ESTRO 35 Abstract-book

ESTRO 35 2016 S279 ______________________________________________________________________________________________________

2 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Dresden, Dresden, Germany 3 Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology, Dresden, Germany 5 Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Department of Radiation Oncology, Dresden, Germany 6 Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Department of Otorhinolaryngology, Dresden, Germany 7 Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Department of Oral and Maxillofacial Surgery, Dresden, Germany 8 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Berlin, Berlin, Germany 9 Charité University Hospital, Department of Radiooncology and Radiotherapy, Berlin, Germany 10 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Essen, Essen, Germany 11 Medical Faculty- University of Duisburg-Essen, Department of Radiotherapy, Essen, Germany 12 Goethe-University Frankfurt, Department of Radiotherapy and Oncology, Frankfurt am Main, Germany 13 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Frankfurt, Frankfurt am Main, Germany 14 Department of Radiotherapy and Oncology, Goethe- University Frankfurt, Frankfurt am Main, Germany 15 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Freiburg, Freiburg, Germany 16 University of Freiburg- Germany, Department of Radiation Oncology- Clinical Study Section, Freiburg, Germany 17 University of Freiburg, Department of Radiation Oncology, Freiburg, Germany 18 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Heidelberg, Heidelberg, Germany 19 University of Heidelberg Medical School and German Cancer Research Center DKFZ, Translational Radiation Oncology, Heidelberg, Germany 20 University of Heidelberg Medical School and German Cancer Research Center DKFZ, National Center for Tumor Diseases NCT, Heidelberg, Germany 21 University of Heidelberg Medical School- Heidelberg Ion Therapy Center HIT, Department of Radiation Oncology, Heidelberg, Germany 22 University of Heidelberg Medical School and German Cancer Research Center DKFZ, Heidelberg Institute of Radiation Oncology HIRO- National Center for Radiation Research in Oncology NCRO, Heidelberg, Germany 23 University of Heidelberg Medical School and German Cancer Research Center DKFZ, Clinical Cooperation Unit Radiation Oncology, Heidelberg, Germany 24 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Munich, München, Germany 25 Ludwig-Maximilians-Universität, Department of Radiotherapy and Radiation Oncology, München, Germany 26 Technische Universität München, Department of Radiation Oncology, München, Germany 27 Department of Radiation Oncology, Technische Universität München, München, Germany 28 German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Tübingen, Tübingen, Germany 29 Faculty of Medicine and University Hospital Tübingen- Eberhard Karls Universität Tübingen, Department of Radiation Oncology, Tübingen, Germany 30 University Hospital Carl Gustav Carus- Technische Universität Dresden, Tumour- and Normal Tissue Bank- University Cancer Centre UCC, Dresden, Germany 31 Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Institute of Pathology, Dresden, Germany

32 University Hospital Carl Gustav Carus- Technische Universität Dresden, University Cancer Centre UCC- Medical Systems Biology, Dresden, Germany Purpose or Objective: To determine gene signatures which predict loco-regional control (LRC) and the secondary endpoints overall survival (OS) and freedom of distant metastases (FDM) of locally advanced head and neck squamous cell carcinoma (HNSCC) after postoperative radiochemotherapy. Material and Methods: A gene expression panel of 216 genes was composed including genes which are involved in proliferation, invasion and metastasis as well as in radio(chemo)resistance associated with tumour hypoxia, cancer stem cell markers, cisplatin-resistance and DNA repair. Gene expression analysis was performed using NanoString technology on a multicentre retrospective patient cohort of 196 patients with HNSCC who received postoperative radiochemotherapy. Gene signatures with a minimal number of contributing genes were extracted, which optimally predict for LRC and the secondary endpoints OS and FDM. For the construction of these minimal signatures, different statistical methods were compared, including Cox regression with forward variable selection, boosting methods and random forests. To assess the performance of the different gene signatures and statistical methods the concordance index (CI) was evaluated using 3-fold internal cross validation. Results: The resulting gene signatures mostly contained genes related to cellular proliferation, migration, invasion, and tumour hypoxia. For all endpoints and statistical methods a cross-validated CI>0.7 could be obtained, indicating a good performance of the models. Using the linear predictor as a risk variable allowed for splitting the patient cohort into groups of good and bad prognosis. The figure exemplarily shows Kaplan-Meier curves of the total patient cohort split by the median risk variable of the gene signatures determined by Cox regression with forward variable selection for all endpoints. The difference between the survival curves is highly significant (p<0.001).