FLASH Bragg-Peak Irradiation With a Therapeutic Carbon Ion Beam: First In Vivo Results
Walter Tinganelli, Anggraeini Puspitasari-Kokko, Olga Sokol, Alexander Helm, Palma Simoniello, Christoph Schuy, Sylvie Lerchl, Denise Eckert, Julius Oppermann, Anna Rehm, Stefan Janssen, Denise Engel, Ralf Moeller, Rossana Romano, Felix Horst, Daria Boscolo, Claudia Fournier, Marco Durante, Uli Weber
Abstract
PURPOSE: In 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, whereas 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. METHODS MATERIALS: C beam using an osteosarcoma mouse model. RESULTS: We show that UHDR irradiation was less toxic in the normal tissue compared with CDR while maintaining tumor control. The immune activation was also comparable in UHDR and CDR groups. Both UHDR and CDR exposures steered the metagenome toward a balanced state. CONCLUSIONS: These results suggest that the UHDR irradiations can improve the safety and effectiveness of heavy ion therapy, and provide a crucial benchmark for current mechanistic FLASH models. However, additional experiments are needed to validate these findings across other animal and tumor models.