ESTRO 2025 - Abstract Book

S4012

Radiobiology - Tumour radiobiology

ESTRO 2025

The model also exhibited the ability to incorporate tumour microenvironment characteristics and realistically simulate response to radiotherapy under varying conditions.

Conclusion: The developed generalizable mathematical model allows for incorporation of tumour perfusion and oxygenation into radiobiological modelling.

Keywords: microenvironment, perfusion, oxygenation

References: [1] Mpekris F, Angeli S, Pirentis AP, Stylianopoulos T., "Stress-mediated progression of solid tumors: effect of mechanical stress on tissue oxygenation, cancer cell proliferation, and drug delivery.," Biomechanics and modeling in mechanobiology, 14, pp. 1391-1402, 2015. [2] Barker Jr JL, Garden AS, Ang KK, O'Daniel JC, Wang H, Court LE, Morrison WH, Rosenthal DI, Chao KC, Tucker SL, Mohan R., "Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system.," International Journal of Radiation Oncology* Biology* Physics, 59(4), pp. 960-970, 2004.

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Proffered Paper Epithelioids as a tool to evaluate the evolution of somatic mutations and response to radiotherapy in head and neck cancer patients Inês Ferreira 1,2 , Jose Valverde-Lopez 1 , Jakub Pęczek 1 , Kasandra Malasi 1 , Amy Bates 3 , John Tadross 3 , Glenn Harden 3 , Malcolm Cameron 3 , Chang-Bon Man 3 , Phoebe Roche 3 , Will Ince 3 , Andrew Lawson 4 , Adrian Baez Ortega 4 , Moritz Przybilla 4 , Richard Butler 1 , Rajesh Jena 3,5 , Marc de La Roche 6 , Iñigo Martincorena 4 , Gillian C Barnett 3,5 , David Fernandez Antoran 1,2,7 1 The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom. 2 Department of Pathology, University of Cambridge, Cambridge, United Kingdom. 3 Cambridge University Hospitals NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 4 Wellcome Sanger Institute, Wellcome Sanger Institute, Hinxton, United Kingdom. 5 Department of Oncology, University of Cambridge, Cambridge, United Kingdom. 6 Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. 7 Fundación ARAID, Instituto de Investigación Sanitaria Aragón (IIS ARAGÓN), Fundación ARAID, Instituto de Investigación Sanitaria Aragón (IIS ARAGÓN), Zaragoza, Spain Purpose/Objective: Despite the efficacy of radiotherapy (RT) in the management of head and neck squamous cell carcinoma (HNSCC), loco-regional recurrence (LRR) occurs in 15 to 50% of cases, representing a pivotal factor contributing to cancer related mortality [1]. Furthermore, radiation-induced injury to the salivary glands, which culminates in xerostomia, significantly worsens patients’ quality of life [2]. The objective of this study is to characterise epithelioids [3], a novel, long-term and passage-free in vitro 3D model, derived from patient biopsies. Epithelioids will be used to identify key genetic factors that influence LRR by monitoring the evolution of somatic mutations during RT, and to identify RT modalities that can preserve glandular function. Material/Methods: Tumours and a segment of surrounding healthy tissue were harvested from various head and neck subsites (n=12) from primary and recurrent HNSCC patients undergoing surgical resection or diagnostics biopsy at Cambridge University Hospitals NHS Foundation Trust as part of the Hamlet.rt Collect study (Cambridge, UK). Submandibular gland biopsies (n=3) were collected from patients undergoing neck dissection for radiological evidence of nodal metastasis. Epithelioids were established and maintained individually as described previously [3]. Cancer