Not All Tumors Are Alike: Varying Efficacy of FLASH Across Tumor Types and Oxygenation Status in Spheroid Models.
Dela R., Lemos Da Silva L., Beyer S., Sørensen BS., Poulsen P., Konradsson E., Hörberger F., Petersson K., Ceberg C., Adrian G.
OBJECTIVES: Ultra-high dose rate irradiation (UHDR) has been shown to spare normal tissue in various model systems. This study evaluates its potential to sterilize cancer cells using spheroid tumor models. METHODS: Spheroids from glioblastoma (U87), hypopharyngeal squamous cell carcinoma (two sizes, FaDusmall and FaDularge) and breast adenocarcinoma (T47D) cells were irradiated with electron beams using UHDR (>200Gy/s) or conventional dose rate (CONV,∼0.1 Gy/s) exposures under ambient or reduced oxygen (1%) conditions. U87 and FaDusmall were also irradiated with protons. Spheroids were monitored using imaging for up to 100 days to determine the dose required to cure 50% of spheroids (SCD50). These data were used to calculate dose-modifying factor estimates for UHDR at the 50% survival level (DMFSCD50). RESULTS: A total of 3,230 spheroids were analyzed. Under ambient oxygen tension, UHDR and CONV showed no significant differences in U87 (DMFSCD50=0.98, p = 0.47), FaDusmall (DMFSCD50=1.01, p = 0.75), and T47D (DMFSCD50=1.04, p = 0.25), regardless of electron or proton irradiation. Under reduced oxygen levels, significantly higher UHDR doses were required to sterilize the spheroids, with DMFSCD50 1.14 (U87, p