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

1 janv. 2019Clinical Cancer Research

DOI : 10.1158/1078-0432.ccr-17-3375

Auteurs

Marie-Catherine Vozenin, Pauline De Fornel, Kristoffer Petersson, Vincent Favaudon, Maud Jaccard, Jean-François Germond, Benoit Petit, Marco Burki, Gisèle Ferrand, David Patin, Hanan Bouchaab, Mahmut Ozsahin, François Bochud, Claude Bailat, Patrick Devauchelle, Jean Bourhis

Résumé

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