ESTRO 2020 Abstract book

S28 ESTRO 2020

PD-0066 A 24-miRNA signature predicting HPV status in head and neck cancer J. Heß 1,2,3 , K. Unger 1,2,3 , C. Maihoefer 2,3 , L. Schüttrumpf 2,3 , T. Heider 1,3 , P. Weber 1,3 , S. Marschner 2,3 , P. Baumeister 3,4 , A. Walch 5 , C. Woischke 6 , M. Werner 7,8,9 , B. Michael 10,11,12 , I. Tinhofer 13,14 , S.E. Combs 15,16,17 , J. Debus 18,19 , H. Schäfer 8,20 , M. Krause 10,11,21,22,23 , A. Linge 10,11,21,22 , C. Rödel 24,25 , M. Stuschke 26,27 , D. Zips 28,29 , U. Ganswindt 2,3,30 , M. Henke 8,20 , H. Zitzelsberger 1,2,3 , C. Belka 2,3,15 1 Research Unit Radiation Cytogenetics, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Munich, Germany ; 2 Department of Radiation Oncology, University Hospital- LMU Munich, Munich, Germany ; 3 Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Munich, Germany ; 4 Department of Otorhinolaryngology- Head and Neck Surgery, University Hospital- LMU Munich, Munich, Germany ; 5 Research Unit Analytical Pathology, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Munich, Germany ; 6 Institute of Pathology, Faculty of Medicine- Ludwig-Maximilians- University of Munich, Munich, Germany ; 7 Institute for Surgical Pathology, Medical Center-University of Freiburg, Freiburg, Germany ; 8 German Cancer Consortium DKTK- Partner Site Freiburg, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 9 Faculty of Medicine, University of Freiburg, Freiburg, Germany ; 10 German Cancer Consortium DKTK- Partner Site Dresden, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 11 OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 12 DKFZ, German Cancer Research Center, Heidelberg, Germany ; 13 Department of Radiooncology and Radiotherapy, Charié University Hospital Berlin, Berlin, Germany ; 14 German Cancer Consortium DKTK- Partner Site Berlin, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 15 German Cancer Consortium DKTK- Partner Site Munich, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 16 Institute of Radiation Medicine IRM, Helmholtz Zentrum München- German Research Center for Environmental Health GmbH, Munich, Germany ; 17 Department of Radiation Oncology- Klinikum rechts der Isar, Technische Universität München, Munich, Germany ; 18 Department of Radiation Oncology- Heidelberg Ion Therapy Center HIT, University of Heidelberg, Heidelberg, Germany ; 19 German Cancer Consortium DKTK- Partner Site Heidelberg, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 20 Department of Radiation Oncology- Medical Center- Faculty of Medicine, University of Freiburg, Freiburg, Germany ; 21 National Center for Tumor Diseases NCT, Partner Site Dresden, Dresden, Germany ; 22 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany ; 23 Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology – OncoRay Dresden, Dresden, Germany ; 24 Department of Radiotherapy and Oncology, Goethe- University Frankfurt, Frankfurt, Germany ; 25 German Cancer Consortium DKTK- Partner Site Frankfurt, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 26 Department of Radiotherapy, Medical Faculty- University of Duisburg-Essen, Essen, Germany ; 27 German Cancer Consortium DKTK- Partner Site Essen, and German Cancer Research Center DKFZ, Heidelberg, Germany ; 28 Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen- Eberhard Karls University Tübingen, Tübingen, Germany ; 29 German Cancer Consortium DKTK- Partner Site Tübingen, and German Cancer Research Center DKFZ,

Heidelberg, Germany ; 30 Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria Purpose or Objective High-risk human papillomavirus (HPV) driven head and neck squamous cell carcinoma (HNSCC), meanwhile regarded as a distinct clinical entity, are characterized by a considerably favorable prognosis after radio(chemo)therapy and a distinct molecular pathogenesis. microRNAs (miRNAs) act as important post- transcriptionalregulators and were shown to be of prognostic relevance in HNSCC. The aim of the study was to characterize the molecular phenotype of HPV-positive and -negative HNSCC at the miRNA and transcriptome levels. Material and Methods The HPV characterized multicentre DKTK-ROG cohort (n=128), the monocentric LMU-KKG cohort (n=102) and The Cancer Genome Atlas (TCGA) HNSCC cohort (n=244) were included. HPV status of LMU-KKG and DKTK-ROG specimens was determined using p16 immunohistochemistry in combination with HPV DNA analysis. For DKTK-ROG and TCGA, HPV status was provided by the DKTK-ROG consortium and by the GDC data portal, respectively. All LMU-KKG and DKTK-ROG patients had undergone surgical resection followed by adjuvant radio(chemo)therapy. The TCGA cohort was unselected regarding treatment modalities. For DKTK-ROG and LMU-KKG Agilent miRNA microarray data were generated, for TCGA the data were downloaded. Using lasso machine learning, a generalized linear model predicting HPV status was trained in the DKTK-ROG miRNA data set and its performance assessed in the LMU-KKG and TCGA HNSCC validation data. The prognostic value of the miRNA signature was compared to clinically defined HPV status. A subset of samples with highest (n=10) and lowest (n=10) HPV prediction scores from the LMU-KKG cohort was subjected to whole RNA sequencing followed by Gene Set Enrichment Analysis The optimal prediction model contained 24 miRNAs and predicted HPV status in the DKTK-ROG cohort with a sensitivity of 89.5% and a specificity of 96.7% (AUC: 0.94). In LMU-KKG the signature predicted HPV with a sensitivity of 73.9% and a specificity of 88.6% (AUC: 0.79) and in TCGA with a sensitivity of 48.3% and a specificity of 91.2% (AUC: 0.68). The prognostic value of the predicted HPV status with regard to all survival and disease control endpoints was comparable to that of p16-based HPV status. Gene set enrichment analysis showed an up-regulation of JAK STAT signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction in HPV-positive tumors and up-regulation of epithelial mesenchymal transition in HPV-negative tissues. Conclusion In our study we identified a robust miRNA signature predicting HPV status, which could be validated in two independent cohorts with a similar prognostic value compared to that of clinically established HPV typing. Specific pathways were shown to be associated with miRNA-derived HPV prediction score. The data provide insights into the specific molecular pathogenesis of HPV- driven and classical HNSCC tumors. PD-0067 An ex vivo assay to detect radiosensitization by PARP-inhibitors in soft tissue sarcomas M. Mangoni 1 , G. Salvatore 1 , D. Greto 2 , M. Sottili 1 , C. Talamonti 1 , V. Lorenzetti 1 , M. Aquilano 1 , A. Peruzzi 1 , V. Salvestrini 1 , L. Visani 1 , P. Bonomo 1 , M. Scorianz 3 , F. Muratori 3 , G. Scoccianti 3 , D.A. Campanacci 4 , L. Livi 1 1 University of Florence, Biomedical Experimental and Clinical Sciences, Firenze, Italy ; 2 Careggi Hospital, Radiotherapy, Firenze, Italy ; 3 Careggi Hospital, (GSEA). Results