Ultra-Sensitive ctDNA Assay Predicts Treatment Response 65 Days Before Imaging in Esophagogastric Cancer
Using the NeXT Personal tumour-informed liquid biopsy platform in a phase II trial of 24 metastatic esophagogastric cancer patients, researchers found that ctDNA dynamics strongly correlated with tumour size changes. Lack of early molecular response was associated with significantly worse overall and progression-free survival. Molecular progression preceded imaging-detected progression by a median of 65 days, suggesting ultra-sensitive ctDNA monitoring could meaningfully accelerate treatment decisions.
The original study
Monitoring treatment response using an ultra-sensitive ctDNA assay in advanced esophagogastric cancer patients.
- Authors
- Nixon AB, Navarro FCP, Zhou KI, Abbott CW, McDaniel L, Ravi N, et al.
- Journal
- Scientific reports
- PMID
- 41872254
Original abstract
To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables earlier prediction of treatment response and detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. A total of 24 patients were evaluated, and all were ctDNA-positive at baseline. ctDNA levels varied from 406,067 down to 1.5 parts per million (PPM) with a median limit of detection of 2.03 PPM. ctDNA dynamics were highly correlated with changes in tumor size (ρ = 0.59, p = 7.3 × 10- 9). Lack of early molecular response (50% or greater decrease in ctDNA levels at first available time point after 30 days, C2D1 or C4D1) was associated with worse overall survival (OS) (HR 4.5, 95% CI 1.2-16.7, p = 0.02) and progression-free survival (PFS) (HR 10.4, 95% CI 2.2-49.8, p = 0.003). Lack of molecular clearance of ctDNA was associated with worse OS (HR 7.1, 95% CI 1.6-31.7, p = 0.01) and PFS (HR 19.9, 95% CI 2.5-158.2, p = 0.005). Molecular progression (ctDNA increase) preceded imaging-derived progression by a median lead time of 65 days. These results suggest that ultra-sensitive liquid biopsy approaches could improve treatment decision-making for mEGC patients receiving chemotherapy and immunotherapy.