ESTRO 2023 - Abstract Book

S1998

Digital Posters

ESTRO 2023

PO-2221 The effect of Ultra-High Dose-Rate Carbon ion irradiation to cell invasion on breast tumor cells.

K. Oniwa 1 , K. Minami 2 , M. Yagi 3 , S. Shimizu 3 , M. Koizumi 2 , K. Ogawa 2 , T. Kanai 4

1 Osaka University Graduate School of Medicine , Radiation Oncology, Suita, Osaka, Japan; 2 Osaka University Graduate School of Medicine, Radiation Oncology, Suita, Osaka, Japan; 3 Osaka University Graduate School of Medicine, Department of Carbon Ion Radiotherapy Graduate School of Medicine, Suita, Osaka, Japan; 4 Osaka Heavy Ion Therapy Center, Radiation Oncology, Osaka, Japan Purpose or Objective Currently, the normal tissue sparing and local tumor control at ultra-High Dose-Rate (uHDR) irradiation have been reported with electron, photons, and proton. Additionally, cellar responses or in vivo experiment using uHDR with heavy ions have been gradually reported. Our research group is interested in the effect of radiation to metastatic potentials on irradiated cells. In present, the effect of uHDR to tumor cell metastatic potentials is still little known. Here, we focused on the comparison of cell invasive capabilities between uHDR and conventional irradiated cells with carbon ion beam on breast cancer cell lines. Materials and Methods Triple negative human breast cancer cell line MDA-MB-231 and estrogen positive human breast tumor cell line MCF-7 were used in this study. The cells irradiated at uHDR (> 90 Gy/sec) and conventional dose rate (CDR) (1.6 Gy/min) with carbon ion beam. Matrigel invasion assays were conducted using living cells after 24 hours from carbon ion irradiation. Invaded cells were counted with microscope. Results At uHDR irradiation of 1.6 Gy compared to non-irradiation (0Gy), the invasion cells were significantly reduced both cell lines. The inhibited ratios of invasive capabilities with uHDR on MDA-MB-231 and MCF-7 were 73.3% and 77.7%, respectively. At CDR irradiation, there was no difference in invasive capability between 0 Gy and 1.6 Gy. The inhibited ratios of invasive capabilities with CDR on MDA-MB-231 and MCF-7 were 3.94% and 20.1%, respectively. Conclusion We confirmed the cellar invasive potential in human breast cancer cell lines by uHDR and CDR irradiation with carbon ion beams. Our results suggested that there was a significantly difference in the effect to cell invasive capability between uHDR and CDR. Remarkably, even if low dose can inhibit the one of the metastatic potentials on breast cancer cells with uHDR. We are currently studying the molecular mechanism in this phenomenon and would like to discuss in this presentation. 1 Centre for Energy Research, Environmental Physics Department, Budapest, Hungary; 2 Budapest University of Technology and Economics, Department of Physical Chemistry and Materials Science, Budapest, Hungary; 3 Centre for Energy Research, Environmental Physics Department , Budapest, Hungary; 4 ELTE Eötvös Loránd University, Doctoral School of Physics, Budapest, Hungary Purpose or Objective Low dose hyper-radiosensitivity (HRS) and induced radioresistance (IRR) can be observed in the dose dependence of survival of many different cell lines.. While the phenomenon may have implications on both tumour control and normal tissue complication probabilities, its fundamental causes remain unclear. Earlier, it was hypothesised that low dose HRS is derived from a protective mechanism that has evolved to prevent genomic instability by removing those cells at risk of mutation. The objectives of the present study are to set up a computational model based on this hypothesis and to test its predictions with experimental data (1,2). Materials and Methods The computational model considers mutagenic lesions occurring spontaneously during cell divisions (mean number is m in # per cell division) and mutagenic lesions induced directly by radiation (with a factor of µ in 1/Gy). Positions of cells are selected randomly on a virtual disk representing the culture dish. Cells emit signals to their environment with a strength proportional to the number of mutagenic lesions, which decreases with the distance. A cell goes into apoptosis if its mutagenic lesion number is higher than the sum of the mean number of mutations per cell division and the mean number of mutagenic lesions detected by the signal strength in the environment of the given cell. Surviving curves are determined supposing that the number of mutagenic lesions follows Poisson distribution with a mean proportional to absorbed dose. Monte-Carlo simulations were performed to fit the parameters ( m and µ ) to 101 experimental datasets. Results The computational model can reproduce the local minimum of surviving curves without introducing any arbitrary thresholds like a critical dose. The model can be fitted well to experimental datasets resulting in reasonable values for its two parameters. In general, the model fails to fit experimental data in those cases when the Induced Repair (IR) model, the most frequently used, descriptive mathematical model also fails. PO-2222 In silico model for low dose hyper-radiosensitivity linking mutation induction and cell survival B. Madas 1,2 , S. Polgár 3,4