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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.

http://clincancerres.aacrjournals.org/content/25/1/3?iss=1

Author information

Vozenin MC#1, De Fornel P#2, Petersson K#3,4, Favaudon V5, Jaccard M3,4, Germond JF4, Petit B3, Burki M6, Ferrand G7, Patin D4, Bouchaab H3, Ozsahin M3,7, Bochud F4, Bailat C4, Devauchelle P#2, Bourhis J#3,7.
1
Radio-Oncology Laboratory, Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland. marie-catherine.vozenin@chuv.ch.
2
Micen-vet, Créteil, France.
3
Radio-Oncology Laboratory, Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland.
4
Institute of Radiation Physics (IRA), Lausanne University Hospital, Lausanne, Switzerland.
5
Institut Curie, INSERM U1021/CNRS UMR3347, Université Paris-Sud, Orsay, France.
6
Service de Chirurgie Expérimentale, Département de chirurgie et anesthésie, Lausanne University Hospital, Lausanne, Switzerland.
7
UNIL, Lausanne, Switzerland.
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Contributed equally