Redefining FLASH RT: the impact of mean dose rate and dose per pulse in the gastrointestinal tract

Kevin Liu; Trey Waldrop; Edgardo Aguilar; Nefetiti Mims; Denae Neill; Abagail Delahoussaye; Ziyi Li; David Swanson; Steven H Lin; Albert C Koong; Cullen M Taniguchi; Billy W Loo Jr; Devarati Mitra; Emil Schüler

doi:10.1016/j.ijrobp.2024.10.009

Redefining FLASH RT: the impact of mean dose rate and dose per pulse in the gastrointestinal tract

Int J Radiat Oncol Biol Phys. 2024 Oct 16:S0360-3016(24)03466-7. doi: 10.1016/j.ijrobp.2024.10.009. Online ahead of print.

Authors

Affiliations

¹ Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
² Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁴ Division of Basic Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: [email protected].
⁵ Division of Basic Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁶ Department of Radiation Oncology & Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA USA.
⁷ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: [email protected].
⁸ Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA. Electronic address: [email protected].

PMID: 39424078
DOI: 10.1016/j.ijrobp.2024.10.009

Abstract

Background: The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited.

Purpose: We sought to systematically evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).

Methods: C57BL/6J mice received total abdominal irradiation (11-14 Gy, single fraction) through either conventional irradiation (low DPP and low MDR, CONV) or through various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. DPPs ranging from 1 Gy to 6 Gy were evaluated while the total dose and MDR (>100 Gy/s) were kept constant; the effects of MDR were evaluated for the range 0.3-1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay.

Results: Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to an increase in sparing (an increase in number of regenerating crypts), with a more prominent effect seen at 12 and 14 Gy TAI. Interestingly, at DPPs of >4 Gy, similar level of crypt sparing was demonstrated irrespective of the MDR used (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV irrespective of MDR. However, at a lower DPP of 0.93 Gy, a MDR of 104 Gy/s produced a greater survival effect compared to 0.3 Gy/s. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model.

Conclusions: This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.