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

Area of Science:

• Oncology
• Radiation Oncology
• Cell Biology

Background:

• Ultra-high dose rate (UHDR) irradiation, also known as the FLASH effect, is investigated for its potential to reduce radiation-induced side effects in healthy tissues.
• Previous studies demonstrated this protective effect primarily with low-linear energy transfer (LET) and high-dose irradiation.

Purpose of the Study:

• To compare the efficacy of UHDR and conventional dose rate (CONV) irradiation on tumor control and normal tissue responses.
• To evaluate the impact of UHDR irradiation on senescence and apoptosis in normal cells.

Main Methods:

• Utilized 3D tumor spheroids (HCT116, T98G) and a normal intestinal epithelial cell line (HIEC-6).
• Compared tumor growth delay, senescence induction, and apoptosis following UHDR and CONV irradiation at clinically relevant doses.

Main Results:

• Both UHDR and CONV irradiation resulted in comparable tumor growth delays, indicating similar tumor control efficacy.
• UHDR and CONV irradiation induced similar levels of senescence in normal cells.
• UHDR irradiation showed a lower induction of apoptosis in normal cells compared to CONV irradiation at early time points.

Conclusions:

• UHDR irradiation demonstrates potential for modulating normal tissue responses while maintaining comparable tumor control to conventional dose rates.
• Findings suggest UHDR irradiation could offer a therapeutic advantage by reducing radiation-induced side effects in healthy tissues.