ESTRO 2020 Abstract Book

S27 ESTRO 2020

effective agents against aggressive thyroid carcinoma (TC). Material and Methods Twelve short tandem repeat (STR)-validated human TC- derived cell lines were used (ATC n=7, poorly differentiated (PDTC) n=1, papillary (PTC) n=4). All cell lines underwent comprehensive genomic characterization prior to drug testing. High-throughput drug screens were performed using the NCI’s Approved Oncology Set V (n=112) and a custom collection of agents (n=145). The effect of drugs on cell growth and survival was measured after 72 hours of drug exposure. To identify the most effective drugs, we selected individual agents with maximal growth inhibition at each dose level relative to wells examined on the day of treatment (top 25th percentile) and subsequently used non-parametric statistics to compare effect size with other drugs and controls. The concentration-response curves from biological replicates of different passage number were fitted using non-linear regression and the AUC was calculated and used for the development of pharmacologic trees. Confirmatory testing was completed for the most effective drug classes. Results The most effective classes of agents against ATC cell lines were: antimetabolites, inducers of reactive of oxygen species (ROS), proteasome and microtubule inhibitors. These agent classes in addition to HDAC inhibitors achieved the highest effectiveness for PTC cell lines at 0.1µM dose level but only proteasome and microtubule inhibitors remained effective at 0.01µM dose level. TP53 mutational status affected drug sensitivity; mutant TP53 cell lines demonstrated enhanced sensitivity to antimetabolites and Vinca alkaloids, while wild-type TP53 cell lines demonstrated preferential sensitivity to HDAC inhibitors. Likewise, BRAF mutational status affected drug sensitivity with higher sensitivity to taxanes and protein kinase inhibitors in V600E mutation compared with preferential sensitivity to proteasome and HDAC inhibitors in wild-type. Confirmatory testing validated initial screening results. Figure 1. Example of ATC cell line (MDA-T178) used in the high-throughput screen. A) Boxplots of effective drugs in the initial screen at 0.1µM concentration compared with DMSO and other ineffective drugs; B) Drug tree analysis where the size of the colored dots represents relative effectiveness of each individual agent. * indicates statistical significance P<0.0001 for both. Conclusion High-throughput screening identified classes of systemic agents, which demonstrate preferential effectiveness against aggressive TC variants, particularly those with mutant BRAF and TP53. These agents provide a basis for in vivo preclinical validation prior to clinical trial development. 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