Abstract Book

S1262

ESTRO 37

Material and Methods Pretreatment tumour biopsies from 100 OTSCC patients were immunostained for Aurora-A and Aurora-B. Log rang test and Kaplan Meier were performed for the analysis of survival. Aurora-kinases expression and additional clinicopathological variables were included in the multivariate analysis (MVA) using a backward Cox regression strategy. Results Of 89 patients initially treated with surgery, 57, 15, 4 and 13 were diagnosed with Stages I, II III and IV, respectively. Eleven patients with clinical stage IV were initially treated with chemoradiation. With a median follow-up of 75 months, the 5-year OS and DFS of all patients were 57% and 50%, respectively. Of 100 patients, 26 had Aurora-A positive tumours, whereas 47 tumours expressed Aurora-B. Median OS was significantly shorter in patients with Aurora-A positive (105 months vs 27 months, p=0.019) and Aurora-B positive (not reached vs 32 months, p=0.0037) tumours. No difference in DFS was observed. MVA identified Aurora-A expression, Aurora-B expression, age and stage as significant predictors of OS. The magnitudes of the hazards for OS associated with Aurora-A and Aurora-B were 2.7 (95%CI 1.17-6.27, p=0.02) and 2.43 (95%CI 1.13-5.26, p=0.02), respectively. Conclusion Pretreatment Aurora-A and Aurora-B expression identifies a subset of OTSCC patients with increased risk of death. These findings could help in patient selection and represent an encouraging step toward the development of personalized therapeutic approaches. EP-2286 CHK1-mediated replication fork stabilization confers radioresistance in HR deficient tumor cells I. Bold 1 , A. Specht 1 , A. Parplys 1 , W. Mansour 1 , K. Rothkamm 1 , T. Clauditz 2 , A. Münscher 3 , A. Friedl 4 , H. Pospiech 5 , C. Petersen 6 , K. Borgmann 7 1 Laboratory of Radiobiology and Experimental Radiooncology, Department of Radiotherapy and Radiooncology University Medical Center Hamburg- Eppendorf, Hamburg, Germany 2 Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 3 Department of Orothinolaryngolgoy and Head and Neck Surgery, Department of Radiotherapy and Radiooncology University Medical Center Hamburg-Eppendorf, Hamburg, Germany 4 Department of Radiation Oncology-, Ludwig Maximilians University, Munich, Germany 5 Leibniz Institute for Age Reasearch, Fritz Lipmann Institute, Jena, Germany 6 Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 7 Laboratory of Radiobiology and Experimental Radiooncology-, Department of Radiotherapy and Radiooncology- University Medical Center Hamburg- Eppendorf, Hamburg, Germany Purpose or Objective Replication-dependent radio sensitization of tumors are one of the promising tools for future improvements in the therapy of head and neck cancer cells (HNSCCs). To cope with the complex situation during replication, response pathways have been described that promote fork stabilization, inhibition of origin firing and lesion repair. However, the network of the interacting proteins that underlies the DNA repair and checkpoint systems in damaged S-phase cells after irradiation remains to be

elucidated. Therefore, the main objective of this project was to elucidate the molecular events that enable and coordinate replication and repair processes including fidelity mechanisms acting at the replication fork in irradiated S-phase cells. This is of great importance to identify new candidates for enhancing the therapeutic ratio achieved by radiotherapy. Material and Methods Experiments were carried out in ten HNSCCs. Cellular sensitivity was tested after irradiation ± CHK1/MRE11 inhibitor or siRNA against CHK1/MRE11. Replication processes were estimated by the DNA Fiber assay. Protein expression levels were performed by Western Blot analysis. Results Here we show that properly activated CHK1 protects cells from DNA damage at replication forks using DNA Fiber assay without restoring homologous recombination activity at DNA double strand breaks measured by plasmid reconstruction assay. Instead, its presence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. Treatment of cells with siRNA and inhibitors against CHK1 and MRE11 confirmed that CHK1 protects nascent DNA at stalled replication forks after irradiation. Conclusion Therefore our observations indicate that CHK1 inhibitors are eligible candidates to enhance the therapeutic ratio achieved by radiotherapy in the treatment of HR- deficient tumors. EP-2287 Prognostic value of dynamic changes of neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma D. Ou 1,2 , X. Wang 1,2 , M. Wu 1,2 , F. Xue 1,2 , X. He 1,2 , C. Hu 1,2 1 Fudan University Shanghai Cancer Center, Department of Radiation Oncology, Shanghai, China 2 Shanghai Medical College- Fudan University, Department of Oncology, Shanghai, China Purpose or Objective To investigate the prognostic value of dynamic changes between pre-treatment and post-treatment factors in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Material and Methods Between September 2005 to October 2012, 112 patients with LANPC treated with sequential chemoradiotherapy were prospectively enrolled. Clinical and pathological data, both before initiation of induction chemotherapy (pre-IC) and 1 month after completion of radiotherapy (post-RT) were fully collected in 103 patients and these patients were included in the final analysis. Cox regression analysis was used to analyze the correlations of various clinicopathological factors at different time points with treatment outcomes. The robustness of prognostic performance of the clinicopathological factors was assessed using 10-fold cross validation. Results During median follow-up of 70 months (range: 36–116 months), 29 patients developed recurrences and 19 died. Progression-free survival (PFS) and overall survival (OS) at 5 years were 75.3% and 81.4%, respectively. There were no significant differences of pre-IC peripheral leukocyte, neutrophil, lymphocyte, monocyte or platelet count, hemoglobin, lactate dehydrogenase (LDH), albumin (ALB) level, or neutrophil-lymphocyte ratio (NLR) between recurrent patients and non-recurrent patients (p>0.05).