ESTRO 36 Abstract Book

S533 ESTRO 36 _______________________________________________________________________________________________

Material and Methods 19 consecutive surgically resected HNSCCs were studied. WDF were collected 1 day and 3 days after surgery from the cancer operative bed. EGF, VEGF, SDF-1 and osteopontin levels were measured in WDF using enzyme- linked immunosorbent assay (ELISA) kits. Clonogenic assays were performed using Cal27 HNSCC cells irradiated with 1 to 6 Gy in presence or not of WDF and pretreated or not with cetuximab 6 hours before irradiation. Results The correlations between molecular levels and pathological cancer features showed that CXCL-12 expression was significantly increased in WDF in presence of lymph node metastasis (p<0,05), lymph node density (p<0,05) and extra capsular spread (ECS) (P<0,05). Osteopontin expression was significantly increased in presence of ECS (p<0,05). TGF-β expression was significantly reduced in presence of ECS (P<0,0000001) and for patients treated for a cancer relapse (p<0,001). Clonogenic assays evidenced that WDF reduced efficacy of irradiation on Cal27 cells with an increase of clonogenic survival compared to control (that is irradiated cells without WDF). Pretreatment of cells with cetuximab reduced surviving fraction to values comparable to control. Conclusion Preliminary data from pilot study evidenced that microenvironment in WDF favors residual tumor cell proliferation and affects response to radiation. Early treatment with biological therapies can increase radio sensitivity and improve outcome. PO-0965 Imaging of the hypoxia related marker Carbonic Anhydrase IX in human head and neck cancer xenografts F.J. Huizing 1 , B.A.W. Hoeben 1 , O.C. Boerman 2 , J. Bussink 1 1 Radboudumc, Radiation oncology, Nijmegen, The Netherlands 2 Radboudumc, Nuclear medicine, Nijmegen, The Netherlands Purpose or Objective Tumor hypoxia forms a major factor in radio- and chemoresistance in head and neck cancer and other solid tumors. Assessment of tumor hypoxia may allow patient selection for hypoxia or CAIX targeting treatment combined with radiotherapy. Recently, the radioactive tracer 111 In-girentuximab-F(ab’) 2 was designed to target the endogenous hypoxia related marker carbonic anhydrase IX (CAIX), in combination with a SPECT scan this tracer can be used for imaging. The purpose of this study was to characterize 111 In-girentuximab-F(ab’) 2 in a preclinical setting. Material and Methods First the affinity and internalization kinetics of 111 In- girentuximab-F(ab’) 2 were determined in vitro with the use of SK-RC-52 cells. The optimal timing and optimal protein dose for imaging were determined in athymic nude mice with a subcutaneous xenografted human head and neck carcinoma. Tracer uptake was measured using the U- SPECT, by analyzing ex vivo activity counting and by autoradiography of tumor sections. Immunohistochemical staining was used to validate the tracer uptake to the CAIX expression. Results In vitro 26% of the tracs internalized into the SK-RC-52 cells after 24 hours. The half maximal inhibitory concentration was 0.69 ± 0.08 nM. As optimal time between tracer injection and imaging we found 24 hours to be optimal. The protein dose of 10 microgram will result in the highest tumor to blood ratio after 24 hours. Immunohistochemical images show a distinct spatial correlation to autoradiography images (Fig. 1).

Conclusion 111 In-girentuximab-F(ab’) 2 has a high affinity to CAIX. For optimal imaging of CAIX expression in human xenografts, a tracer protein dose of 10 microgram should be administrated 24 hours before scanning. These results suggest that 111 In-girentuximab-F(ab’) 2 is a promising tracer, in ongoing studies we will assess the tracer’s applicability for treatment selection and monitoring. PO-0966 Prognostic value of tissue necrosis,CD34 MVD and CA-IX in head and neck cancer patients D. Ou 1,2 , I. Garberis 3 , J. Adam 3 , P. Blanchard 1 , F. Nguyen 1 , A. Levy 1 , O. Casiraghi 3 , P. Gorphe 4 , I. Breuskin 4 , F. Janot 4 , S. Temam 4 , J. Scoazec 3 , E. Deutsch 1 , Y. Tao 1 1 Institut Gustave Roussy, Department of Radiation Oncology, Villejuif, France 2 Fudan University Shanghai Cancer Center, Department of Radiation Oncology, Shanghai, China 3 Institut Gustave Roussy, Department of Pathology, Villejuif, France 4 Institut Gustave Roussy, Department of Head and Neck Oncology, Villejuif, France Purpose or Objective Tumor hypoxia is adversely correlated to patient prognosis. The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy or bioradiotherapy. Material and Methods In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The Kaplan–Meier method, univariate and multivariate analyses, were used to analyze the correlations between biomarker status and clinicopathological characteristics and treatment outcomes. Results We found a significant correlation between MVD and overall stage (p=0.02) and T classification (p = 0.05). CA-