S794
Clinical - Lung
ESTRO 2026
comprising 17 with CAEs (10 grade ≥ 3) and 33 without CAEs, including 16 controls without CAE or radiation pneumonitis. Samples were collected at baseline, near the end of CRT, or at the first follow up visit. Sequencing libraries were prepared from 10ng bisulfite-converted cfDNA. Reads were trimmed with Trim Galore, aligned to GRCh38 using Bismark/Bowtie2, and methylation calls were extracted from cytosine reports. cfDNA tissue origins were inferred by methylome deconvolution using UXM3. Wilcoxon signed-rank tests compared cfDNA proportions and methylation levels between pre- and post-CRT samples. ReactomePA R package was used to identify enriched pathways. Spearman correlation was used to assess associations between methylation levels and cardiac biomarkers NT-proBNP and hs-cTnT in differentially methylated regions (DMRs). Results: WGBS revealed cfDNA enrichment from cardiomyocytes, heart fibroblasts, and endothelial cells after CRT. Endothelial-derived cfDNA increased significantly during CRT and declined thereafter (p<0.01), indicating vascular injury as an early response to CRT. Cardiomyocyte-derived cfDNA increased in patients receiving mean heart dose >15Gy (p=0.04) and in those with any grade of CAEs (p=0.09), but showed no change with ≤ 15Gy (p=0.96) or without CAE (p=0.97). Heart fibroblast-derived cfDNA did not change significantly at follow-up in CAE patients (p=0.3) but decreased in those without CAE (p=0.04). To elucidate CRT-induced cardiac injury, CpG-binned methylation profiles were compared between pre- and post-CRT plasma samples from 10 patients with grade ≥ 3 CAEs and 16 controls. Significant DMRs (200 bp bins) with p ≤ 0.01 and absolute paired mean difference >20% only in CAE patients were identified, involving genes related to neurohumoral signaling, mitochondrial energetics, ECM/fibrosis, and angiogenesis. Reactome pathway analysis further implicated pathways related to cardiac injury, including coagulation, inflammation and immune recruitment, cardiomyopathy, and endocrine modulation. Of note, methylation in a hypermethylated promoter region on chromosome 8 (MIR124-2HG), associated with cardiac angiogenesis and dysfunction, was positively correlated with hs- cTnT ( ρ =0.40, p=0.01) and NT-proBNP ( ρ =0.31, p=0.04).
outcomes. The model demonstrated good discrimination (AUC = 0.82; 95% CI = 0.70-0.94) and internal stability, with 81 % sensitivity and 74 % specificity. Conclusion: The 3–6 month post-SBRT radiological pattern is a practical and clinically relevant prognostic indicator. When combined with simple clinical and dosimetric parameters, it supports earlier indentification of patients at higher LR/LRR risk. Due to the limited sample size and low number of events, further studies are needed to validate these findings. References: 1- Coroller TP, Agrafiotis DK, Huynh E, et al. Radiomic- based pathological response prediction from pre- and post-treatment CT images in lung cancer patients undergoing SBRT. Radiother Oncol. 2017;122(3):420– 426.2- Lucia F, Boldrini L, Chiloiro G, et al. CT-based radiomics for prediction of local control in early-stage NSCLC treated with SBRT. Phys Med. 2018;55:78–85.3- Zeng Y, Lin C, Lu Z, et al. Radiomics analysis of CT imaging for prediction of local recurrence after SBRT in lung cancer. Front Oncol. 2019;9:1234. Keywords: Pulmonary nodule, SBRT, radiological patterns Digital Poster 2579 circulating cell-free DNA as a predictive biomarker of cardiac adverse events in NSCLC patients treated with concurrent chemoradiotherapy Ting Xu 1 , Xin Hu 2 , Yue Lu 3 , Mei Chen 1 , Efstratios Koutroumpakis 4 , Jianjun Zhang 2 , Anita Deswal 4 , Marcos R Estecio 3 , Zhongxing Liao 1 1 Department of Radiation Oncology-Thoracic, The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Department of Head and Neck/Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 3 Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, USA. 4 Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, USA Purpose/Objective: cfDNA and its methylation patterns reflect therapy- induced epigenetic alterations1,2. This study evaluated cfDNA as a predictive biomarker for cardiac adverse events (CAEs) induced by chemoradiation therapy (CRT) in NSCLC patients and explored genes involved in cardiovascular injury using whole-genome bisulfite sequencing (WGBS). Material/Methods: WGBS was performed on plasma cfDNA using the NovaSeq X platform (Illumina) from 50 NSCLC patients,
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