Radiation oncology (London, England) · 2025
Preclinical validation of a clinical prototype of intraoperative electron FLASH radiotherapy equipment: key evidence for a new radiotherapy paradigm.
СтатьяВалидационное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Hao Xiaofei, Du Huan, Lin Binwei, Xia Yang, Tang Mingming, Wu Wei, Wang Decai, Zhu Yihan, Zhang Yu, Wang Jianxin, Yang Yiwei, Wu Dai, Du Xiaobo
Аннотация
BACKGROUND AND PURPOSE: This study aimed to evaluate whether the clinical prototype of intraoperative electron FLASH radiotherapy (CPIO-EFLASH), with a source-surface distance (SSD) of 50 cm, could achieve ultra-high dose rates, effectively control tumors, and trigger the FLASH tissue-sparing effect in preclinical models.
MATERIALS AND METHODS: Subcutaneous tumor-bearing mice (4T1 breast cancer, U87-MG glioma, PAN02 pancreatic cancer) and healthy C57BL/6 female mice (whole-brain, thorax, abdomen and single-leg irradiation) were subjected with ultra-high dose rate radiotherapy (UHDR-RT, ≥ 40 Gy/s), conventional doserate radiotherapy (CONV-RT,0.07 Gy/s), or sham radiotherapy (Control). We evaluated survival status, tumor growth suppression, apoptosis, proliferation, and DNA damage in tumor tissues, along with radiation-induced injuries to the brain, lung, intestine, and skin tissues.
RESULTS: The actual dose rates of UHDR-RT ranged from 192 to 473 Gy/s. No significant difference in tumor growth suppression was observed between the UHDR-RT and CONV-RT. Two months post whole-brain irradiation, UHDR-RT demonstrated better spatial learning and memory abilities compared to CONV-RT. At 120 days post whole-thorax irradiation and 90 days post whole-abdomen irradiation, the survival rates of UHDR-RT were also significantly higher. Histological analyses revealed more severe injury to lung and intestinal tissues in the CONV-RT group. Additionally, UHDR-RT exhibited milder radiation-induced skin injury from 2 to 8 weeks post-irradiation.
CONCLUSION: The CPIO-EFLASH can achieve ultra-high dose rates (≥ 40 Gy/s at an SSD of 50 cm) and trigger significant normal tissue-sparing effects. Integrating electronic FLASH technology into intraoperative radiotherapy may bring potential clinical benefits by effectively treating tumors, while minimizing radiation-induced injury to normal tissues. Our findings highlight the necessity for further clinical trials of CPIO-EFLASH in intraoperative radiotherapy.
MATERIALS AND METHODS: Subcutaneous tumor-bearing mice (4T1 breast cancer, U87-MG glioma, PAN02 pancreatic cancer) and healthy C57BL/6 female mice (whole-brain, thorax, abdomen and single-leg irradiation) were subjected with ultra-high dose rate radiotherapy (UHDR-RT, ≥ 40 Gy/s), conventional doserate radiotherapy (CONV-RT,0.07 Gy/s), or sham radiotherapy (Control). We evaluated survival status, tumor growth suppression, apoptosis, proliferation, and DNA damage in tumor tissues, along with radiation-induced injuries to the brain, lung, intestine, and skin tissues.
RESULTS: The actual dose rates of UHDR-RT ranged from 192 to 473 Gy/s. No significant difference in tumor growth suppression was observed between the UHDR-RT and CONV-RT. Two months post whole-brain irradiation, UHDR-RT demonstrated better spatial learning and memory abilities compared to CONV-RT. At 120 days post whole-thorax irradiation and 90 days post whole-abdomen irradiation, the survival rates of UHDR-RT were also significantly higher. Histological analyses revealed more severe injury to lung and intestinal tissues in the CONV-RT group. Additionally, UHDR-RT exhibited milder radiation-induced skin injury from 2 to 8 weeks post-irradiation.
CONCLUSION: The CPIO-EFLASH can achieve ultra-high dose rates (≥ 40 Gy/s at an SSD of 50 cm) and trigger significant normal tissue-sparing effects. Integrating electronic FLASH technology into intraoperative radiotherapy may bring potential clinical benefits by effectively treating tumors, while minimizing radiation-induced injury to normal tissues. Our findings highlight the necessity for further clinical trials of CPIO-EFLASH in intraoperative radiotherapy.