ESTRO 2025 - Abstract Book

S3982

Radiobiology - Tumour radiobiology

ESTRO 2025

Immunohistochemistry staining of p16, p53, and Ki67 showed comparable distribution in PDOs, xenografts, and patient tumor material. DNA sequencing data showed typical tumor mutations in the PIK3CA, CDKN1B, ERBB2, RAF1 and PDGFRB genes. The organoid lines PMU 995 (p<0.0001) and PMU 1229 (p<0.001) showed a significant viability reduction after irradiation, in contrast to more resistant lines PMU 363 and PMU 616. Our screening assumed a radiosensitizing effect through ATM, PARP or EGFR/HER2 inhibition. Further investigations revealed an enhanced response to irradiation with a combined treatment of AZD0156, afatinib, and alpelisib, particularly in PMU 616 and 363. In contrast, PMU 995 and 1229 already exhibited significantly reduced viability in response to irradiation alone. Conclusion: To the best of our knowledge, we demonstrated for the first time the successful establishment and cultivation of patient-derived anal carcinoma organoids. This offers a new possibility in radiobiological research in this rare tumor entity and forms the basis for further translational studies. References: [1] Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, Peiffert D, Cervantes A, Arnold D. Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25 Suppl 3:iii10-20. [2] Driehuis E, Kretzschmar K, Clevers H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat Protoc. 2020 Oct;15(10):3380-3409. [3] Naumann M, Czempiel T, Lößner AJ, Pape K, Beyreuther E, Löck S, Drukewitz S, Hennig A, von Neubeck C, Klink B, Krause M, William D, Stange DE, Bütof R, Dietrich A. Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids. Cancers (Basel). 2022 Aug 3;14(15):3781. Digital Poster 3D printing-enhanced minibeam radiation therapy for targeted treatment of triple-negative breast cancer Zengyi Fang, Jinyi Lang, Meihua Chen Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, China Purpose/Objective: The integration of 3D printing technology into radiotherapy represents a significant advancement, offering new opportunities for patient-specific treatment solutions. This study explores the potential impact of 3D-printed devices, particularly within the context of minibeam radiation therapy (MBRT). Material/Methods: Custom 3D-printed collimators for MBRT were developed and their dosimetric properties evaluated using an X-RAD 320 irradiator. Subcutaneous triple-negative breast cancer (TNBC) models were treated with MBRT or conventional radiation therapy (CRT). Tumor tissues were analyzed histologically for relevant markers, and vascular changes and tumor perfusion were assessed using contrast-enhanced ultrasound and electron microscopy. Results: The 3D-printed collimators produced precise dose distributions, consistent with design specifications. MBRT significantly delayed tumor growth compared to CRT, despite similar valley doses. Histological analysis identified three distinct tumor habitats: proliferative, hypoxic, and necrotic regions. MBRT reduced vascular density and cellular proliferation, induced hypoxia, and promoted necrosis. Furthermore, MBRT induced a transient phase of vascular normalization, enhancing perfusion and endothelial integrity before reverting to a hypoxic state. This dynamic vascular response created an optimal therapeutic window for improved treatment efficacy. Keywords: anal cancer, patient derived organoids 1717