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).
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