S2639
Radiobiology - Tumour radiobiology
ESTRO 2026
comprising of 100 genes that effectively discriminated between poor and good radiation responders (Figure 2A, r=0.81, p=1.2x10-6). Permutation testing and bootstrap validation confirmed robust performance of this score (Figure 2B). Identified gene-sets were enriched for co-expressed gene modules associated with metabolism, signal transduction and cell migration (Figure 2C).
developing targeted radiosensitisers and biomarkers to guide radiotherapy use. However, OAC is characterised by substantial inter-patient heterogeneity, which limits the applicability of analyses focussed on conventional 2D models that fail to mirror population-level diversity. We reasoned that a patient-derived organoid (PDO) biobank would more faithfully recapitulate heterogeneity and allow for sensitive between-patient comparisons that would enable the identification of drivers of treatment response. Material/Methods: We derived 25 OAC PDOs that were confirmed through 30X (PDO) and 50X (parent tissue) whole genome and bulk-RNA sequencing to capture the driver gene, mutational signature and patient-specific gene expression patterns of their parent tissue. Each was subjected to a single fraction of 0-8Gy irradiation one day after seeding and relative organoid formation efficiency (OFE) determined by assessing organoid formation at 10 days across radiation dose levels. Relative OFE was compared with parent tissue clinicopathological features, and OFE association with baseline genomic and transcriptomic profiles assessed using Spearman correlation analysis (r). Correlation analyses were validated by permutation and bootstrap resampling followed by gene set enrichment. Results: A diversity of radiation responses were captured, reflected by integral OFE values of 0.44 to 0.98. These did not correlate with donor clinicopathological or treatment characteristics (Figure 1).
Figure 2 Conclusion:
OAC radiation sensitivity does not correlate with baseline genomic features but can be predicted by a transcriptomic signature developed using a PDO biobank that recapitulates population-level tumour diversity. References: 1 Hoeppner J, Brunner T, Schmoor C et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med 2025;392:323-335. Keywords: Oesophageal adenocarcinoma, transcriptome ALDH3A1 influences radiosensitivity in head and neck squamous cell carcinoma by attenuating the cGAS-STING response via regulation of autophagy Xiufang Qiu, Zhaodong Fei Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China Purpose/Objective: To investigate the impact of ALDH3A1 on the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) and its underlying mechanism, and to ascertain the feasibility of targeting ALDH3A1- Proffered Paper 4428
Figure 1There was no significant or substantial correlation between OFE and baseline genomic features including tumour mutational burden (r=-0.19, p=0.36), whole genome instability (r=-0.13, p=0.53), HRD status (r=0.01, p=0.96) and ploidy (r=-0.03, p=0.90). Radiation sensitivity did not correlate with OAC driver gene status or specific DNA damage response gene mutations. Only 16 genes significantly differed in expression between the most (OFE 0.70- 0.98) and least (OFE 0.44-0.56) radiation sensitive PDOs. We therefore studied the impact of gene expression networks and identified a signature
Made with FlippingBook - Share PDF online