Faculty, Staff and Student Publications

Language

English

Publication Date

8-4-2025

Journal

Cancer Discovery

DOI

10.1158/2159-8290.CD-24-1704

PMID

40299851

PMCID

PMC12324966

PubMedCentral® Posted Date

2-4-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. Circulating tumor DNA (ctDNA) minimal residual disease after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. Here, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration is prognostic for disease progression and integrate additional pre-CRT risk factors including radiomics into a combined model that improves outcome prediction. Our results suggest that tumor features, radiomics, and mid-CRT ctDNA analysis are complementary and can identify patients at high and low risk of progression to potentially enable response-adapted therapies.

Keywords

Humans, Lung Neoplasms, Circulating Tumor DNA, Female, Male, Carcinoma, Non-Small-Cell Lung, Middle Aged, Risk Assessment, Prognosis, Biomarkers, Tumor, Aged, Chemoradiotherapy, Liquid Biopsy, Radiomics

Published Open-Access

yes

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