The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients

Purpose: Previous studies using PLASH radiotherapy (RI) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Expetirnental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called FLASH-RT and irradiation delivered at a conventional dose rate called Cony -R1',' A clinical, phase I, single -dose escalation trial (25-41 Gy) was performed in 6 cat patients with locally advanced T2/T3NOMO squarnatis cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PPS) of single-dose FLAS H-RT, Results: Using. respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (>20% dose-equivalent difference vs. Conv-RT), Three cats experienced no acute toxicity whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a inetliaii follow-up of 13.5 months, the PFS at 16 months was 84%, Conclusions: Clur results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RI in human patients. See related commentary by Harrington, p, 3