FLASH Bragg-peak irradiation with a therapeutic carbon ion beam: first in vivo results

Abstract

Background and purposeIn recent years, ultra-high dose rate (UHDR) irradiation has emerged as a promising innovative approach to cancer treatment. Characteristic feature of this regimen, commonly referred to as FLASH effect, demonstrated primarily for electrons, photons or protons, is the improved normal tissue sparing, while the tumor control is similar to the one of the conventional dose-rate (CDR) treatments. The FLASH mechanism is, however, unknown. One major question is whether this effect is maintained when using densely ionizing (high-LET) heavy nuclei. Materials and MethodsHere we report the effects of 20 Gy UHDR heavy ion irradiation in clinically relevant conditions, i.e., at high-LET in the spread-out Bragg peak (SOBP) of a 12C beam using an osteosarcoma mouse model. ResultsWe show that UHDR irradiation was less toxic in the normal tissue compared to CDR while maintaining tumor control. The immune activation was also comparable in UHDR and CDR groups. We observed that the gut microbiome was altered in mice injected with the tumor compared to healthy animals, but both UHDR and CDR exposures steered the metagenome toward a balanced state. ConclusionsThe results show that the FLASH effect is safe and effective in heavy ion therapy and provide an important benchmark for the current mechanistic FLASH models. Highlights- FLASH irradiation with SOBP carbon ions spares normal tissue in mouse - Tumor control, immune response, and gut microbioma changes are induced at the same extent both at conventional and ultra-high dose rate - FLASH carbon ion irradiation is a safe and effective alternative to conventional radiotherapy.