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FLASH radiotherapy using high-energy X-rays: validation of the FLASH effect triggered by a compact single high-energy X-ray source device

Lin, B.; Du, H.; Yang, Y.; Hao, X.; Gao, F.; Liang, Y.; Tang, W.; Xu, H.; Tang, M.; Liao, Y.; Wang, D.; Lin, B.; Zhu, Y.; Zhang, Y.; Li, J.; zhou, z.; Wang, J.; Wu, D.; Du, X.

2024-07-19 cancer biology
10.1101/2024.07.16.603758 bioRxiv
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PurposeThis preclinical study aimed to verify the FLASH effect of compact single high-energy X-ray source (CHEXs) and to explore whether three irradiations with single-gantry rotation two 30 s pauses can generate FLASH effect in mice. Materials and methodsThe absolute dose and pulsed beam of the CHEXs were measured using an EBTXD radiochromic film and fast current transformer. Healthy C57BL/6J female mice and a subcutaneous tumor model were irradiated under different conditions: sham (control), FLASH-RT (FLASH1: delivering the total dose in 1 fraction; FLASH3: delivering the total dose with two 30 second pauses to simulate a three-field delivery where the gantry rotation is occurring within 30 seconds), and conventional dose rate radiotherapy (CONV-RT). Various total doses were administered to the corresponding normal tissues (whole thorax, 30 Gy; whole abdomen, 12 Gy; and skin, 36 Gy) and tumors (CT26, 16.5 Gy; and LLC, 18 Gy). Survival status, normal tissue damage, and tumor growth suppression were recorded in each group. ResultsThe average dose rate of the CHEXs exceeded 40 Gy/s. For whole-thorax and skin irradiation, both FLASH1 and FLASH3 demonstrated protective effects. For whole-abdomen irradiation, FLASH1 exhibited a superior protective effect. No significant differences in tumor growth responses were observed between the FLASH1, FLASH3, and CONV-RT groups (P>0.05). ConclusionThis study confirmed that the FLASH effect could be triggered using CHEXs FLASH radiotherapy, and demonstrated that three irradiations with single gantry rotation two 30 s pauses can trigger the FLASH effect, indicating the potential benefit of CHEXs 3D conformal radiotherapy. Our findings indicate that further clinical trials on CHEXs are warranted.

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