3119 - Evaluation of Proton FLASH Irradiation on Cell Survival under Various Oxygen Concentrations In Vitro
Presenter(s)
S. Nomura1, N. Kamiguchi1, H. Gotou1, J. Inoue1, K. Inoue2,3, H. Yoshimura2,3, F. Isohashi2, and M. Hasegawa2,4; 1Sumitomo Heavy Industries, Ltd., Tokyo, Japan, 2Department of Radiation Oncology, Nara Medical University, Kashihara, Japan, 3Kouseikai Takai Hospital, Tenri, Japan, 4Hidaka Hospital, Takasaki, Japan
Purpose/Objective(s): Preclinical studies have demonstrated that irradiation with electrons and protons at an ultra-high dose-rate (FLASH, >40 Gy/s) spares normal tissue while maintaining tumor control. The oxygen depletion theory has been proposed as a potential mechanism underlying the FLASH sparing effect. However, there is a lack of in vitro data using protons to validate this theory. This study aimed to investigate whether the sparing effect of proton FLASH irradiation occurs under varying oxygen concentrations in vitro.
Materials/Methods: All irradiations were performed using a cyclotron-based proton therapy system. The cyclotron delivered a beam energy of 230 MeV with a maximum beam current of 200 nA. FLASH irradiation was performed using a continuous line-scanning technique to create a 60 mm× 40 mm irradiation field. For conventional dose rate (CONV) irradiation, a collimated broad beam was used to form an 80 mm× 80 mm field. Non-tumor cells (V79 and CHO-K1) and tumor cells (U-251 and A549) were irradiated at dose rates of >50 Gy/s (FLASH) or 0.1 Gy/s (CONV), with doses up to 18 Gy at the center of the spread-out Bragg peak (SOBP). Irradiations were conducted under oxygen concentrations ranging from 1.3% to 21%. Cell survival was assessed using a clonogenic assay to determine the surviving fraction. Comparison between FLASH and CONV groups was performed using the Mann-Whitney U test.
Results: The surviving fractions of V79 cells irradiated with 15 and 18 Gy at FLASH or CONV dose rates under varying oxygen concentrations are shown in Table 1. There were no significant differences in cell survival between FLASH and CONV irradiations at oxygen concentrations of 1.3%, 5%, 10%, and 21%. Similarly, no significant differences in cell survival were observed under the other cell lines investigated.
Conclusion: Proton irradiation at ultra-high dose rate (>40 Gy/s) did not induce a FLASH sparing effect on either non-tumor or tumor cells across a broad range of oxygen concentrations, from hypoxic to normoxic, under the conditions investigated. Further studies are required to explore the influence of additional factors on cell survival following FLASH irradiation.
Abstract 3119 - Table 1: Surviving fractions (SF) of V79 cells following FLASH and CONV irradiation with dose of 15 and 18 Gy under different oxygen concentrations| O2 concentration [%] | Dose [Gy] | Mean SF ± SD | p | |
| FLASH | CONV | |||
| 1.3 | 15 | 1.3×10-2±3.4×10-3 | 1.0×10-2±1.8×10-3 | 0.19 |
| 18 | 1.6×10-3±6.9×10-4 | 1.3×10-3±6.3×10-4 | 0.45 | |
| 5 | 15 | 1.3×10-3±1.1×10-4 | 1.0×10-3±2.8×10-4 | 0.40 |
| 18 | 2.6×10-4±4.7×10-5 | 2.2×10-4±3.3×10-5 | 0.37 | |
| 10 | 15 | 1.4×10-3±1.0×10-4 | 1.7×10-3±3.0×10-5 | 0.10 |
| 18 | 3.9×10-4±5.7×10-5 | 3.3×10-4±7.2×10-5 | 0.40 | |
| 21 | 15 | 1.1×10-3±2.1×10-4 | 1.2×10-3±2.4×10-4 | 0.42 |
| 18 | 2.4×10-4±7.6×10-5 | 2.8×10-4±8.6×10-5 | 0.58 | |