Novel Whole Genome Sequencing Assay Demonstrates Promise in Detecting Ultrasensitive MRD Among Patients With Early-Stage Non-Small Cell Lung Cancer
Study results demonstrated that the use of a novel whole genome sequencing (WGS) tumor-informed assay (Foresight CLARITY) provided greater ultrasensitive molecular residual disease (MRD) detection compared to historical controls with a first-generation assay (ctDNA Lung DETECT) among patients with early-stage non-small cell lung cancer (NSCLC).
These data were first presented by Filippo de Marinis, MD, Fred Hutchinson Cancer Center, Seattle, Washington, at the 2025 IASLC World Conference on Lung Cancer in Barcelona, Spain.
In this study, researchers collected 140 blood and tissue samples from 30 patients with stage I NSCLC at 3 time points: preoperatively, 3 to 6 weeks postoperatively, and 1 year postoperatively. Tissue samples were turned into formalin-fixed paraffin-embedded tissue samples and underwent WGS to identify 5000 somatic variants and create Bespoke panels and blood plasma samples underwent MRD testing.
At analysis, ctDNA was detected in 67.9% of preoperative samples and 37.9% of postoperative samples. The preoperative ctDNA detection rate was 33% in patients with stage IA disease and 71% in patients with stage IB disease. Landmark MRD was detectable in 55% of patients who experienced disease relapse. Preoperative and postoperative detection of MRD was associated with shortened recurrence-free survival (RFS) and 1-year MRD detection was associated with RFS (hazard ratio [HR] 10.7; 95% confidence interval [CI] 2.4 to 48; P = .0001). Median time to recurrence was 10 months among patients who experienced disease recurrence (37%) and MRD at landmark analysis (n = 6). In samples collected within 12 months of relapse (n = 14), 92.9% of samples had detectable MRD. MRD was observed in patients who received adjuvant therapy.
“Ultrasensitive MRD detection using a WGS tumor-informed assay demonstrated higher rates of MRD detection in clinical stage I patients than prior reports using a first-generation assay,” concluded Dr de Marinis. “These results support exploring ultrasensitive ctDNA MRD-guided treatment strategies in stage I NSCLC.”
Source:
Baik C, de Marinis F, Bonanno L, et al. Ultrasensitive MRD improves detection in resectable stage I NSCLC. Presented at the 2025 IASLC World Conference on Lung Cancer. September 6-9, 2025. Barcelona, Spain. Abstract MA03.01
