ESTRO 2025 - Abstract Book

S4017

Radiobiology - Tumour radiobiology

ESTRO 2025

Conclusion: This study demonstrates that lower doses of MRT can achieve superior or equal TGD than higher doses of BB. Our results indicate towards possible broadening of therapeutic window for the treatment of lung cancers.

Keywords: spatial fractionation, therapeutic enhancement

References: 1. Schültke, Elisabeth et al. “Microbeam radiation therapy - grid therapy and beyond: a clinical perspective.” The British journal of radiology vol. 90,1078 (2017): 20170073. 2. Potez, Marine et al. “Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms.” International journal of radiation oncology, biology, physics vol. 105,5 (2019): 1126-1136.

3996

Proffered Paper The role of homologous recombination factors PSMC3IP and RAD54L as regulators of stemness and radioresistance in patients with HNSCC Jacqueline Nathansen 1 , Tim Schädlich 1,2 , Sandra Classen 3 , Kerstin Borgmann 3 , Dominik Haim 4,5 , Max Kemper 6,5 , Steffen Löck 1,2,7 , Mechthild Krause 2,1,7 , Anna Dubrovska 1,7,8 , Annett Linge 2,1,7 1 OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 2 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 3 Department of Radiotherapy & Radiation Oncology, Hubertus Wald Tumor Center-University Cancer Center Hamburg (UCCH), University Medical Center Hamburg Eppendorf, Hamburg, Germany. 4 Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 5 National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany. 6 Department of Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 7 German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 8 Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden, Germany Purpose/Objective: Patients with locally advanced (LA) HNSCC usually receive primary radiochemotherapy (RCT) or postoperative cisplatin-based radiochemotherapy (PORT-C). Human papillomavirus (HPV) status is a favorable prognostic factor, and personalized treatment options for high-risk patients with HPV-negative HNSCC are urgently warranted. Our study focuses on discovering the molecular mechanisms connecting HNSCC stemness driven by Oct4 and MYC transcription factors and homologous recombination (HR) factors PSMC3IP and RAD54L to develop new prognostic biomarkers and potential therapeutic strategies. Material/Methods: The role of Oct4, MYC, RAD54L, and PSMC3IP in the regulation of cellular radioresistance was analyzed by 2D and 3D radiobiological assays in several HPV-negative HNSCC cell lines. Genetic knockdown or knockout of gene expression was combined with PARP inhibition by olaparib and RT to analyze potential synthetic lethality effects. PCR array, cell cycle analysis, ChIP assay and other molecular methods were used to analyze the mechanisms connecting stem cell regulators Oct4 and Myc with HR machinery. The levels of protein expression were evaluated by immunohistochemical (IHC) analysis in tumor tissues from patients with LA HNSCC treated with PORT-C (n = 167) or primary RCT (n = 98). The protein levels were associated with loco-regional control (LRC) rates.