ESTRO 36 Abstract Book

S978 ESTRO 36 2017 _______________________________________________________________________________________________

generated using two, three or four non-coplanar arcs for tumors originated in the skull base and coplanar arrangements for all other locations. Daily IGRT was performed using Exactrac X-ray 6D system and ConeBeam- CT. The gross target volume (GTV) was defined in imaging studies and a GTVpet was automatically created using a gradient method (42% SUVmax) and registered in planning CT. Diffusion MRI, contrast T1 and T2 were used to create a GTVmri. The clinical target volume (CTV) included all potential areas at risk for microscopic tumor spread, local and regional. PTVs were created adding a margin around GTVs and CTVs of 3-5mm. The average prescription dose to the GTVs was 70Gy and 54-60Gy for the CTVs. All treatment plans were planned with simultaneous integrated boost. Adaptative radiotherapy was used when necessary (17 cases). Results Mean age of the population was 60 years (24-83). Median follow-up was 30 months (range 12 to 48 months). The 3- year loco-regional control (LRC rates) was 97%. 9 patients died of distant disease progression. The dose delivered was 70Gy, 66Gy, 60Gy and 54Gy to the GTVprimary and positive nodes, GTVsuspicious nodes, CTVhigh risk, and CTVlow risk, respectively. Only 2% of the GTVs and 5% of CTVs received less than 95% of the prescribed dose. Only one patient with a larynx carcinoma (T3N2b) failed in a grossly positive node after definitive chemoradiotherapy. The remaining 37 patients experienced a complete response. No marginal failures have been observed to date. GTV targets delineated in the PET and MRI are different and complementary to each other and relative to the CT contrast, providing safer treatments while preserving the critical organs. Conclusion Accurate dose delivery is imperative in the setting of intensity modulated radiation therapy because of the sharp dose gradients generated. The proximity of tumors to critical organs requires advanced immobilization devices and the reduction of positional uncertainties. Our multidisciplinary approach in target volume definition and imaged guided radiotherapy resulted in excellent LRC and no marginal failures. The use of PETscan and MRI also demonstrated an improvement in target delineation. Electronic Poster: Radiobiology track: Normal tissue biology of the heart EP-1807 Reducing Heart Toxicity In Medulloblastoma Using Proton Therapy A. Madkhali 1,2 , M. Partridge 1 1 University of Oxford, Oncology, OXFORD, United Kingdom 2 King Saud University, Medicine, Riyadh, Saudi Arabia Purpose or Objective Radiation therapy is known to cause acute and long term side effects. Some of those side effects are a major reason of mortality in cancer survivors. Heart disease after radiotherapy for Hodgkin and breast cancer patients is a major cause for mortality that it is offsetting the benefits of treatment (EBCTCG, 2016). In this work, potential benefits of using proton therapy in treatment of medulloblastoma to reduce heart toxicity is discussed and compared with benefit gained in reduction of secondary cancer. Material and Methods Increase in risk for rate of major coronary events for 3DCRT and proton plans for a patient with medulloblastoma (MB) was calculated using published model (Darby et al,2014), the NTCP for cardiac perfusion deficits was modelled using LKB model and relevant parameters (Das et al, 2005), and finally, the mortality risk from ischemic heart disease (IHD) was modelled using relative seriality model and relevant parameters (Kallman

et al,1992, Eriksson et al,2000). Risk of mortality from radiotherapy-induced secondary cancer (SC) was modelled as well using voxel-by-voxel dose maps and models that includes cell-kill components, linear quadratic (LQ) and linear model (LIN) (Timlin et al,2015). Results The heart mean dose in 3DCRT was 16.1 Gy, and 0.1 Gy in the proton plan. Risk of major coronary events were 119% (3DCRT ), 0.7% (proton). NTCP was 34.5%(3DCRT), 0.8%(proton). Risk of mortality from IHD was 1.61%(3DCRT) and 0.01%(proton), while mortality from SC was for 3DCRT: 1.08%(LQ), 0.10%(LIN) and for proton: 0.32%(LQ) and 0.03%(LIN) Conclusion Proton therapy for MB is expected to decreases risk of major cardiac events, mortality due to IHD and mortality from RT-induced secondary cancer significantly, when compared to 3DCRT. With cardiac late side effects being a major and important clinical burden post-RT, and some would say more than secondary cancer risk, these results strengthen the argument to use proton therapy. EP-1808 The response of human induced pluripotent stem cell- derived chondrocytes to ionizing radiation E. Augustyniak 1,2 , W.M. Suchorska 1,3 1 Greater Poland Cancer Centre, Radiobiology Lab, Poznan, Poland 2 Medical University of Warsaw, The Postgraduate School of Molecular Medicine, Warsaw, Poland 3 Poznan University of Medical Sciences, Department of Electroradiology, Poznan, Poland Purpose or Objective The response of stem-derived cells to treatment with ionizing radiation (IR) is a questionable issue. It is worth mentioning that un- and differentiated cells possess different radiosensitivity. It is also unknown, whether the DDR mechanisms of stem-derived cells are more similar to those from 'parental” stem cells (SCs) or perhaps those from completely differentiated cells. Herein, we assume that differentiation process leading to obtaining of specialized cells have a significant effect on mechanisms activated in cells exposed to anticancer agents. We believe that it has a great impact on genetic stability of cells derived from SCs, what has a direct reflection in safety of application of these cells in clinical practice. The main goal of this study was to investigate the DDR of human induced pluripotent (hiPSC)-derived chondrocytes treated with IR. Material and Methods In the experiment three types of cell lines were used: hiPSCs, human articular chondrocytes and chondrocyte- like cells differentiated from hiPSCs. The investigated cells were treated with IR (0; 1; 2; 5 Gy) and collected 1, 5, 9 and 24 h after IR. Finally, the analyses of γH2AX, and PARP by flow cytometry were performed. Moreover, we investigated the level of senescence in cells treated with IR. Results These findings show that kinetics of DSBs significantly differ in hiPSCs, chondrocytes, and chondrocyte-like cells differentiated from hiPSCs. Nevertheless, the formation of DSBs in hiPSC-derived chondrocytes is similar to processes occurring in hiPSCs rather than in human articular chondrocytes. The hiPSCs and hiPSC-derived chondrocytes are very prone to DNA damage in comparison with fully mature chondrocytes. However, it is important to point out that hiPSC-derived chondrocytes possess more efficient DNA repair mechanisms resulting in the lower level of DSBs after 24h, in contrast to hiPSCs. Electronic Poster: Radiobiology track: Normal tissue radiobiology (others)