Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

Shiraishi, Yuta*; Matsuya, Yusuke  ; Kusumoto, Tamon*; Fukunaga, Hisanori*

FLASH radiotherapy (FLASH-RT) using ultra-high dose rate ( 40 Gy/sec) is known as a new treatment which is expected to enable preserving normal tissue functions, compared to the conventional radiotherapy (CONV-RT) with high dose rate ( 6 Gy/min). To date, it is believed that the modulation of chemical processes caused by interactions between radiation tracks under FLASH-RT is a key factor in the functional preservation of normal tissues; however, the relationship between changes in chemical processes and cellular responses remains uncertain. In this study, we developed a prediction model (integrated microdosimetric-kinetic (IMK) model for FLASH-RT) taking into account of the relationship between the chemical process and the DNA damage yields (which is the initial response) under ultra-high dose rate irradiation, to investigate the cellular mechanisms. As a result, the developed model considering the chemical-processes dependent change in DNA damage yields successfully reproduced the measured cell-killing effects of both CONV-RT and FLASH-RT for various cell line types. This model development would contribute on not only precisely understanding of cellular mechanisms after FLASH-RT irradiation but also enabling the prediction of therapeutic effects with high precision.