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application of this modality to derive potential NSCLC hypoxia biomarkers. OC-0268 FAZA PET hypoxia as a marker of loco- regional recurrence in HNSCC? Results from the DAHANCA 24 trial M. Saksø 1 , L. Mortensen 2 , H. Primdahl 2 , J. Johansen 3 , J. Kallehauge 4 , C. Hansen 5 , J. Overgaard 1 1 Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus, Denmark 2 Aarhus University Hospital, Dept. of Oncology, Aarhus, Denmark 3 Odense University Hospital, Dept. of Oncology, Odense, Denmark 4 Aarhus University Hospital, Dept. of Medical Physics, Aarhus, Denmark 5 Odense University Hospital, Laboratory of Radiation Physics, Odense, Denmark Purpose or Objective Hypoxia in head and neck squamous cell carcinoma (HNSCC) is an important risk factor when assessing clinical outcome after primary chemo-radiation (RCT). We hypothesized that the hypoxic sub-volumes are areas of the tumor with special resistance to radiation. The volumes can be visualized using molecular imaging with PET/CT and 18 F-fluoroazomycin arabinoside (FAZA). If the hypothesis is true, these areas would be predominant sites of treatment failure. The purpose of this study was 1) to report on cumulative incidence of loco-regional failures within 5 years after primary RCT in a prospective cohort and 2) to characterize the site of failure in terms of presence of hypoxia visualized by pre-treatment FAZA PET/CT. Material and Methods From 2009-2011, 40 patients with squamous cell carcinoma of the larynx, pharynx and oral cavity planned for primary RCT were included in the prospective phase II trial, DAHANCA 24. All were imaged with a static 2h-post injection FAZA PET/CT prior to treatment. The DAHANCA database were used for updates on clinical outcomes. Any recurrence was documented by both histology and imaging with MRI, PET/CT or a combination. The attenuation CT of the FAZA scan was merged with recurrence imaging and the spatial information were visually compared. Results Patients were mostly in advanced clinical stages (80% in stages III-IV) and most had oropharyngeal primaries (60%). Twenty-five of 40 patients had FAZA-avid, hypoxic tumors before treatment (63%). In total, 38 patients completed treatment as prescribed. With a median follow-up of 4.9 years, 9 loco-regional recurrences were observed, and 8 of these in patients with initially hypoxic tumors (cum. incidence of 32% and 8% respectively, p=0.04). Human Papilloma Virus-driven disease (expressed as p16-positive disease) was seen for 17 patients (43%), but in patients with recurrence for only 3 tumors, who were all hypoxic. Eight patients had recurrence imaging sufficient for co- registration with the FAZA PET/CT. Seven of these had hypoxic primary tumors, but for less than half of these patients, the recurrence was in or overlapping with the hypoxic sub-volumes. One patient had a T-site failure cranially to the initially FAZA-avid, hypoxic sub-volume. For 3 patients, failure occurred in newly developed lymph nodes not initially part of primary tumor volume (two recurrences in the elective field and one out-of-field). Conclusion The risk of loco-regional treatment failure is high for patients with hypoxic tumors as assessed by FAZA PET/CT before treatment. Hypoxia imaging with FAZA has potential for selection of patients for dose escalation, but not likely for dose painting guidance, as the pattern of failure does not convincingly support the hypothesis of

the hypoxic sub-volume being the major origin of recurrent disease. OC-0269 Comparison of tumour hypoxia measured by FMISO-PET and gene signatures for patients with HNSCC S. Löck 1,2,3 , A. Linge 1,2,3,4 , A. Seidlitz 1,2,4 , A. Bandurska- Luque 1,2,4 , M. Großer 5 , G. Baretton 3,4,5 , K. Zöphel 4,6 , D. Zips 7,8 , E. Troost 1,2,3,4,9 , M. Krause 1,2,3,4,9 , M. Baumann 1,2,3,10 1 OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden- Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany 2 Department of of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany 3 German Cancer Consortium DKTK, partner site Dresden and German Cancer Research Center, Heidelberg, Germany 4 National Center for Tumor Diseases, partner site Dresden, Dresden, Germany 5 Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany 6 Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden, Dresden, Germany 7 Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Tübingen, Germany 8 German Cancer Consortium DKTK, partner site Tübingen and German Cancer Research Center, Heidelberg, Germany 9 Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany 10 German Cancer Research Center, DKFZ, Heidelberg, Germany Purpose or Objective Tumour hypoxia is well known to increase radio- resistance of tumours. In a recent prospective biomarker imaging trial, hypoxia has been measured by [ 18 F]fluoromisonidazole positron emission tomography (FMISO-PET) scans [1,2]. Here, we compared hypoxia imaging with the expression of hypoxia-associated gene signatures for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCHT). Material and Methods FMISO-PET imaging and gene expression analyses were performed on the cohort of 50 HNSCC patients [1,2]. For this study, the FMISO-PET parameters tumour-to- background ratio (TBR peak ) and hypoxic tumour volume (HV 1.6 ) analysed before RCHT were considered. Expressions of the 15-, 26- and 30-gene hypoxia- associated signatures [3-5] were analysed from formalin- fixed paraffin-embedded (FFPE) tumour biopsies obtained before RCHT using the GeneChip® Human Transcriptome Array 2.0 (Affymetrix) and nanoString analysis. Gene expressions were compared between the two methods using the Pearson correlation coefficient. Linear regression was applied to relate TBR peak and HV 1.6 to the mean expression of the gene signatures, including the interaction with tumour volume which was assessed on the planning CT by an experienced radiation oncologist. The association of FMISO-PET parameters and gene expressions to loco-regional control (LRC) and progression-free survival (PFS) was assessed by Cox regression. Results The mean expressions of all hypoxia-associated gene signatures were highly correlated between Affymetrix and nanoString analyses (R>0.5). While TBR peak and HV 1.6 were weakly correlated with the expression of hypoxia- associated genes alone, significant correlations were