The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients

Marie-Catherine Vozenin 1 Pauline de Fornel Kristoffer Petersson 1 Vincent Favaudon 2 Maud Jaccard 1 Jean-François Germond 1 Benoit Petit 1 Marco Burki 1 Gisèle Ferrand 3 David Patin 1 Hanan Bouchaab 1 Mahmut Ozsahin 1 François Bochud 1 Claude Bailat 1 Patrick Devauchelle 4 Jean Bourhis 1
1 CHUV - Centre Hospitalier Universitaire Vaudois [Lausanne]
2 Génotoxicologie, signalisation et radiothérapie expérimentale
3 UNIL - Université de Lausanne
4 IGDR - Institut de Génétique et Développement de Rennes
Abstract : Background - 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.Methods - Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at ultra-high dose rate called FLASH-RT and irradiation delivered at conventional dose rate called Conv-RT. A clinical-phase-I single-dose escalation trial (25-41 Gy) was performed in six cat-patients with locally-advanced T2/T3N0M0 squamous-cell-carcinoma of the nasal planum, to determine the maximal tolerated dose and progression-free survival 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 three exhibited moderate/mild transient mucositis and all cats had depilation. With a median follow-up of 13.5 months, the progression free survival (PFS) at 16 months was 84%. Conclusion - Our results confirmed the potential advantage of FLASH-RT and provide a strong rational for further evaluating FLASH-RT in human patients.
Keywords : FLASH-RT normal tissue protection phase I trial cat-patients differential effect
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Marie-Catherine Vozenin, Pauline de Fornel, Kristoffer Petersson, Vincent Favaudon, Maud Jaccard, et al.. The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients. Clinical Cancer Research, American Association for Cancer Research, In press, 25 (1), pp.35-42. ⟨10.1158/1078-0432.CCR-17-3375⟩. ⟨hal-01812514v2⟩

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