Non-invasive radiogenomic mapping of the SMARCAL1-driven ferroptotic niche is associated with longitudinal MRD-negative surveillance in early-stage NSCLC

BackgroundPost-operative molecular residual disease (MRD) detection using circulating tumor DNA (ctDNA) has been established as a sensitive biomarker for early recurrence risk stratification in early-stage non-small cell lung cancer (NSCLC). However, the biological heterogeneity of patients MRD-negative at baseline remains incompletely characterized, and a proportion subsequently experience MRD conversion and radiographic recurrence.

We investigated whether pre-operative radiomic features could non-invasively capture the spatial organization of a ferroptosis-enriched, immune-active tumor microenvironment associated with sustained post-operative MRD negativity.MethodsIn this single-center translational cohort nested within the prospective CTONG 2201 trial (NCT05457049), 71 patients with completely resected stage IB–IIIA NSCLC, MRD-negative at two post-operative landmarks, were followed under dynamic observation without immediate adjuvant therapy. A Rad-Score was derived from 1,432 pre-operative contrast-enhanced CT radiomic features using a pre-specified five-layer pipeline.

Whole-exome sequencing, bulk RNA-seq with CIBERSORTx, and 10x Visium spatial transcriptomics in 14 tumors (five High, four Intermediate, five Low Rad-Score; 36,318 quality-controlled spatial spots) characterized molecular correlates.