ESTRO 2025 - Abstract Book

S4029

Radiobiology - Tumour radiobiology

ESTRO 2025

response and vascularisation genes at 30Gy. All three radioresistant 30Gy irradiated PDOs remained viable and demonstrated at least one phenotypic characteristic of radioresistance compared with the unirradiated control (Fig.2).

To explore the molecular contributors to this we isolated eight single clones from a single bulk radioresistant PDO. These demonstrated remarkable variability in OFE, which correlated with phylogenetic profiles inferred from WGS data, as well as enrichment of transcriptomic programmes relating to cellular metabolism (Fig.2). Transcriptomic and epigenomic heterogeneity were also observed, and were linked with amplification of chromosome 7. Conclusion: Radioresistant OAC PDOs are characterised by a dose-dependent increase in SNV and indel burden, substantially altered methylation profiles and dose-dependent transcriptional changes. This masks considerable persistent phenotypic and related molecular heterogeneity, suggesting a role for clonal competition and cooperation in dictating response to high doses of fractionated radiation.

Keywords: Oesophageal adenocarcinoma; Genomics; Evolution

References: 1 Deboever N et al. Advances in diagnosis and management of cancer of the esophagus. BMJ 2024;385:e074962.

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Digital Poster Modulation of radiation-induced bystander effects by microbeam radiation therapy in murine glioblastoma Narayani Subramanian 1,2 , Mariaelvy Bianchini 1,2 , Stephanie E Combs 1,2 , Susanne Raulefs 1,2 , Thomas E Schmid 1,2 , Stefan Bartzsch 1,2 1 Department of Radiation Oncology, School of Medicine and Health, TUM University Hospital, Technical University of Munich, Munich, Germany. 2 Institute of Radiation Medicine, Helmholtz Centre, Munich, Germany Purpose/Objective: Microbeam radiation therapy (MRT) is a novel still pre-clinical form of radiotherapy consisting of 25–100 μm wide arrays of X-ray microbeams. This distribution leads to high peak-dose irradiated regions and low valley-dose irradiated regions in the target. This peak to valley dose ratio (PVDR) of MRT has been shown to substantially lower normal tissue damages while simultaneously maintaining or even increasing local tumor control compared to conventional radiotherapy (CRT) [1,2]. The underlying mechanisms of MRT are not yet fully understood; among these are non-targeted effects, which primarily consist of radiation-induced bystander effects (RIBE). It is hypothesized that peak-irradiated cells lead to a damage response in their neighbouring valley-irradiated cells either via gap junction signalling or through secreted factors. The mediators of RIBE are not well characterized, but