ESTRO 36 Abstract Book

S544 ESTRO 36 2017 _______________________________________________________________________________________________

surface molecules CD14, CD83, CD80, CD86 and HLA-DR via flow cytometry. Functional analysis of irradiated DCs was performed through FITC-labelled phagocytosis assay. Results No major significant changes in the immune profile during differentiation of monocytes (CD14 high , CD83 low , CD86 low , CD80l ow , HLA-DR high ) into iDCs (CD83 low , CD86 low , CD80 medium , HLA-DR medium ) and mDCs (CD83 high , CD86 high , CD80 high , HLA-DR high ) were seen after treatment with different radiation doses (1x15 Gy, 5x2 Gy, 1x0.5 Gy) compared to the untreated control group. Functional analysis showed no difference in the phagocytotic capacity of irradiated iDCs and macs compared to the control group. Conclusion Our experiments reveal that after irradiation with different fractionations and doses maturation of DCs was unchanged compared to the control group. The capability for phagocytosis was unaffected after irradiation of DCs, indicating persistent functionality of the immune system. Additional RT-induced effects on the immunogenic potential of DCs will be investigated by using further functional assays (migration assay, mixed lymphocyte reaction assay). To investigate the effect of particle therapy, DCs will be irradiated with protons and carbon ions (C12) in future experiments. PO-0994 Integrin antagonistic drugs reveal different effectiveness in 2D monolayer vs. 3D spheroid culture V. Kopatz 1,2 , E. Selzer 1 , W. Dörr 1,2 1 Medical University of Vienna, Department for Radiation Oncology, Vienna, Austria 2 Medical University of Vienna, Christian Doppler Lab for Medical Radiation Research for Radiooncology, Vienna, Austria Purpose or Objective Preclinical evaluation of novel therapeutic substances, as well as the assessment of radiation effects, is frequently performed under standard 2D cell culture conditions. However, such monolayer cultures may fail with regard to representation of morphological in vivo conditions and their (radio)biological consequences. An alternative, in the latter aspect is the use of 3D in vitro models - like tumor spheroid culture - which are of intermediate complexity between standard in vitro monolayer cultures and in vivo tumor models. In spheroid culture, tumor cells grow in 3D aggregates that display greater similarity to in vivo tumor architecture and growth conditions, such as the presence of oxygen and nutrient gradients as well as more complex cellular interactions or 'in vivo-like” gene expression profiles. Depending on their size, multicellular spheroids may also display central hypoxic and/or necrotic areas and show quiescent and proliferating compartments. Thus spheroids often depict different behavior and sensitivity towards certain drugs or radiotherapeutic treatment as cells cultured as 2D monolayers. Especially for the study of surface receptors like integrins the 3D structure and environment is a critical aspect as these receptors transduce signals from the extracellular space to the inside, thus influencing different cell signaling pathways like cell survival, proliferation and invasion. Material and Methods Therefore in addition two standard 2D cell culture, 3D spheroid models were established with 518A2 and other melanoma cell lines for evaluation of their response to two different integrin antagonists, cilengitide and a novel integrin antagonist (NIA), as well as for the characterization of the effects of radiation treatment alone or in combination with the drugs. Results While in 2D cultures of 518A2 melanoma cells, the comparator substance cilengitide showed to be more

efficient than our novel compound NIA (IC50 value of 0,65µM), it had no inhibitory effect in 3D spheroid culture up to 50µM. Comparatively NIA revealed to have similar effectiveness in 2D as well as 3D cultures, both in the low micromolar range. During monitoring of spheroid growth, NIA treated spheroids initially depicted a growth retardation, before cells started to disintegrate and die. The radiosensitivity of 518A2 melanoma cells was found to be similar in both culture conditions. Conclusion Similar differences in drug response and efficacy between 2D and 3D cell culture environments have been reported for various anti-cancer substances as well as for some radiation exposure endpoints. However, other endpoints may - in a treatment-related manner - be depending on the culture system used. We thus plan to perform further comparative studies on survival-dependent aspects (apoptosis, intracellular signaling, and others) with integrin antagonists alone as well as in combination with irradiation in 2D cell culture versus 3D spheroids. PO-0995 Estimation of radiobiology parameters of infiltrative low-grade gliomas WHO Grade II. S. Milyukov 1 , Y. Lysak 2 , G. Panshin 2 , N. Kharchenko 1 , Z. Tsallagova 2 , T. Izmailov 2 1 Peoples’ Friendship University of Russia, Department of oncology and roentgenoradiology, Moscow, Russian Federation 2 Russian Scientific Center of Roentgenoradiology of Russia, Research department of innovative technologies of radiotherapy and chemoradiation treatment of malignant tumors, Moscow, Russian Federation Purpose or Objective Determine the value of radiobiological parameters of infiltrative low-grade gliomas WHO Grade II Material and Methods In total (the data from) 5 clinical studies: EORTC 22844 (Karim AB et al., 1996.), EORTC 22845 (van den Bent MJ et al., 2005), NCCTG 86-72-51 (Shaw E et al., 2002), the RTOG 9802 (Shaw EG et. al., 2012), the study on the hyperfractionated radiotherapy (Jeremic B et. al., 1998), and selected data from our database were used for the calculation radiobiological parameters of LGG. In total, our study included 870 patients. All patients received surgery (1-phase treatment) and radiotherapy (2-phase treatment). Following radiobiological parameters of radiotherapy were used for the calculation: dose per fraction, total dose of radiotherapy, total number of treatment days, 5-year progression-free survival. Results Following radiobiological parameters of infiltrative low- grade gliomas WHO Grade II were calculated: α, β, α/β, Td, D prolif, Tk, N clonogens. Following values were calculated (95% Cl): α (Gr – 1 ) = 0,096 (0,08–0,11), β (Gr –2 ) = 0,014 (0,012-0,018), α/β (Gr) = 6,8 (4,3-9,2), T d (days) = 21,3 (18,3-26,4), D prolif (Gr) = 0,27 (0,21-0,35), T k (days) = 44 (34-55), N clonogens = 2,18·10 3 (1,2-5,3) ·10 3 . Conclusion The calculated values of radiobiological parameters give a better idea of the biological properties of the low-grade gliomas and estimate as accurately as possible of the total dose of radiotherapy using a linear-quadratic model. Poster: RTT track: Patient preparation, positioning and immobilisation PO-0996 Accuracy of an optical surface monitoring device to reduce daily imaging of breast cancer patients J. Sharpe 1 , A. Tini 1 , A. Moreira 1 , I. Pytko 1 , C. Winter 1 , M. Guckenberger 1 , C. Linsenmeier 1 1 University Hospital of Zurich, Radiation Oncology Clinic, Zurich, Switzerland