X. Lu, L. Cui, J. Lian, and L. Zhou; Southern Medical University, Guangzhou, China
Purpose/Objective(s): The efficacy of ultra-high dose rate (FLASH) radiotherapy in tumor control and reducing normal tissue damage within the irradiated area has been established. However, non-target effects often lead to varying degrees of radiation reactions in normal tissues outside the target volume. This study aims to examine the impact of FLASH and conventional (CONV) radiotherapy on abscopal normal tissues outside the target volume, and elucidate the regulatory mechanisms by which FLASH radiotherapy mitigates radiation-induced-abscopal-effects and protects normal tissues. Materials/
Methods: Four-week-old female Balb/c mice were injected with 4T1 breast cancer cells and subsequently treated with either FLASH-RT or CONV-RT at a dose of 20Gy two weeks post-injection. Survival rates and tumor regression were monitored daily for a two-week period following radiotherapy, and the mice were euthanized on day 14 to collect serum and liver tissue samples. Various biochemical, pathological, and immunological analyses were then performed to evaluate the extent of radiation-induced abscopal damage in the liver. Results: The average dose rates for FLASH-RT and CONV-RT were 625Gy/s and 0.34Gy/s, respectively. Both groups showed similar survival rates and tumor control efficacy, but the FLASH-RT group exhibited faster weight regain. Histological analysis demonstrated that the FLASH-RT group exhibited lower inflammation levels and increased recruitment of immune cells in the liver, leading to enhanced immune protection in normal liver tissues compared to the CONV-RT group. Serum biochemical analysis revealed significantly elevated activities of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) in the CONV group, indicating pronounced oxidative damage. In the CONV group, lower AST/ALT levels and higher TBIL levels were observed, suggesting impaired liver function. Additionally, elevated levels of total cholesterol (CHO) and triglycerides (TG) indicate dyslipidemia in the CONV group. In contrast, no significant differences in these parameters were observed between the FLASH group and the control group. Conclusion: FLASH radiotherapy shows potential benefits in attenuating lipid oxidative damage and modulating inflammation in non-target tissues, potentially reducing abscopal effects and radiation toxicity. This research contributes to a more comprehensive understanding of the mechanisms involved in the FLASH effect.
