Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma in the TRACERx study

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, ctDNA was preoperatively detected within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM stage 1 disease. ctDNA predicted worse clinical outcome, and patients with LUAD with < 80 ppm preoperative ctDNA levels experienced reduced overall survival compared with ctDNA-negative LUAD patients. The authors conclude that, although prospective studies are needed to confirm the clinical utility of the assay, these data show that this approach has the potential to improve disease stratification in early-stage LUADs.