ESTRO 38 Abstract book

S594 ESTRO 38

Results Clonogenic survival of T98G cells followed a linear- quadratic response for X-irradiation and irradiation at the front of the BP. At the distal end of the BP, cell survival per dose was much lower and a log-linear response function was found to be a better fit. 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. The initial H2AX phosphorylation was found to be up to 4 times higher at the distal end of the BP compared to the front as measured 0.5 h after 5 Gy irradiation using the same dose-rate and proton fluence in both positions. When the cells were irradiated at the top of the BP with the same proton fluence, the dose was 22 Gy and induced similar amounts of H2AX-phosphorylation as in the distal end of the BP with 5 Gy (figure 1). While most damage was repaired for cells irradiated in the front of the BP, high amounts of residual damage were seen after 5 Gy in the distal end and for 22 Gy at the top of the BP.

type of adjuvant treatment, and nuclear expression of CCND2 at recurrence. (Table 1)

Conclusion Adjuvant treatments globally reduce expression of CCND2. To our knowledge, we are the first to demonstrate that high nuclear CCND2 expression at initial surgery is associated with higher risk of early mortality for GBM patients. These results confirm preclinical data observed in immunocompromised mice suggesting that targeting CCND2 could be promising for GBM therapy.

Poster: Radiobiology track: Radiobiology of particles and heavy ions

PO-1068 Very high yield of double strand breaks found at the distal end of the proton Bragg peak N.F.J. Edin 1 , A.M. Rykkelid 1 , A. Görgen 1 , A. Baker 1 , S. Siem 1 , K. Ytre-Hauge 2 , E. Malinen 1 1 University of Oslo, Physics, Oslo, Norway ; 2 University of Bergen, Department of Physics, Bergen, Norway Purpose or Objective While protons can be delivered more precisely with less radiation to the normal tissue than X-rays, emerging reports indicate that X-rays and protons affect cellular response pathways in different ways. The involved mechanisms include DNA repair, epigenetic modulation, immunogenicity, and regulation of cytokines and protein phosphorylation. It is therefore not possible to predict biological effects of proton irradiation from dose- response data from X-ray irradiation. In this study, we use low energy protons of 16 MeV with a high dose-averaged linear energy transfer (LET) to measure differential cellular responses at different positions in the proton Bragg Peak (BP) with varying LET. We compare measured clonogenic survival to H2AX-phosporylation at 3 different time points after proton irradiation using an experimental setup ensuring accurate dosimetric depth positioning of 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 plated on dishes were irradiated with protons in a cylindrical heater at different depths, corresponding to different position before and in the BP. Clonogenic survival was measured and the number of DNA double strand breaks was assessed by an H2AX-phosphorylation-antibody using flow cytometry at 3 different time points to measure initial damage as well as repair. LETs varied from 7.5 to 44 keV/um and 220 kV X-rays were used as reference radiation. T98G glioblastoma cells. Material and Methods

Conclusion A higher amount of more complex DNA double strand breaks is induced by high LET relative to low LET protons. This is consistent with a change in shape of the survival curves with the presence of a “shoulder” for the lower LET, which is strongly reduced for the higher LET. PO-1069 RBE calculation for hadrontherapy by the BIANCA biophysical model M.P. Carante 1 , F. Ballarini 2 1 Istituto Nazionale di Fisica Nucleare INFN, Physics Department, Pavia, Italy ; 2 University of Pavia, Physics Department, Pavia, Italy Purpose or Objective The main purpose of the present work consists of comparing RBE values calculated by the BIANCA model for V79 cells (often used for hadrontherapy beam characterization) and AG01522 cells (considered as representative of normal tissues) exposed to different charged particles (protons, C-ions and He-ions) with the corresponding experimental values, and showing examples of applications to hadrontherapy beams. Material and Methods BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) is a two-parameter biophysical model that calculates the probability of radiation-induced cell death as well as chromosome aberrations, which can be regarded as indicators of normal tissue damage. The model is based on the idea that some DNA damage types (“Cluster Lesions”, where by definition each CL produces two independent chromosome fragments) lead to chromosome aberrations following distance-dependent (mis-)rejoining, or un-rejoining, of chromosome fragments, and that some aberrations lead to (clonogenic) cell death. The yield of CLs, which depends on radiation