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    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.