The FLASH Effect in 3D and 2D Models: Preserving Tumor Control while Reducing Apoptosis in Normal Cells

Irradiation at ultra-high dose rates is gaining increased attention due to its ability to limit damage to surrounding healthy tissues, thereby preventing radiation-induced side effects. Although there are some exceptions, this protective effect (the FLASH effect) has been demonstrated in many preclinical models, primarily after low-LET irradiation and high-dose irradiation. Here, we report that both ultra-high dose rate (UHDR) and conventional dose rate (CONV) irradiations produce similar growth delays in 3D tumor spheroids (composed of HCT116 and T98G, colorectal carcinoma or glioblastoma cell lines), indicating comparable efficacy in tumor control. In normal cells (HIEC-6, a non-malignant epithelial cell line from the small intestine), UHDR and CONV irradiation induced comparable senescence, while a lower induction of apoptosis was observed after UHDR irradiation at clinically relevant doses and early time points postirradiation. Collectively, these findings highlight the potential of UHDR irradiation to modulate normal tissue responses while achieving comparable tumor control.