1. The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients
- Author
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Maud Jaccard, Marie-Catherine Vozenin, Jean Bourhis, Marco Burki, Patrick Devauchelle, Claude Bailat, Kristoffer Petersson, François Bochud, Jean François Germond, Gisele Ferrand, David Patin, Pauline de Fornel, Benoit Petit, Vincent Favaudon, Hanan Bouchaab, Mahmut Ozsahin, Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Université de Lausanne ( UNIL ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), nd, ISREC fundation/Biletema, CR32I3L_156924, Lead Agency FNS/ANR, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Université de Lausanne (UNIL), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,Locally advanced ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,cat-patients ,030218 nuclear medicine & medical imaging ,phase I trial ,03 medical and health sciences ,0302 clinical medicine ,FLASH-RT ,medicine ,Mucositis ,Carcinoma ,CATS ,business.industry ,Cancer ,differential effect ,normal tissue protection ,medicine.disease ,Acute toxicity ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,business ,[ SDV.GEN ] Life Sciences [q-bio]/Genetics - 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
- Published
- 2018
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