Assessment of effectiveness of the proton-neutron and neutron-proton exposure with additional neutron and proton doses splitting on tumor cells in vitro

The search for new ways to increase the effectiveness of combined radiation therapy of radioresistant tumors remains an urgent task. One of the promising areas is the use of a combination of protons and neutrons instead of photon-neutron irradiation. The purpose of this work was to study the effectiveness of combined proton-neutron exposure to Chinese hamster tumor cells (B14-150, fibrosarcoma). Proton irradiation was performed on the proton therapy complex “Prometheus”, neutron irradiation – on the portable neutron generator NG-14, located at the A. Tsyb MRRC. The combined effect was carried out in the “protons→neutrons” and “neutrons→protons” modes with the proton and neutron components splitted into 2-4 fractions with intervals of 1 h. The contribution of neutrons to the total dose was 30%. Cell survival after all studied schemes of combined irradiation manifested the synergistic effect. Doses splitting of both neutrons and protons resulted in significant decrease in the effectiveness of exposure. Only neutron dose splitting led to no statistically significant differences between the studied irradiation schemes. However, the sequence “neutrons→protons» showed a tendency of increasing cell survival with the increase in the number of neutron dose fractions. The observed patterns indicate the important role of the spatiotemporal distribution of damage induced by protons and neutrons, their number, complexity, and interaction during the repair process.