Speaker
Descrizione
Aim
We aimed to assess and compare the effects of FLASH-RT and CONV-RT on tumor growth in a melanoma model and on skin toxicity and systemic responses in healthy mice.
Methods
A melanoma model was established by injecting B16F10 cells intradermally into the left leg of mice. After five days, mice were irradiated with either 19 Gy or 35 Gy using FLASH (940 Gy/s) or CONV modes with an Electron-Flash LINAC. Tumor volume, vital parameters, energy balance, metabolic and inflammatory markers were monitored. In a parallel group of healthy mice, the same doses and modalities were used to irradiate the left leg. Following irradiation, animals were monitored over time (5 wks), for skin toxicity and systemic effects.
Results
Tumor Control: Both FLASH-RT and CONV-RT effectively controlled tumor growth, with higher efficacy at the higher radiation dose (35Gy). At 35 Gy, 25% of mice presented complete tumor remission regardless of the modality. Survival rates were significantly improved in irradiated mice compared to non-irradiated controls (P<0.0001), with the group of animals irradiated at 35Gy showing an higher survival rate compared to those irradiated with 19Gy. Although both modalities present similar efficacy, FLASH -RT group shows less damage to the skin surrounding tumor.
Skin Toxicity and systemic effects on healthy mice: Healthy mice irradiated with 19 Gy experienced reduced food intake compared to control mice, with a more pronounced difference in the CONV-RT group. Alopecia and fur discoloration were also observed at an earlier time point in CONV-RT compared to the FLASH-RT group.
At 35 Gy, irradiated animals showed a lower weight gain compared to control animals, but differences between FLASH-RT and CONV-RT in food intake or body weight were not significant. Skin damage was more severe in the CONV-RT group, necessitating earlier euthanasia. CONV-RT mice had elevated IL-6 and ghrelin levels and reduced leptin and insulin levels compared to controls and FLASH RT mice
Conclusion
FLASH-RT demonstrated equivalent tumor control compared to CONV-RT with a notable sparing effect on normal tissue. The systemic markers profile indicates that CONV-RT may induce a starvation state of perceived starvation, potentially compromising long-term energy homeostasis. FLASH-RT's tissue-sparing properties merit further investigation for clinical translation.
