ESTRO 36 Abstract Book

S533 ESTRO 36 2017 _______________________________________________________________________________________________

2 University of Naples Federico II, Department of Physics, Napoli, Italy 3 Azienda Ospedaliera Universitaria Federico II, Radiation Oncology Department, Napoli, Italy 4 National Council of Research CNR, Institute of Biostructures and Bioimaging, Napoli, Italy Purpose or Objective The innovative radiotherapy techniques such as Intensity- Modulated Radiation Therapy (IMRT) and Volumetric- Modulated Arc Therapy (VMAT) allow for more conformity of dose to the tumor target and sparing of healthy tissues. However, these techniques require an increase of monitor units (MUs) and therefore an increase of treatment/delivery times for each fraction. In addition, a higher dose outside the field caused by photons scattering in the flattening filter (FF) is expected. Flattening Filter- Free (FFF) photon beams can deliver higher dose rates and reduce the treatment time by about a factor 4 compared to conventional photon beams. Additional benefits also include reduced head scatter, a lower peripheral dose and neutron contamination. Purpose of the present study is to compare the radiobiological effects of FFF versus FF photon beams in mammary epithelial tumor cells (MCF7). Material and Methods MCF7 cells were irradiated with conventional and FFF 6MV photon beams using a TrueBeamSTx (Varian Medical Systems). Different dose rate values were considered (600 MU/min and 1400 MU/min). The cells were exposed to 0.25, 0.5, 1.0, 2.0 and 4.0 Gy doses. The number of monitor units required to deliver the desired doses to the cells was calculated using Pinnacle 3 (Philips) Treatment Planning System (TPS). Irradiations were performed with the flasks placed on 5 cm of equivalent water phantom (RW3) slabs and gantry angle at 180° to deliver homogeneous dose to the cell layer. A check of the actual dose delivered to cells was done exposing 9 thermo- luminescent dosimeters (LiF:Mg,Ti TLD-100) placed on the bottom of one of the irradiated flask. Clonogenic cell survival of MCF7 cells was determined. Cell survival data were fitted to linear-quadratic model. Results In the investigated dose range (0-4Gy), no statistically significant differences on breast cancer cell survival curves was observed a) with or without flattening filter (600 MU/min vs. 600 FFF MU/min) and b) at different dose rates (600 FFF MU/min vs 1400 FFF MU/min). Cell survival curves are reported in figure 1.

Conclusion Our preliminary results suggest that the use of FFF beams does not influence cancer cell survival rate when compared with standard flattened beams. The effects of higher dose per fraction have to be further investigated. PO-0973 Dimensionality reduction of clonogenic survival data to identify candidates for radiosensitization N. Brix 1 , R. Hennel 1 , C. Belka 1 , K. Lauber 1 1 LMU University Hospital Grosshadern, Department of Radiation Oncology, Munich, Germany Purpose or Objective With approximately 70,000 new cases per year in Germany, breast cancer is the most common malignancy in women. Together with surgery and chemotherapy, the majority of patients is undergoing radiotherapy. While stratification by clinicopathological parameters – such as hormone receptor and Her2 expression – is part of the clinical routine, biomarkers for tumor radioresistance and targets for radiosensitization are currently not available. The colony formation assay represents a versatile tool to analyze cellular radiosensitivity in vitro making it indispensable for the identification of factors involved in tumor cell radioresistance. As an alternative to the linear- quadratic model, we propose a novel approach of dimensionality reduction to fully exploit the information obtained from clonogenic survival assays which allows, for instance, correlation with gene expression data. Material and Methods Clonogenic survival of 13 breast cancer cell lines and normal human mammary epithelial cells upon irradiation with 0-8 Gy was analyzed in colony formation assays. The data derived thereof were subjected to linear-quadratic fitting and principal component analysis (PCA) to extract scores of radioresistance for each cell line. Next, mRNA expression levels of more than 40 DNA damage response (DDR) regulators were measured by qRT- PCR. In order to identify predictors of radioresistance and potential targets for radiosensitization, mRNA expression levels were correlated with the PCA-derived radioresistance scores.