Author: Luke Connell, Nolan M. Esplen, Elise Konradsson, Albert C. Koong, Ziyi Li, Steven Hsesheng Lin, Kevin Liu, Billy W Loo, Devarati Mitra, Radhe Mohan, Emil Schueler, Takeshi Takaoka, Uwe Titt, Xiaochun Wang, Ming Yang 👨🔬
Affiliation: The University of Texas MD Anderson Cancer Center, MD Anderson, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Stanford University School of Medicine 🌍
Purpose: This study aimed to assess radiation-induced gastrointestinal (GI) toxicity in mice subjected to abdominal irradiation using protons at ultra-high-dose-rate (UHDR) and conventional dose-rates (CDR). The analysis included both shoot-through and spread-out Bragg-peak (SOBP) techniques and compared the response to mice treated with electrons under similar beam conditions.
Methods: Abdominal irradiations (12-14 Gy in a single fraction) were conducted on C57BL/6 mice using proton FLASH and proton CONV beams in both shoot-through and SOBP configurations with a synchrotron. The 87 MeV proton beam had a 2 cm diameter field size, with dose rates of 0.2 or 0.3 Gy/s and 140 or 240 Gy/s, respectively, for the shoot-through and SOBP techniques. Full abdominal irradiations with 9 MeV electrons were performed using the IntraOp Mobetron under CONV (0.2 Gy/s) and FLASH (185-225 Gy/s) conditions with a 4 × 4 cm² field size. GI toxicity was quantified using the regenerating crypt assay on samples collected 84 hours post-irradiation.
Results: Mice treated with UHDR protons experienced significantly higher toxicity than those treated with CDR protons at doses of 12-14 Gy. Under equivalent dose and dose rate conditions, there was no significant difference in GI toxicity between shoot-through and SOBP techniques, indicating that acute GI response is independent of beam delivery method. Comparing protons and electrons, normal tissue toxicity was similar under CDR conditions. However, under UHDR conditions, mice treated with electrons exhibited significantly lower toxicity than those treated with protons.
Conclusion: Under CONV conditions, protons and electrons resulted in comparable levels of GI toxicity. Electron FLASH irradiation significantly reduced toxicity compared to electron CONV irradiation, while proton FLASH irradiation led to a substantial increase in toxicity. These findings suggest that normal tissue toxicity and conditions necessary to induce the FLASH effect may depend on factors beyond mean dose-rate, including the type of radiation used.