FLASH Dose Rate Effect on Circulating Immune Cells: A Potential Mechanism for FLASH-RT?

Abstract

“FLASH” radiotherapy (RT) is a potential paradigm-changing RT technology with marked tumor killing and normal tissue sparing. However, the mechanism of the FLASH effect is not well understood. We hypothesize that FLASH-RT significantly reduces the killing of circulating immune cells which subsequently contributes to the reported FLASH effect. This computation study directly models the effect of radiation dose rate on the killing of circulating immune cells. The model considers an irradiated volume that takes up A% of cardiac output and contains B% of total blood. The irradiated blood volume and dose were calculated for various A%, B%, blood circulation time, and irradiation time (which depends on the dose rate). The linear-quadratic model was used to calculate the extent of killing of circulating immune cells at FLASH vs. conventional dose rates. A strong FLASH effect was noticed, i.e., killing of circulating immune cells reduced from 90-100% at conventional dose rates to 5-10% at FLASH dose rates. The threshold FLASH dose rate was determined to be ∼40 Gy/second for mice in an average situation (A% = 50%), consistent with the reported FLASH dose rate in animal studies, and it was approximately one order of magnitude lower for humans than for mice. The magnitude of this FLASH effect increased with the dose/fraction, reached a plateau at 30-50 Gy/fraction, and almost completely vanished at 2 Gy/fraction. We have calculated a strong FLASH effect in sparing of circulating immune cells, which may contribute to the reported FLASH effects in animal studies.