Ultrasensitive ctDNA monitoring reveals early predictors of immunotherapy response in advanced cancer.

ABSTRACT: Circulating tumor DNA (ctDNA)-based response assessment is appealing but limited by conventional analytical thresholds. We utilized a whole genome sequencing based, tumor-informed ultrasensitive ctDNA assay which tracked ~1800 somatic mutations to analyze 227 longitudinal plasma samples from 39 patients with advanced/metastatic cancers receiving immune checkpoint inhibitors (ICIs). ctDNA was detected from 2.0-239,315 PPM (median limit of detection: 1.77 PPM), with 33% of positive detections below 100 PPM. Early molecular response, defined as >50% ctDNA reduction or sustained ctDNA negativity from baseline to first follow-up, strongly predicted improved progression-free survival (PFS) (hazard ratio (HR) = 0.09, 95% CI: 0.02-0.39, p = 0.001) and was independently prognostic of PFS. Molecular

SUBMITTER: Nishizaki D 

PROVIDER: S-EPMC12936199 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature