P02.02 Modeling of response to irradiation in recurrence glioblastoma’s cells culture

Abstract

Abstract BACKGROUND Radiosensitivity of glioblastoma (GB) cells of local relapses may be markedly different from the primary tumor. Optimal doses and regimes of re-irradiation GB recurrence is not determined yet. MATERIAL AND METHODS GO1 primary GB cell culture was obtained during removal of a recurrent tumor after combined treatment, including irradiation of the surgical bed. Сell’s culture was irradiated by photon beams with energy 6 MeV and dose rate 600 MU/min. Irradiation performed in 1, 3 and 5 fractions, by 10 different doses for each regime. The dose range was determined experimentally for one fraction (5–250 Gy); for other regimes it was calculated according to the biological equivalent dose conception (3 fractions: 5–450 Gy, 5 fractions: 5–550 Gy). The proliferative activity of cells was investigate by MTT test. The results were normalized to the control. Dose-effect curves were plotted for each irradiation regime.The experimental data were approximated by calculated curves obtained by selecting the optimal parameters of the LQ-model and it’s modification. RESULTS Irradiation of GO1 by 1 fraction with the dose 5–250 Gy, causes a slow decrease in proliferative activity, which reaches a minimum value of 23% at 150 Gy and then remains constant. After irradiation by 3 fractions, proliferative activity of the GO1 gradually decrease only at a total dose over 120 Gy and reaches 37% after 450 Gy. When GO1 was irradiated in 5 fractions, a similar dose-effect curve was obtained, gradual decrease was observed to a value of 52% in the range of 250–500 Gy. Thus, the experimental dose-effect curves for irradiation of recurrence GB cells for 3 and 5 fractions have the appreciable “shoulder”, which could be explained by increased radioresistance. When approximating the experimental data by fitting the parameters of the LQ-model, the use of α/β = 8 provided the slope of the curve, close to the experimental data. For reflecting the “shoulder” an additional summand was introduced into the mathematical expression for the number of proliferating cells - a 105 Gy for 3 fractions and 255 Gy for 5 fractions. CONCLUSION Modified LQ-model could be used for an adequate mathematical description of the effectiveness of fractionated irradiation in relapsed GB culture cells in vitro. It’s necessary to introduce a summand into the formula that determines the formation of a “shoulder” on the dose-effect curve for this. The research was supported financially by RFBR (Project No. 18-29-01061).