ESTRO 2020 Abstract book

S346 ESTRO 2020

association with TCD50 (figure B).The correlations between these three gene signatures were weak (R<0.2).

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 signature). This was confirmed in multivariable Cox regression including age and T stage. In the xenograft models, the gene signatures based on cancer stem cell markers, hypoxia and radiosensitivity showed a significant

Conclusion In our study, we successfully transferred gene signatures that were developed for patients with locally advanced HNSCC treated mainly by pRCTx to a patient cohort treated by PORT-C. Furthermore, cancer stem cell markers, hypoxia-associated genes and a radiosensitivity signature were able to stratify xenografts with respect to the TCD50. Since these signatures were weakly correlated, they may be considered as independent and robust biomarkers for future personalized radiotherapy of patients with locally advanced HNSCC. References: [1] Linge et al. Radiother Oncol 121: 364 (2016). [2] Shen et al. Oncol Rep 83: 3403 (2017). OC-0571 Clinical Impact of Adaptive Radiotherapy in Head and neck Cancer – A Randomized controlled trial D. Patel 1 , H. Vyas 2 , S. Vangipuram 2 , R. Purohit 1 , K. Chigurupalli 1 , S. Peter 1 , A. Vashistha 1 1 Geetanjali Medical college and Hospital, Radiation Oncology, Udaipur, India ; 2 HCG, Radiation Oncology, Mumbai, India Purpose or Objective Adaptive Radiotherapy (ART) takes into account the changes in target volume and organs at risk during the course of fractionated radiotherapy. This approach has a potential to provide reduced toxicities and improved the quality of life. This study aims to assess the clinical impact of ART in treatment of primary squamous cell carcinoma of head and neck region. Material and Methods [3] Toustrup et al. Cancer Res 71: 5923 (2011). [4] Kim et al. BMC Genomics; 13: 348 (2012). [5] Chung et al. Cancer Res; 66: 8210 (2006).