Electron ultra‐high dose rate FLASH irradiation study using a clinical linac: Linac modification, dosimetry, and radiobiological outcome
Dehuan Xie, Yi‐Chuan Li, Sai Ma, Xin Yang, Ruo‐Ming Lan, Ao‐Qiang Chen, Hongyu Zhu, Mei Yan, Li‐Xia Peng, Zuo‐Feng Li, Bi‐Jun Huang, Yan Chen, Xiaoyan Huang, Chao‐Nan Qian
Abstract
PURPOSE: Ultra-high dose rate FLASH irradiation (FLASH-IR) has been shown to cause less normal tissue damage compared with conventional irradiation (CONV-IR), this is known as the "FLASH effect." It has attracted immense research interest because its underlying mechanism is scarcely known. The purpose of this study was to determine whether FLASH-IR and CONV-IR induce differential inflammatory cytokine expression using a modified clinical linac. MATERIALS AND METHODS: An Elekta Synergy linac was used to deliver 6 MeV CONV-IR and modified to deliver FLASH-IR. Female FvB mice were randomly assigned to three different groups: a non-irradiated control, CONV-IR, or FLASH-IR. The FLASH-IR beam was produced by single pulses repeated manually with a 20-s interval (Strategy 1), or single-trigger multiple pulses with a 10 ms interval (Strategy 2). Mice were immobilized in the prone position in a custom-designed applicator with Gafchromic films positioned under the body. The prescribed doses for the mice were 6 to 18 Gy and verified using Gafchromic films. Cytokine expression of three pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukin-6 [IL-6]) and one anti-inflammatory cytokine (IL-10) in serum samples and skin tissue were examined within 1 month post-IR. RESULTS: Gy/s and a dose per pulse over 2 Gy at a source-to-surface distance (SSD) of 13 to 15 cm. The achieved dose coverage was 90%-105% of the maximum dose within -20 to 20 mm in the X direction and 95% within -30 to 30 mm in the Y direction. The absolute deviations between the prescribed dose and the actual dose were 2.21%, 6.04%, 2.09%, and 2.73% for 6, 9, 12, and 15 Gy as measured by EBT3 films, respectively; and 4.00%, 4.49%, and 2.30% for 10, 14, and 18 Gy as measured by the EBT XD films, respectively. The reductions in the CONV-IR versus the FLASH-IR group were 4.89%, 10.28%, -7.8%, and -22.17% for TNF-α, IFN-γ, IL-6, and IL-10 in the serum on D6, respectively; 37.26%, 67.16%, 56.68%, and -18.95% in the serum on D31, respectively; and 62.67%, 35.65%, 37.75%, and -12.20% for TNF-α, IFN-γ, IL-6, and IL-10 in the skin tissue, respectively. CONCLUSIONS: Ultra-high dose rate electron FLASH caused lower pro-inflammatory cytokine levels in serum and skin tissue which might mediate differential tissue damage between FLASH-IR and CONV-IR.