TY - JOUR
T1 - Ultra-high dose rate effect on circulating immune cells
T2 - A potential mechanism for FLASH effect?
AU - Jin, Jian Yue
AU - Gu, Anxin
AU - Wang, Weili
AU - Oleinick, Nancy L.
AU - Machtay, Mitchell
AU - (Spring) Kong, Feng Ming
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8
Y1 - 2020/8
N2 - Purpose: “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 the ultra-high dose rate FLASH-RT significantly reduces the killing of circulating immune cells which may partially contribute to the reported FLASH effect. Methods: 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 ultra-high vs. conventional dose rates. Results: A strong sparing effect on circulating blood cells by FLASH-RT was noticed; i.e., killing of circulating immune cells reduced from 90% to 100% at conventional dose rates to 5–10% at ultra-high dose rates. The threshold FLASH dose rate was determined to be ~40 Gy/s 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 sparing effect increased with the dose/fraction, reached a plateau at 30–50 Gy/fraction, and almost completely vanished at 2 Gy/fraction. Conclusion: We have calculated a strong sparing effect on circulating immune cells by FLASH-RT, which may contribute to the reported FLASH effects in animal studies.
AB - Purpose: “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 the ultra-high dose rate FLASH-RT significantly reduces the killing of circulating immune cells which may partially contribute to the reported FLASH effect. Methods: 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 ultra-high vs. conventional dose rates. Results: A strong sparing effect on circulating blood cells by FLASH-RT was noticed; i.e., killing of circulating immune cells reduced from 90% to 100% at conventional dose rates to 5–10% at ultra-high dose rates. The threshold FLASH dose rate was determined to be ~40 Gy/s 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 sparing effect increased with the dose/fraction, reached a plateau at 30–50 Gy/fraction, and almost completely vanished at 2 Gy/fraction. Conclusion: We have calculated a strong sparing effect on circulating immune cells by FLASH-RT, which may contribute to the reported FLASH effects in animal studies.
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U2 - 10.1016/j.radonc.2020.04.054
DO - 10.1016/j.radonc.2020.04.054
M3 - Article
C2 - 32387486
AN - SCOPUS:85084752584
SN - 0167-8140
VL - 149
SP - 55
EP - 62
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -