ESTRO 2020 Abstract Book

S319 ESTRO 2020

University of Freiburg, Freiburg, Germany ; 19 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Freiburg, Freiburg, Germany ; 20 Clinical Cooperation Unit Translational Radiation Oncology- Heidelberg Ion Therapy Center HIT- Department of Radiation Oncology, University of Heidelberg Medical School, Heidelberg, Germany ; 21 National Center for Tumor Diseases NCT, University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg, Germany ; 22 Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg, Germany ; 23 Department of Radiation Oncology, Ludwig- Maximilians-Universität, Munich, Germany ; 24 Clinical Cooperation Group, Personalized Radiotherapy in Head and Neck Cancer- Helmholtz Zentrum, Munich, Germany ; 25 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Munich, Munich, Germany ; 26 Department of Radiation Oncology, Technische Universität München, Munich, Germany ; 27 Department of Radiation Sciences DRS, Institut für Innovative Radiotherapie iRT- Helmholtz Zentrum Munich, Neuherberg, Germany ; 28 Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen- Eberhard Karls Universität Tübingen, Tübingen, Germany ; 29 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Tübingen, Tübingen, Germany ; 30 Tumour- and Normal Tissue Bank, University Cancer Centre UCC- University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 31 German Cancer Research Center, Deutsches Krebsforschungszentrum DKFZ, Heidelberg, Germany Purpose or Objective To personalize radiotherapy of locally advanced head and neck squamous cell carcinoma (HNSCC), gene signatures have been developed that are related to processes involved in radioresistance of HNSCC. To date, most of these signatures were developed for patients who have received primary radiotherapy (pRCTx). The aim of our study was (I) to apply existing gene signatures related to different radio-biological processes for patients treated with postoperative radiochemotherapy (PORT-C) and (II) to validate these signatures in xenograft models. Material and Methods This study is based on two cohorts: (i) 128 patients with locally advanced HVP16 DNA-negative HNSCC who received PORT-C in a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) between 2005 and 2011 and (ii) 60 mice bearing xenografts of 10 cell lines of human squamous cell carcinoma. Gene signatures related to cancer stem cell (CSC) markers [1], DNA repair [2], hypoxia [3], radiosensitivity [4] and epithelial mesenchymal transition (EMT) [5] were selected. Whole transcriptome analysis was performed using the HTA 2.0 Array (Affymetrix). Based on the gene signatures, risk groups were generated as described in the original publications (i) for the PORT-C cohort and (ii) for the xenograft data. The primary endpoint for the PORT-C cohort was loco-regional control (LRC), while the endpoint for the xenograft data was the dose to control 50% of the tumours (TCD50). The endpoints were evaluated byCox regression and the Mann-Whitney-U test, respectively. Results All signatures were able to stratify patients treated with PORT-C into risk groups with a significant difference in LRC (figure A) or showed a statistical trend (radiosensitivity

with a larger CTV HR volume and higher FIGO stage (III and IVA). This indicates that the local tumour extent significantly contributes to increased risk of ureter strictures and fistulas. The incidences reported in this analysis compare favourably with previous reports on conventional brachytherapy. EMBRACE is the largest prospective study on radio(chemo)therapy with MR IGABT for LACC to date and will provide a benchmark for future studies.

Proffered Papers: Proffered papers 29 : Head and neck

OC-0570 Validating gene signatures in locally advanced HNSCC patients treated by PORT-C and in xenografts S. Patil 1,2,3 , A. Linge 1,3,4,5 , B. Tawk 6,7,8 , K. Gurtner 1,3,4 , M. Großer 9 , F. Lohaus 1,3,4,5 , V. Gudziol 5,10 , A. Nowak 5,11 , I. Tinhofer 12,13 , V. Budach 12,13 , M. Stuschke 14,15 , P. Balermpas 16,17 , C. Rödel 16,17 , H. Schäfer 18,19 , A. Grosu 18,19 , A. Abdollahi 6,7,8,20,21 , J. Debus 6,8,20,21,22 , C. Belka 23,24,25 , S.E. Combs 25,26,27 , D. Mönnich 28,29 , D. Zips 28,29 , G.B. Baretton 3,5,9,30 , M. Krause 1,2,3,4,5 , M. Baumann 1,4,31 , S. Löck 1,3,4 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 Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany ; 3 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK partner site Dresden, Dresden, Germany ; 4 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 5 National Center for Tumor Diseases NCT, Partner Site Dresden, Dresden, Germany ; 6 Heidelberg Institute of Radiation Oncology HIRO, National Center for Radiation Research in Oncology NCRO- University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg, Germany ; 7 Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg, Germany ; 8 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Heidelberg, Heidelberg, Germany ; 9 Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 10 Department of Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 11 Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 12 Department of Radiooncology and Radiotherapy, Charité University Medicine, Berlin, Germany ; 13 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Berlin, Berlin, Germany ; 14 Department of Radiotherapy- Medical Faculty, University of Duisburg-Essen, Essen, Germany ; 15 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Essen, Essen, Germany ; 16 Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt, Germany ; 17 German Cancer Research Center DKFZ- Heidelberg, German Cancer Consortium DKTK- partner site Frankfurt, Frankfurt, Germany ; 18 Department of Radiation Oncology- Medical Center- Medical Faculty,