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observed if the interaction term of gene expression and tumour volume was included (R>0.5). Both FMISO-PET parameters were significantly correlated with LRC and PFS ( p <0.01), while the combination of hypoxia- associated gene expressions and their interaction with tumour volume showed a significant but weaker correlation for the 30-gene signature to LRC and for the 15- and 30-gene signature to PFS (p<0.05). The figure shows patient stratifications using HV 1.6 ( p =0.02), the 30- gene signature ( p =0.07) and their combination ( p <0.01). Conclusion Hypoxia imaging correlates with the expression of hypoxia-associated genes if the interaction of gene expression and tumour volume is included. Interestingly, both methods may complement each other, which may be of advantage for identifying patients who are at high risk of treatment failure and may benefit from dose escalation. While FMISO-PET directly measures hypoxia, the gene signatures are also associated with other radiobiologic phenomena such stemness of cancer cells. [1] Zips et al. Radiother Oncol. 2012;105:21 [2] Löck et al. Radiother Oncol. 2017;124:533 [3] Toustrup et al. Cancer Res. 2011;71:5923 [4] Eustace et al. Clin Cancer Res. 2013;19:4879 [5] Lendahl et al. Nat Rev Genet. 2009;10:821 OC-0270 Imaging tumor hypoxia in prostate cancer patients by integration of multiparametric DW-MR images T. Hompland 1 , K. Hole 2 , H. Ragnum 1 , L. Vlatkovic 3 , T. Seierstad 2 , H. Lyng 1 1 Oslo University Hospital, Radiation Biology, Oslo, Norway 2 Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo, Norway 3 Oslo University Hospital, Department of Pathology, Oslo, Norway Purpose or Objective In prostate cancer, tumor hypoxia has been ass ociated with resistance to both external radiation n and brachytherapy. A strategy to overcome the adverse effect of hypoxia could be to escalate radiation dose to the radioresistant hypoxic part of the tumor, termed hypoxia dose painting. However, no imaging tool to detect and display hypoxic tumor areas within the prostate is available for clinical use. In the present work, we propose a novel method to integrate images of oxygen consum ption and supply into a single hypoxia image. The method was developed on a cohort of prostate cancer patients based on diffusion weighted (DW)-magnetic resonance (MR) images acquired with different diffusion weighting (b-values). The hypoxia images were compared with immunostaining of the hypoxia marker pimonidazole in whole-mount sections of the prostate. Material and Methods Intermediate and high risk prostate cancer patients who were given pimonidazole 24 hours prior to prostatectomy were included. The DW-MR images were acquired on a 1.5T scanner using b-values from 0 to 1000 in steps of 100 and analyzed on a pixel-by-pixel basis with a modified bi- exponential intravoxel incoherent motion (IVIM) model. Two parameters were extracted, the fractional blood
volume, fBV, and the apparent diffusion coefficient, ADC. To investigate the physiological background of the parameters, we quantified blood vessel density (BVD) and cell density (CD) by histological analysis of whole-mount sections in 43 patients. Pimonidazole staining was evaluated by an experienced pathologist who determined a hypoxia score (HS Pimo ) for each tumor. An algorithm for pixel-wise integration of fBV and ADC images was developed in a training cohort of 43 patients and validated in an independent cohort of 51 patients. Results A significant positive correlation (R 2 =0.45) was found between fBV and BVD and a negative correlation was found between ADC and CD (R 2 =0.52). The DWI parameters therefore seemed to reflect oxygen supply and consumption, respectively. In addition, negative correlations were found between fBV and HS Pimo and between ADC and HS Pimo , suggesting that both oxygen supply and consumption are determinants of hypoxia in prostate cancer. The image integration algorithm combined ADC and fBV into a hypoxia image that was in good agreement with pimonidazole staining in histological whole-mount sections. Moreover, a strong correlation between HS Pimo and the DWI based hypoxic fraction, HF DWI , was achieved (R 2 =0.70), and this result was confirmed in the validation cohort (R 2 =0.66). Conclusion In conclusion, pixel-wise integration of the DW-MRI parameters ADC and fBV provides a promising method to quantify and visualize tumor hypoxia in prostate cancer patients that may be exploited in hypoxia dose painting. OC-0271 5-Y update of the randomized phase III trial DAHANCA19: Primary (Chemo) RT +/- zalutumumab in HNSCC J.G. Eriksen 1 , C. Maare 2 , J. Johansen 3 , H. Primdahl 4 , J. Evensen 5 , C.A. Kristensen 6 , L.J. Andersen 7 , J. Overgaard 1 1 Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus, Denmark 2 Herlev Hospital, Dept. of Oncology, Herlev, Denmark 3 Odense University Hospital, Dept. of Oncology, Odense, Denmark 4 Aarhus University Hospital, Dept. of Oncology, Aarhus, Denmark 5 Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway 6 Copenhagen University Hospital, Dept. of Oncology, Copenhagen, Denmark 7 Aalborg University Hospital, Dept. of Oncology, Aalborg, Denmark Purpose or Objective Monoclonal antibodies against the Epidermal Growth Factor receptor (EGFR-I) have been reported to increase tumor control and survival of patients with Head and Neck Squamous Cell Carcinomas (HNSCC) when combined with radiotherapy (RT). This study was conducted by the Danish Head and Neck Cancer Group (DAHANCA) and aimed to evaluate if concurrent treatment with the EGFR-I zalutumumab during chemo-RT (C-RT) or RT improved outcome in patients with HNSCC. Material and Methods 619 pts with biopsy-verified HNSCC entered the study from November 2007 to June 2012. The majority of tumors were of oropharyngeal origin (69%) whereas other sites were less represented: oral cavity (4%), hypopharynx (12%) and larynx (14%). Stratification was done by tumor-site, stage (554 (89%) patients were stage III-IV), p16-status (75% of oropharyngeal carcinomas were positive) and use of concomitant cisplatin (71%). Patients Proffered Papers: CL 5: Head and neck
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