Determining the effects of hyperthermia on the tumor and acute normal tissue response of FLASH radiation

There is limited indication of how hyperthermia would influence the unique proposition of FLASH radiation - its ability to maintain comparable tumor response while offering protection to normal tissues. Hence, this study was designed to investigate the potential of combining FLASH radiation with hyperthermia.

Experiments were performed using female CDF1 mice, where the tumor bearing or non-tumor bearing right hind legs were irradiated with either conventional dose rate (CONV) or FLASH radiation ± hyperthermia. Hyperthermia was applied 30 minutes after radiation at 42.5°C for 60 minutes. The tumor endpoint was growth delay to three times its initial treatment volume (TGT3) and the normal tissue endpoint was an acute skin toxicity of score 2.5 and above, characterized by moderate moist desquamation and partial leg deformity.

In tumor studies, the thermal enhancement ratio (TER) was 1.68 for FLASH radiotherapy and 1.50 for conventional (CONV) radiation. In acute skin toxicity studies, the TER was slightly lower, at 1.37 for FLASH and 1.29 for CONV. The dose modifying factor (DMF) in tumor studies was 1.12 but decreased to 1.00 when hyperthermia was added. Similarly, in acute skin toxicity studies, the DMF was initially 1.53 and dropped to 1.45 with the addition of hyperthermia.

Hyperthermia significantly sensitized both the CONV and FLASH radiation, but the enhancement is comparable between the two different dose rate radiations in both tumors and normal tissues.