ESTRO 37 Abstract book

S139

ESTRO 37

S. Schmidt 1,2,3,4 , A. Linge 1,2,4,5,6 , A. Zwanenburg 1,2,6,7 , S. Leger 1,2 , M. Großer 8 , F. Lohaus 1,2,5,6 , V. Gudziol 6,9 , A. Nowak 6,10 , I. Tinhofer 11,12 , V. Budach 11,12 , M. Stuschke 13,14 , P. Balermpas 15,16 , C. Rödel 15,16 , A.L. Grosu 17,18 , A. Abdollahi 19,20,21,22,23 , J. Debus 19,20,21,23,24 , C. Belka 25,26,27 , S.E. Combs 25,28,29 , D. Mönnich 30,31 , D. Zips 30,31 , G.B. Baretton 2,6,8,32 , F. Buchholz 2,33 , M. Baumann 1,2,3,5,6,7 , M. Krause 1,2,3,5,6 , S. Löck 1,2,5 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 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Dresden, Dresden, Germany 3 Institute of Radiooncology - OncoRay, Helmholtz- Zentrum Dresden – Rossendorf, Dresden, Germany 5 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany 6 National Center for Tumor Diseases NCT, partner site Dresden, Dresden, Germany 7 German Cancer Research Center, DKFZ, Heidelberg, Germany 8 Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany 9 Department of Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany 10 Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany 11 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Berlin, Berlin, Germany 12 Department of Radiooncology and Radiotherapy, Charité University Medicine, Berlin, Germany 13 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Essen, Essen, Germany 14 Department of Radiotherapy, Medical Faculty - University of Duisburg-Essen, Essen, Germany 15 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Frankfurt, Frankfurt, Germany 16 Department of Radiotherapy and Oncology, Goethe- University Frankfurt, Frankfurt, Germany 17 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Freiburg, Freiburg, Germany 18 Department of Radiation Oncology, Medical Center - Medical Faculty - University of Freiburg, Freiburg, Germany 19 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Heidelberg, Heidelberg, Germany 20 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 Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg, Germany 23 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 24 Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German

Cancer Research Center DKFZ, Heidelberg, Germany 25 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Munich, Munich, Germany 26 Department of Radiation Oncology, Ludwig- Maximilians-Universität, Munich, Germany 27 Clinical Cooperation Group - Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum Munich, Munich, Germany 28 Department of Radiation Sciences DRS - Institut für Innovative Radiotherapie iRT, Helmholtz Zentrum Munich, Neuherberg, Germany 29 Department of Radiation Oncology, Technische Universität München, Munich, Germany 30 German Cancer Research Center DKFZ - Heidelberg - and German Cancer Consortium DKTK, partner site Tübingen, Tübingen, Germany 31 Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen - Eberhard Karls Universität Tübingen, Tübingen, Germany 32 Tumour- and Normal Tissue Bank, University Cancer Centre UCC - University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany 33 Medical Systems Biology, University Cancer Centre UCC - University Hospital Carl Gustav Carus - Technische Universität Dresden, Dresden, Germany Purpose or Objective To compare and improve the performance of a hypothesis-driven 7-gene signature with a signature based on whole transcriptome analysis for the prognosis of loco- regional tumour control (LRC) in patients with HPV- negative locally advanced head and neck squamous cell carcinoma (HNSCC) after postoperative radiochemotherapy (PORT-C). Material and Methods Gene expression analyses were performed on a multicentre retrospective cohort of 125 patients with HPV16 DNA negative HNSCC using the GeneChip® Human Transcriptome Array 2.0 (Affymetrix) for whole transcriptome analysis. To identify a gene signature prognostic for LRC from the whole transcriptome data, 3085 genes were considered, which previously have been related to radioresistance or response to radiotherapy [1- 4]. Internal cross validation was used to compare different signature sizes, feature selection algorithms and prognostic models and to identify the final gene signature. The performance of the whole transcriptome- based signature was compared to a previously identified 7-gene signature based on nanoString analysis of a hypothesis-driven gene set containing 171 genes, using the concordance index (ci). The signatures were applied independently to stratify patients into groups of low (LR) and high (HR) risk of recurrence. Finally, a combined high risk group was defined, including patients who were classified as high risk patients by both gene signatures. Results The identified gene signature based on whole transcriptome data showed improved performance (ci: 0.79-0.87) compared to the signature based on the hypothesis-driven gene set (ci: 0.72-0.78) and contained genes related to tumourigenesis, invasion, cell cycle regulation and immune response. Patient stratification into low and high risk groups was performed for both signatures, see figure A and B. The difference between LR and HR regarding LRC was highly significant (p<0.001) between both groups. Compared to the 7-gene nanoString signature, the LR group showed a slightly improved LRC for the Affymetrix-based signature, similar to that of HPV positive tumours. The combined high risk group showed a poor LRC of only about 45%, see figure C.