Non-invasive radiogenomic mapping of the SMARCAL1-driven ferroptotic niche is associated with longitudinal MRD-negative surveillance in early-stage NSCLC.
High pre-operative Rad-Score is associated with longer MFS after non-small cell lung cancer resection
Non-invasive radiogenomic mapping of the SMARCAL1-driven ferroptotic niche is associated with longitudinal MRD-negative surveillance in early-stage NSCLC.
Post-operative molecular residual disease (molecular residual disease) 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 (non-small cell lung cancer).
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 molecular residual disease negativity.
In this single-center translational cohort nested within the prospective CTONG 2201 trial (NCT05457049), 71 patients with completely resected stage IB-IIIA non-small cell lung cancer, molecular residual disease-negative at two post-operative landmarks, were followed under dynamic observation without immediate adjuvant therapy.
Higher radiomic score linked to lower hazard of disease events, favoring sustained molecular residual disease negativity.
Nine stability-validated radiomic features (selection frequency Π ≥ 0.60, all; ≥ 0.80 for 7/9) constituted the Rad-Score.
High Rad-Score tumors exhibited elevated TMB ( P < 0.001, BH-FDR q < 0.001) and APOBEC signatures (SBS2, SBS13: q < 0.001; SBS4 non-significant after FDR), enriched CD8 + T cells and M1 macrophages (q < 0.01), and contiguous ferroptotic niches with monotonically increasing activity across the Rad-Score continuum (Spearman ρ = 0.87).
In this externally validated, functionally interrogated translational cohort, a pre-operative CT-derived Rad-Score is associated with sustained molecular residual disease-negative surveillance, provides a non-invasive surrogate for a SMARCAL1-driven ferroptotic-immune niche, and requires prospective validation Non-small cell lung cancer; Molecular residual disease; Radiogenomics; Spatial transcriptomics; Ferroptosis; SMARCAL1; CXCL9/10-CXCR3 axis.
CLINICAL