non-small cell lung cancer (NSCLC). Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. In a recent study, researchers analyzed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating Tumour DNA (LUCID) study, with disease stage I (49%), II (28%), and III (23%); 62% were adenocarcinomas. ctDNA was detected in 26% of samples, at median MAF of 0.047%, and prior to treatment in 87%, 77%, and 24% for disease stage III, II, and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse. All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all eight patients that relapsed within 300 days of treatment.


Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.