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Background and purpose <p>This study aimed to evaluate whether the clinical prototype of intraoperative electron FLASH radiotherapy (CPIO-EFLASH), with a source-surface distance (SSD) of 50&#xa0;cm, could achieve ultra-high dose rates, effectively control tumors, and trigger the FLASH tissue-sparing effect in preclinical models.</p> Materials and methods <p>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&#xa0;Gy/s), conventional doserate radiotherapy (CONV-RT,0.07&#xa0;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.</p> Results <p>The actual dose rates of UHDR-RT ranged from 192 to 473&#xa0;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.</p> Conclusion <p>The CPIO-EFLASH can achieve ultra-high dose rates (≥ 40&#xa0;Gy/s at an SSD of 50&#xa0;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.</p>

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Preclinical validation of a clinical prototype of intraoperative electron FLASH radiotherapy equipment: key evidence for a new radiotherapy paradigm

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Xiaofei Hao,
  • Huan Du,
  • Binwei Lin,
  • Yang Xia,
  • Mingming Tang,
  • Wei Wu,
  • Decai Wang,
  • Yihan Zhu,
  • Yu Zhang,
  • Jianxin Wang,
  • Yiwei Yang,
  • Dai Wu,
  • Xiaobo Du

摘要

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.