ESTRO 36 Abstract Book

S530 ESTRO 36 2017 _______________________________________________________________________________________________

analysis in vitro and on xenograft models and functional radiobiological analyis was applied. Results Interestingly, global gene expression analysis revealed a negative correlation of genes associated with cell motility and migration in the IR derivatives of two HNSCC cell lines, namely Cal33, FaDu. We functionally validated those findings and screened for known EMT marks from literature by functional migration assays and EMT-related protein expression in several HNSCC model cell lines and established xenografts as well as in their IR-derivatives in order to correlate the acquired findings to radiotherapy outcome. The only positive correlation was found for the initial-before therapy protein expression in vitro and in vivo for Slug, a zinc-finger protein encoded by the SNAI2 gene and c-Met, a receptor tyrosine kinase encoded by the MET gene. Functional knockdown of Slug or c-Met expression let to radiosensitization in 3-D clonogenic survival assays of several HNSCC cell lines. Conclusion Currently the expression of these molecules is scored for clinical outcome to better understand the context of EMT biomarkers for HNSCC progression and the development of a potential well-directed combinational radiochemotherapy. PO-0969 Accelerated fractionation should start early for laryngeal/ hypopharyngeal cancer. C. Terhaard 1 , N. Kasperts 1 , H. Dehnad 1 , E. Smid 1 , L. Janssen 2 , R. Wigggenraad 3 , C. Raaijmakers 1 1 UMC Utrecht, Radiation Oncology Department, Utrecht, The Netherlands 2 UMC Utrecht, Head and neck surgical oncology, Utrecht, The Netherlands 3 RCWEST- Medisch Centrum Haaglanden, radiotherapy, Den Haag, The Netherlands Purpose or Objective Accelerated repopulation during radiotherapy is a main cause of local recurrence after conventional radiotherapy for H&N cancer. Based on meta-analysis accelerated fractionation (AF) is superior to conventional fractionation. In most studies around 70 Gy is given in 6 weeks. The objective of this study is to analyze 3 AC schedules with three start points of acceleration: at week 3, 4 and 5, looking for the optimum. Material and Methods Since 1995 we treat T2-3 larynx (including bulky T2 glottic) and hypopharynx cancer with AF. Three schedules have been used. AF started in week 4 for the hyperfractionated AF (HAS, n=28), in week 3 for the ASO schedule (n=283), and in week 5 in the ARCON study (n=86). Since local control was equal 2 , results of both arms were combined. Mean follow-up was 75 months. Age ranged from 32-87 years, 25% ≥ 70 years. WHO performance was 0-1 in 95%. T2, T3,T4, was 57%, 35%, and 8%; 27% was N+. Distribution between the schedules was equal for gender, stage, WHO p. , and age. Tumor location was glottis, supraglottis and hypopharynx, in 44% 45% and 11%, respectively. Results Treatment delay was only seen in 5%, independent of the schedule. Actuarial local control rates and disease free survival rates differed significantly between the schedules (table 1). In univariate analysis actuarial local control was significantly correlated with T stage (T2,n=228, 82%, T3,n=135 79%, T4 45%),sex (female fared better), stage, and marginally significant years of treatment. Local control was equal for patients < age 70 and above (80%). In multivariate analysis the only independent prognostic factors for local control were stage, sex and treatment schedule. Independent factors for disease free survival were stage and, marginally, treatment schedule.

Fig. 1: Tumour volume, TMR max and mean ADC before and after 10 fractions of RT. Red dashed-line depicts the mean, black the median, lower and upper hinges the 25 and 75 percentile, respectively. Conclusion Intra- and intertumoural heterogeneity in hypoxia distribution and fMRI parameters were observed. FMISO uptake after irradiation decreased and ADC-value increased during radiotherapy as a surrogate for reoxygenation and lower cell density or increasing necrotic areas, respectively. Our data will be extended with various tumour models and will form the preclinical data base for the development of an integrated multiparametric prediction model for personalised RT in HNSCC. PO-0968 The Role of epithelial to mesenchymal transition (EMT) as Biomarker for Radioresistance in HNSCC I. Kurth 1,2 , D. Digomann 2 , L. Hein 2 , A. Linge 1,2,3,4 , L. Koi 5 , S. Loeck 2 , K. Maebert 2 , H. Stephan 2 , C. Peitzsch 1 , M. Krause 1,2,3,4,5 , M. Baumann 2,3,4,5,6 , A. Dubrovska 2,5 1 NCT Partnerstandort Dresden, Translationale Onkologie, Dresden, Germany 2 OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany 3 Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany 4 German Cancer Consortium DKTK Dresden, German Cancer Research Center DKFZ, Dresden, Germany 5 Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiation Oncology, Dresden, Germany 6 Deutsches Krebsforschungszentrum DKFZ, Heidelberg, Germany Purpose or Objective It is described that epithelial-to-mesenchymal transition (EMT) plays an important role in head and neck squamous carcinomas (HNSCC) progression and resistance to therapy [1] . Recent studies suggest that for instance the expression of EMT related microRNAs may cause intrinsic radioresistance in HNSCC [2] . During the process of EMT epithelial cancer cells obtain a more mesenchymal-like motile and invasive phenotype, which has been argued to sustain survival and therapy resistance of those tumor cells and facilitate cancer progression. Radiotherapy is one of the main approaches to treat HNSCC. However, tumor radioresistance often impedes the success of radiotherapy and has been found to drive tumor aggressiveness and expansion. In this study we asked the question, if radioresistant HNSCC populations display EMT features on a molecular as well as on a functional level and whether we can correlate those characteristics to

treatment outcome. Material and Methods

We used multiple irradiated HNSCC lines (IR) as an established model to investigate the traits of radioresistance [3] . Global gene expression, protein