Whole-genome liquid biopsy predicts early lung cancer recurrence

A patient-specific whole-genome liquid biopsy detected circulating tumor DNA (ctDNA) in patients with stage IA lung adenocarcinoma and identified molecular evidence associated with recurrence months before tumors appeared on imaging, according to a peer-reviewed experimental study in The Journal of Molecular Diagnostics. The study examined serial blood samples collected during follow-up after treatment, using tumor-specific DNA patterns to estimate relapse risk in people with very early-stage non–small-cell lung cancer.

To establish the test’s patient-specific signature, researchers compared DNA from a surgical pathology sample with DNA from a buffy-coat sample. Both sets underwent whole-genome sequencing (WGS) to generate a mutational pattern associated with the patient’s tumor. At follow-up visits, investigators extracted cell-free DNA from plasma, performed WGS and analyzed it using the patient-derived signature together with an artificial-intelligence pattern-recognition algorithm. The reported result was that positive ctDNA findings were highly sensitive markers of minimal residual disease, while negative results were strongly correlated with sustained remission in the study population.

The work was led by Matija Snuderl, MD, of NYU Langone Health and the Laura and Isaac Perlmutter Cancer Center, with co-lead investigator Harvey I. Pass, MD, of NYU Langone Health. Asaf Zviran, PhD, of C2i Genomics developed the WGS liquid-biopsy technology. The investigators said that serial monitoring across treatment stages could provide information about relapse before standard imaging detected a physical tumor. The release describes the work as an experimental study and identifies the journal article as “Predicting Recurrence of Stage IA Lung Adenocarcinoma Using Circulating Tumor Cell-Free DNA Whole-Genome Mutational Signatures.”

Patients with stage I–II non–small-cell lung cancer are usually treated with surgery, and the source reports that recurrence rates in stage I disease range from 5% to 19%. Imaging remains the standard form of follow-up after surgery or initial therapy. The study’s finding is that a blood-based molecular signal was associated with recurrence in the earliest clinical stage, at a time when the disease was not yet apparent on scans. The authors present this earlier signal as a potential basis for risk-adapted surveillance and personalized post-treatment care, but the reported study does not demonstrate that changing treatment on the basis of test results improves survival or prevents recurrence.

The source does not provide the number of participants, the timing distribution of blood collections, or numerical sensitivity, specificity or lead-time estimates. Its findings therefore support the conclusion that, in the experimental cohort, serial WGS analysis of ctDNA patterns was associated with relapse before imaging showed tumors and that negative results were associated with sustained remission. The publication’s focus on stage IA lung adenocarcinoma also limits the direct scope of the reported finding: the release describes monitoring across treatment stages, but does not establish the same performance for all stages or all forms of lung cancer.

Subject of Research: Experimental ctDNA whole-genome liquid biopsy for recurrence prediction in stage IA lung adenocarcinoma

Article Title: Novel blood test detects lung cancer traces long before scans

Article References: Novel blood test detects lung cancer traces long before scans. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: lung adenocarcinoma, liquid biopsy, circulating tumor DNA, cancer recurrence, whole-genome sequencing, minimal residual disease, molecular monitoring, early-stage lung cancer, artificial intelligence, Novel, blood, test