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

TLDR

Previous studies using FLASH radiotherapy (RT) 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. We compared ultrahigh dose‑rate FLASH‑RT to conventional dose‑rate RT in pig skin and conducted a phase I single‑dose escalation trial (25–41 Gy) in six cats with advanced nasal squamous cell carcinoma to assess toxicity and progression‑free survival. FLASH‑RT produced a ≥20 % dose‑equivalent reduction in acute and late toxicity, with no acute toxicity in three cats, mild transient mucositis in three, all cats showing depilation, and an 84 % progression‑free survival at 16 months. See related commentary by Harrington, p.

Abstract

Abstract Purpose: Previous studies using FLASH radiotherapy (RT) 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. Experimental 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 “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-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 median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3