ESTRO 36 Abstract Book

S527 ESTRO 36 2017 _______________________________________________________________________________________________

In the present study we examined the relative sensitivity of various tumor cells in vivo and in vitro to alpha radiation and the role of DNA damage control in this effect. Material and Methods Implanted murine tumors were treated with a single 224 Ra- loaded source, and tumor progression and survival were recorded. Intratumoral alpha particle distribution was measured by the spread of 212 Pb. The sensitivity of the various cancer cells was determined by their ability to form colonies after irradiation in vitro with alpha particles. The formation and disappearance of g amma- H2AX foci (DSBs indicators), and activation of non- homologous end joining following recruitment of Ku70 into the nucleus, served to evaluate DNA damage control and - DaRT caused significant damage in vivo to squamous cell tumors (SQ2) but not to pancreatic (Panc02) and breast adenocarcinoma (4T1). - Tissue necrosis and tumor growth retardation were in correlation with the intratumoral distribution of released alpha emitting isotopes. - SQ2 cells were the most radiosensitive to alpha particles (mean lethal dose required to reduce cell viability to 37%; D 0 =0.57) while the pancreatic (D 0 =1.1) and breast cancer cells (D 0 =1.05) were less radiosensitive. - The three cell lines exhibited different damage accumulation and repair kinetics. The radio-resistant cell line 4T1 had the lowest number of double strand breaks (DSBs) and a fast recruitment of nuclear Ku70, indicating a quick and efficient repair process. The relatively radio- resistant Panc02 cells, had an intermediate number of DSBs, and fast damage repair. SQ2 cells exhibited high DNA damage and a low and very slow Ku70 nuclear recruitment, indicating a slow and not efficient repair process that consequently resulted in cell death. Conclusion The radiosensitivity of tumors to alpha radiation was in correlation with their ability to avoid or repair double strand breaks. Identifying the mechanism(s) responsible for the resistance of various tumor cells to alpha radiation may open the possibility to block this mechanism(s) and render the cells more susceptible to alpha particles. This may have practical implications for the treatment of solid tumors by DaRT. PO-0962 Proton minibeam irradiation leads to reduced acute side effects in an in-vivo mouse ear model E. Zahnbrecher 1 , M. Sammer 2 , J. Reindl 2 , C. Greubel 2 , B. Schwarz 2 , C. Siebenwirth 1,2 , D.W.M. Walsh 1,2 , K. Ilicic 1 , J.J. Wilkens 1,3 , S.E. Combs 1,3 , G. Dollinger 2 , T.E. Schmid 1,3 1 Klinikum rechts der Isar, Technische Universität München, Munich, Germany 2 Institut für angewandte Physik und Messtechnik, Universität der Bundeswehr München, Neubiberg, Germany 3 Institute of Innovative Radiotherapy, Helmholtz Zentrum München, Neuherberg, Germany Purpose or Objective In Radiation Oncology, the maximum dose which can be delivered to a certain tumor is often limited by the radiation induced damage in normal tissue surrounding the actual tumor. Proton minibeam radiotherapy aims to minimize normal tissue damage, especially in the entrance channel. Due to beam widening with increasing track length, it leads to a homogeneous dose distribution in the tumor area, which permits tumor control as in conventional proton therapy. Acute side effects of proton minibeam irradiation were examined in an in-vivo mouse ear model to account for immune system, vasculature and higher complexity. In this study, the effect of partially widened proton minibeams was investigated as occurring repair. Results

at different depths on their way through the irradiated volume. Material and Methods A total of six different minibeam sizes were applied to the ear of Balb/c mice using 20 MeV protons. The average dose of 60 Gy was distributed in 4x4 minibeams with beam sizes of σ = 0.09, 0.2, 0.31, 0.45, 0.56 and 0.9 mm and a beam- to-beam distance of 1.8 mm. Inflammatory response, i.e. ear swelling and skin reactions, were observed for 90 days after irradiation. Results The results show a link between the applied beam sizes and the dimension of acute side effects after irradiation. The largest beam sizes lead to significant inflammatory reactions such as ear swelling, erythema and desquamation within 3-4 weeks after irradiation. The maximum skin reactions were reduced with decreasing beam sizes until almost no ear swelling or other visible skin reactions to the irradiation could be detected. Conclusion Our results show that the tissue sparing effect of proton minibeams is highest for the smallest beam sizes as occurring in the superficial layers of an irradiated volume. The positive effect decreases with increasing beam size and is therefore smallest for the biggest beam size which is equivalent to a homogeneous dose as desired in the target volume. However, since all minibeams have significantly reduced acute side effects compared to broad beam irradiation, proton minibeam radiotherapy may offer various possibilities for new approaches in clinical proton radiotherapy. Supported by the DFG Cluster of Excellence: Munich- Centre for Advanced Photonics. PO-0963 RBE variations along the Bragg curve of a 200 MeV proton beam C. Vandevoorde 1 , A. Baeyens 2 , A. Vral 2 , J. Slabbert 3 1 iThemba LABS, Radiation Biophysics, Cape Town, South Africa 2 Ghent University, Basic Medical Sciences, Ghent, Belgium 3 iThemba LABS, Medical Directorate, Cape Town, South Africa Purpose or Objective A lack of strong radiobiological datasets has resulted in the clinical adoption of a fixed, generic relative biological effectiveness (RBE) of 1.1 in current proton therapy (PT). However, in the distal area of the spread-out Bragg peak (SOBP), the RBE is certainly higher than 1.1 due to the rapid decrease in proton energy, resulting in an increased linear energy transfer (LET). Therefore, the RBE was quantified at different positions of the depth-dose profile for the 200 MeV clinical proton beam at iThemba LABS. Material and Methods V-79 fibroblasts were irradiated as monolayers at the plateau, proximal, middle and distal positions, as well as in the distal edge (32% of the maximum dose) of a 7 cm SOBP. At the same time, V-79 cells were also irradiated with 60 Co γ-rays as reference radiation. α and β values were determined from the cell survival curves and the 95% confidence ellipses of these covariant parameters were compared in the analysis. Mean inactivation dose (MID) values were calculated and used for the RBE calculations. Results A large overlap in the 95% confidence ellipses was observed for proton plateau and 60 Co γ-rays, so there is no statistical significant difference in radiation quality. The MID decreases with depth from 3.65 Gy at the entrance plateau, to 3.52 Gy, 3.40 Gy and 3.15 Gy for the proximal, middle and distal position along the SOBP respectively. Since the entrance plateau results were not significantly different from 60 Co γ-rays, RBE was calculated based on the plateau MID as a reference. This resulted in RBE values of 1.04, 1.07 and 1.16 for the proximal, middle and distal positions respectively. Furthermore, a clear separation