ESTRO 2022 - Abstract Book

S215

Abstract book

ESTRO 2022

Duisburg-Essen, Essen, Germany; 15 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Essen, Essen, Germany; 16 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Frankfurt, Frankfurt, Germany; 17 Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt, Germany; 18 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany; 19 Department of Radiation Oncology, Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany; 20 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany; 21 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; 22 Heidelberg Ion Therapy Center (HIT), Department of Radiation Oncology, University of Heidelberg Medical School, Heidelberg, Germany; 23 National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 24 Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 25 Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 26 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Munich, Munich, Germany; 27 Department of Radiotherapy and Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany; 28 Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 29 Department of RadioOncology, Technische Universität München, Munich, Germany; 30 Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 31 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Tübingen, Tübingen, Germany; 32 Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Germany; 33 German Cancer Research Center (DKFZ), Heidelberg, Heidelberg, Germany; 34 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Dresden, Dresden, Germany; 35 Institute of Radiooncology – OncoRay, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany Purpose or Objective The aim of the study was (i) to analyse whether previously identified prognostic gene signatures and a molecular-subtype classification 1 from patients with head and neck squamous cell carcinoma (HNSCC) can be applied to HNSCC xenograft models and (ii) to develop and validate a novel gene signature based on a combination of xenograft data and data from patients with HPV-negative locally advanced HNSCC who received postoperative radio(chemo)therapy (PORT-C). Materials and Methods Gene expression analysis was performed using GeneChip Human Transcriptome Array 2.0 on a cohort of 59 mice bearing xenografts of ten established human HNSCC cell lines and on a multicentre retrospective development cohort of 128 patients and an independent validation cohort of 114 patients of the German Cancer Consortium - Radiation Oncology Group (DKTK- ROG) treated with PORT-C. (i) Xenografts were stratified based on molecular subtypes and gene classifiers. The dose to control 50% of tumours (TCD50) was compared between the groups by Kruskal-Wallis or Mann-Whitney-U tests, respectively. (ii) A novel gene signature was developed based on xenograft and patient data using differential gene expression analysis. The Kaplan-Meier method was applied to estimate loco-regional control (LRC), overall survival (OS) and freedom from distant metastases (DM), which were compared using log-rank tests. Results (i) The tumour xenografts were classified into the four subtypes basal, mesenchymal, atypical and classical. Mesenchymal tumours showed significantly higher TCD50 compared to other subtypes (p<0.001). In addition, gene signatures related to hypoxia 2 and radiosensitivity 3 were significantly associated with TCD50. (ii) Based on the joint xenograft and patient data, we identified a 2-gene signature consisting of FN1 and SERPINE1. This signature was prognostic for the TCD50 in pre-clinical models (p<0.001) and for LRC (p=0.007), OS (p<0.001), and DM (p=0.001) in the independent PORT-C patient cohort. Conclusion The transferability of the molecular subtype classification and gene signatures related to hypoxia 2 and radiosensitivity 3 to pre-clinical HNSCC tumour models not only underlines their robustness but also the value of xenograft models. The developed 2-gene signature was prognostic for both, xenografts and patients, and may represent an additional promising biomarker for future individualized treatment approaches. References

[1] Walter, V. et al. PLOS One 8: e56823 (2013). [2] Toustrup, K. et al. Cancer Res 7: 5923 (2011). [3] Kim, H. S. et al. BMC Genomics 13: 348 (2012).

OC-0257 Impact of RT dose and fractionation on biomarkers of systemic immune responses in early stage NSCLC

E. Gkika 1 , E. Firat 2 , S. Adebahr 1 , I. Popp 1 , G. Radicioni 1 , J. Exner 1 , A. Rühle 1 , T. Sprave 1 , U. Nestle 1 , N. Nicolay 1 , G. Niedermann 3 , D. Duda 4 , A. Grosu 1 1 University Medical Center Freiburg, Radiation Oncology, Freiburg, Germany; 2 University Medical Center, Radiation Oncology, Radiation Biology, Freiburg, Germany; 3 University Medical Center Freiburg, Radiation Oncology, Radiation Biology, Freiburg, Germany; 4 Massachusetts General Hospital and Harvard Medical School, E. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Boston, USA Purpose or Objective Ionizing radiation is used to induce cytotoxicity in cancer, but it can also induce immune-modulatory effects, which may stimulate or inhibit anti-tumor immunity. In this prospective study, we aimed to further understand the immunomodulatory