Abstract Book

S1259

ESTRO 37

Results The induced DSBs are scored according to their complexity, from the simplest (two backbones) to the most complex (multiple backbones and bases). The results show an increase in complex DSBs for increasing LET. Although, the increasing complexity is minimal across the clinical LET range and cannot solely explain the observed increase in RBE. By combining the damage and repair simulations we are able to predict misrepaired and residual DSBs following 24 hours of repair. We find that the fraction of residual DSBs at 24 hours is constant at 0.073, regardless of dose, LET, or ion species. Our simulations predict that misrepaired DSBs are strongly dependent on DSB proximity. By scoring the initial damage pattern to determine the average number of DSBs within 70 nm from any given DSB, we are able to linearly predict the fraction of misrepaired DSBs. Conclusion A series of correlations are produced relating these biological outcomes to the conventional parameters of dose and LET. The correlations are applied to the clinical example of a proton spread out Bragg peak, showing increased biological effect at the distal edge. This work presents plausible mechanisms that can explain the increasing biological effect of protons with depth. Our results also lend weight to the concept of LET optimized treatment planning for proton therapy. EP-2280 Very high relative biological effectiveness found at the distal end of the proton Bragg peak A. Rykkelid 1 , S. Siem 1 , K. Ytre-Hauge 2 , E. Malinen 3 , N. Edin 1 1 University of Oslo, Department of Physics, Oslo, Norway 2 University of Bergen, Department of Physics and Technology, Bergen, Norway 3 Oslo University Hospital, Department of Medical Physics, Oslo, Norway Purpose or Objective Although proton therapy was established clinically decades ago, there is still some controversy on the relative biological effectiveness (RBE) in and around the Bragg peak (BP) of the proton dose distribution. Here, we present RBEs from irradiations at the frontal and distal part of the proton BP using an experimental setup ensuring accurate dosimetric depth positioning of glioblastoma cells. Material and Methods A horizontal 16 MeV proton beam line for in vitro cell irradiation was constructed. The beam line consisted of a single scattering foil, a monitor chamber type 7862 (PTW, Freiburg, Germany) and an Advanced Markus ionization chamber (PTW) with a 30 micron entrance window for absolute dosimetry. T98G glioblastoma cells were cultured in vitro and studied for clonogenic survival after proton irradiation. Beam profiles were measured using EBT3-gafchromic films. Cells plated on dishes were irradiated in a cylindrical heater at two different depths, corresponding to the frontal and distal part of the Bragg peak. Dose-averaged linear energy transfers (LETs) were 7.5 and 44 keV/um, respectively. 220 kV X-rays were used as reference radiation. Doses between 2 and 12 Gy, with dose rates of about 2 Gy/min, were applied. The impact of spatial dose heterogeneity on survival estimates was assessed by the EBT3 film dosimetry

linear-quadratic response for X-irradiation and irradiation at the front of the BP (see Figure 1 for fitted lines). At the distal part, cell survival per dose was much lower and a log-linear response function was found sufficient. Comparing with X-ray response at 37 % survival, RBE values at frontal and distal end of the BP were 1.7±0.1 and 4.9 ±0.4, respectively. Using EBT3 films, the dose at the site of the cell dishes varied with up to 10 % (1 SD) for irradiations in the distal part of the BG. This changed the estimated surviving fraction by only 0.01 percentage points at 2 Gy compared to estimates using mean dose to the dish. Conclusion RBEs of up to almost 5 can be obtained in the distal part of the proton BP for glioblastoma cells. Although substantial dose heterogeneity is present at this depth, this has minor impact on surviving fraction estimates. EP-2281 Role of HIF-1α in the migration/invasion processes in response to photon and C-ion irradiations A.S. Wozny 1,2 , G. Vares 3 , T. Nakajima 4 , A. Fujimori 5 , M. Beuve 6 , G. Alphonse 1 , C. Rodriguez-Lafrasse 1 1 univ Lyon- Université Lyon 1- Umr Cnrs5822 /In2p3- IPNL- PRISME- Radiobiologie Cellulaire et Moléculaire- Faculté de Médecine Lyon-Sud, Rhone-Alpes, Oullins, France 2 Hospices Civils de Lyon, Rhone-Alpes, Pierre Benite, France 3 Advanced Medical Instrumentation Unit- Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan 4 Department of Radiation Effects Research- National Institute of Radiological Sciences- National Institute for Quantum and Radiological Science and Technology, Chiba, Japan 5 Department of Basic Medical Sciences for Radiation Damages- National Institute of Radiological Sciences, Chiba, Japan 6 Univ Lyon- Université Lyon 1- UMR CNRS5822 /IN2P3- IPNL- PRISME- PHABIO, Rhône, Villeurbane, France Purpose or Objective The survival rate of patients with HNSCC remains low due to recurrences. Metastasis, but also cancer stem cells (CSC), located in hypoxic niches, play a key role in these relapses. HIF-1α protein (Hypoxia Inducible Factor 1α), stabilized by hypoxia and radical species induced by ionizing radiations, is involved in the radio-resistance to photons but also in the epithelial mesenchymal transition (EMT). The understanding of the differential molecular mechanisms HIF-1α-dependent, involved in the EMT and induced by photons and C-ion radiations must be deepened under normoxic conditions and particularly under hypoxia in CSCs, especially since hypoxia constitutes a tumor microenvironment promoting metastases and CSCs. Material and Methods Two HNSCC cells lines, SQ20B and FaDu, and their CSCs were grown in normoxic and hypoxic (1% O 2 ) conditions. CSCs were isolated by flow cytometry cell sorting. Boyden Chambers and scratch wound assay (Incucyte®) were performed in response to photon (250kV, Lyon-Sud Medical School, Lyon, France) and carbon ion (290Mev/n, SOBP, HIMAC, NIRS, Chiba, Japan) irradiations in order to study the invasion, migration and motility. The molecular mechanisms were studied with Elisa assay and Western- Blots.

system. Results

The BP covered around 200 microns longitudinally (80-80 % width). Clonogenic survival of T98G cells followed a