Abstract Book

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ESTRO 37

SP-0264 Not every single paediatric patient needs to receive proton beam therapy! A. Mahajan 1 1 MD Anderson Cancer Center, Proton Therapy Center, Houston, USA Abstract text Radiotherapy is needed in the multidisciplinary management of cancer in children to improve local control, overall survival and symptom management; however, it is known that radiotherapy is associated with potential toxicities. For patients with a good long term prognosis, efforts to minimize late effects is critical and technological advances have provided opportunities improve our ability to deliver therapeutic radiation. Proton therapy is a powerful tool to improve radiotherapy delivery in an effort to decrease late effects while maintaining tumor control. There is a consistent reduction in overall radiation dose to the the patient in particular within the low and intermediate dose volumes. Children are most likely to benefit from an reduction in volume of irradiated tissue. Thousands of pediatric patients have now been treated with proton therapy and clinical evidence is now increasing to support the theoretical benefits that have been proposed through dosimetric studies. Proton therapy, however, it is not needed for all children requiring radiotherapy for management of their cancer. The patient's medical history, tumor radiosensitivity, tumor volume geometry, normal tissue anatomy, and treatment options should all be considered when considering radiation treatment modalities. In this session, we will review situations where proton therapy is not necessary, or maybe associated with higher uncertainties and risk. OC-0265 Effective tumor reoxygenation for combined treatment with radiotherapy I. Grgic 1 , F. Tschanz 1 , J. Ott 1 , S. Deschoemaeker 2 , M. Guckenberger 1 , A. Heyerick 2 , M. Pruschy 1 1 Universitätsspital Zürich, Radiation Oncology, Zürich, Switzerland 2 NormOxys, NormOxys Inc., Boston- MA, USA Purpose or Objective Reactive oxygen species are generated in response to ionizing radiation (IR) and produce amongst others irreversible DNA double-strand breaks. This IR-induced cytotoxic effect is less abundant under hypoxia and thus hypoxic cells are more resistant to IR. Hence, reoxygenation of the hypoxic tumor fraction by a combined treatment modality with a pharmaceutical agent is of high interest to reduce the required dose of IR and thereby to further minimize normal tissue toxicity. Here we investigated the combined treatment modality of the novel anti-hypoxia compound myo -inositol trispyrophosphate (ITPP) in combination with IR. Material and Methods ITPP was developed as an effector of hemoglobin lowering the oxygen/hemoglobin affinity thereby resulting in an enhanced release of oxygen e.g. in hypoxic tumors. ITPP’s capability for tumor reoxygenation was serially probed by a non-invasive hypoxia-directed ODD-luciferase-based bioimaging approach and by immunohistochemistry (pimonidazole, CAIX) in FaDu-HNSCC and A549-lung carcinoma-derived tumor xenografts. Tumor growth delay was determined on treatment with ITPP and either a single high dose fraction (10 Gy) or two fractions (2 x 10 Gy) of IR. Proffered Papers: RB 3: Imaging Hypoxia - Biology in Clinic

Results Using our in vivo bioimaging approach, we confirmed increased pO 2 starting 2 hours after ITPP application. Dose-titration studies indicated that administration of ITPP at a maximal tolerable dose of 3g/kg on two consecutive days followed by immediate irradiation 2 hours after the second application of ITPP was optimal for maximal tumor reoxygenation. Interestingly, ITPP alone did not affect the growth of tumor xenografts but significantly sensitized the tumor to IR. Immunohistochemical analysis of γH2AX foci demonstrated increased DNA damage within hypoxic tumor regions after combined treatment of ITPP/IR as compared to IR alone. Furthermore, IR-induced tumor hypoxia observed at 4 days after IR was associated with a decrease in tumor vascular density and pericyte coverage, which was prevented by combinatorial treatment with ITPP. This difference in tumor hypoxia 4 days after IR could be exploited by a second fraction of 10 Gy and resulted in a sustained delay of tumor growth in ITPP/IR treated mice. Moreover, ITPP prevented a decrease of vascular density even after two fractions of 10 Gy. Conclusion ITPP administration induces an immediate increase of oxygen availability that can be exploited by a combined treatment modality with IR as shown in our HNSCC and NSCLC tumor models. ITPP seems to protect the tumor vasculature upon IR, which may positively influence the hypoxia status. Overall, our results support the strong rationale to combine ITPP with hypofractionated radiotherapy for hypoxic tumors. OC-0266 Quantitative assessment of CAIX expression with SPECT imaging in head and neck cancer xenografts F. Huizing 1 , B.A.W. Hoeben 1 , G. Franssen 2 , O. Boerman 2 , S. Heskamp 2 , J. Bussink 1 1 UMC St Radboud Nijmegen, Radiation oncology, Nijmegen, The Netherlands 2 UMC St Radboud Nijmegen, Nuclear Medicine, Nijmegen, The Netherlands Purpose or Objective Tumor hypoxia forms a major cause of radio- and chemotherapy resistance in solid tumors. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker strongly associated with poor outcome, which makes it an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment combined with radiotherapy. Recently, the radioactive tracer 111 In-girentuximab- F(ab’) 2 was developed and validated to target CAIX for SPECT imaging. The aim of this study was to optimize quantitative microSPECT/CT of CAIX in an in vivo head Athymic mice with a subcutaneous SCCNij153 and SCCNij202 head and neck carcinoma xenografts were imaged using a microSPECT/CT. First the optimal timing and protein dose for imaging were determined. Subsequently, different acquisition settings during SPECT imaging were tested. Quantification of SPECT scans was performed using IRW® software. Tracer uptake was also measured by analyzing ex vivo radioactivity counting and autoradiography of the tumor sections. Immunohistochemical staining was used to determine CAIX expression. Finally, spatial correlation between tracer uptake as measured with autoradiography and CAIX expression was calculated. Results Optimal microSPECT/CT images were obtained at 24 hours after injection of the tracer. A protein dose of 10 mg resulted in the highest tumor-to-blood ratio after 24 hours p.i. Ex vivo measurements showed a tumor uptake and neck tumor models. Material and Methods