This study investigated the hypothesis that the dose rates of radiation can affects the tumor outcome of radiotherapy (RT) to synergize with anti-PD-1 antibody.
Lewis lung carcinoma cells were injected subcutaneously into syngeneic mice at two separate sites, defined as “primary” site that was irradiated and a “secondary” site outside the radiation field. When both tumors were in a range of 50 to 100mm3, C57BL/6 male mice were randomly assigned to 3 groups receiving sham-RT (0 Gy), conventional dose-rate RT (CONV-RT), or ultra-high dose-rate RT (FLASH-RT). The dose rates of CONV-RT and FLASH-RT groups were 0.067 and 118 Gy/sec, respectively. FLASH-RT was performed using the DIRAMS LINAC, producing 6-MeV electron beams. All of the groups were treated with anti-PD1 antibodies starting at the day of irradiation and the two irradiated groups were treated with 24Gy in 1 fraction.
During the 4-week observation period, the size of tumors at the secondary site did not differ among the three groups. The size of tumors at the primary site was significantly different between the RT and sham-RT groups, but not between the two RT groups.
In this experiment, we could not confirm the abscopal effect of RT in the LL2 tumor model, and there was no difference in irradiated tumor response between FLASH-RT and CONV-RT.