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

Clin Cancer Res. 2019 Jan 1;25(1):35-42. doi: 10.1158/1078-0432.CCR-17-3375. Epub 2018 Jun 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / veterinary
  • Cats
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Nose Neoplasms / pathology
  • Nose Neoplasms / radiotherapy*
  • Nose Neoplasms / veterinary
  • Radiotherapy / adverse effects
  • Radiotherapy / methods*
  • Radiotherapy Dosage
  • Swine
  • Swine, Miniature