Speaker
Descrizione
Background and Aims
Melanoma is the most lethal type of skin cancer due to its aggressive nature. Surgery and immunotherapy are the mainstay of treatment, but radiotherapy (RT) can also be a useful treatment option. FLASH-RT, which reduces radiation-induced side effects while maintaining the same level of tumor control as conventional RT, could present a paradigm shift, allowing to increase the total dose and the dose per fraction. Our aim is to test an in-vitro platform of increasing complexity of melanoma and normal cells to investigate the effects of FLASH-RT.
Methods
Normal (SGBS, HaCat, NHDF) and cancer cell lines (A375) were cultured in 2D and through a two-layered-3D-bioprinted model. A dose range of 4-16 Gy was delivered in both CONV and FLASH (240 Gy/s) mode using the "Electron-Flash", a low energy electron LINAC with a triode-gun. Biological parameters were monitored (DNA damage, membrane permeability, colony growth pattern, cell death, metabolic and energetic profile) to obtain a comparative evaluation of radiobiological effects resulting from equal doses of CONV and FLASH on both normal and cancer cells.
Results
At all doses tested FLASH and CONV-RT show equal efficacy in reducing melanoma cells survival. Normal cells prove to be radioresistant with preserved/slightly reduced survival in all conditions and a moderate FLASH effect revealed by a lower mortality at the dose of 8 Gy. SGBS adipogenesis, used as a read-out of function, was reduced by both types of RT, with CONV having a more pronounced impact.
Conclusions
Our work achieves a cross fertilization effort between the experimentation of new technologies and the implementation of the state-of-the art of FLASH-RT, demonstrating a profound difference in the response of normal and cancer cells to both CONV and FLASH-RT. Our results demonstrate that the administration of FLASH-RT would lead to therapeutic effects on the tumor but limits the damage to healthy tissues.
