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

Area of Science:

• Oncology
• Radiation Oncology
• Biophysics

Background:

• Ultra-high dose rate (UHDR) irradiation, also known as FLASH radiotherapy, is investigated for its potential to reduce side effects.
• The FLASH effect, observed mainly with low-linear energy transfer (LET) and high-dose irradiation, suggests differential biological responses between tumor and normal tissues.
• Understanding UHDR irradiation's impact on both tumor control and normal tissue toxicity is crucial for clinical translation.

Purpose of the Study:

• To compare the efficacy of UHDR and conventional dose rate (CONV) irradiation on tumor growth delay.
• To evaluate the differential effects of UHDR and CONV irradiation on normal tissue responses, specifically senescence and apoptosis.
• To assess the potential of UHDR irradiation in modulating normal tissue responses while maintaining tumor control.

Main Methods:

• Utilized 3D tumor spheroids (HCT116, T98G) and a normal intestinal epithelial cell line (HIEC-6).
• Irradiated samples with both UHDR and CONV at clinically relevant doses.
• Assessed tumor growth delay, cellular senescence, and apoptosis induction post-irradiation.

Main Results:

• Both UHDR and CONV irradiation resulted in comparable tumor growth delays in HCT116 and T98G spheroids, indicating similar tumor control efficacy.
• UHDR and CONV irradiation induced similar levels of senescence in HIEC-6 cells.
• UHDR irradiation showed a lower induction of apoptosis in normal HIEC-6 cells compared to CONV irradiation at relevant doses and early time points.

Conclusions:

• UHDR irradiation demonstrates comparable tumor control efficacy to CONV irradiation.
• UHDR irradiation may offer a protective effect on normal tissues by reducing apoptosis induction.
• These findings support the potential of UHDR irradiation to improve therapeutic ratios in radiation oncology.