A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy – including photon and proton therapy – for the treatment of radioresistant tumors: the ETOILE trial
Jacques Balosso,
Olivia Febvey-Combes,
Annie Iung,
Hélène Lozano,
Abdoulkader Soumai Alloh,
Catherine Cornu,
Magali Hervé,
Zohra Akkal,
Michel Lièvre,
Valérie Plattner,
Francesca Valvo,
Cristina Bono,
Maria Rosaria Fiore,
Viviana Vitolo,
Barbara Vischioni,
Stéphanie Patin,
Hubert Allemand,
François Gueyffier,
Jennifer Margier,
Pascale Guerre,
Sylvie Chabaud,
Roberto Orecchia,
Pascal Pommier
Affiliations
Jacques Balosso
Centre François Baclesse, Service de radiothérapie
Olivia Febvey-Combes
Hospices Civils de Lyon, Pôle de Santé Publique
Annie Iung
Hospices Civils de Lyon, Direction de la Recherche en Santé
Hélène Lozano
Hospices Civils de Lyon, Pôle de Santé Publique
Abdoulkader Soumai Alloh
Hospices Civils de Lyon, Direction de la Recherche en Santé
Catherine Cornu
UMR 5558, Université Claude Bernard Lyon 1
Magali Hervé
Hospices Civils de Lyon, Pôle de Santé Publique
Zohra Akkal
Hospices Civils de Lyon, Pôle de Santé Publique
Michel Lièvre
UMR 5558, Université Claude Bernard Lyon 1
Valérie Plattner
Hospices Civils de Lyon, Direction de la Recherche en Santé
Francesca Valvo
Centro Nazionale di Adroterapia Oncologica
Cristina Bono
Centro Nazionale di Adroterapia Oncologica
Maria Rosaria Fiore
Centro Nazionale di Adroterapia Oncologica
Viviana Vitolo
Centro Nazionale di Adroterapia Oncologica
Barbara Vischioni
Centro Nazionale di Adroterapia Oncologica
Stéphanie Patin
Groupement Coopération Sanitaire Centre Etoile
Hubert Allemand
Caisse Nationale d’Assurance Maladie des Travailleurs Salariés
François Gueyffier
Hospices Civils de Lyon, Pôle de Santé Publique
Jennifer Margier
Hospices Civils de Lyon, Pôle de Santé Publique
Pascale Guerre
Hospices Civils de Lyon, Pôle de Santé Publique
Sylvie Chabaud
Centre Léon Bérard, Direction de la Recherche Clinique et de l’Innovation
Abstract Background Some cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy. Methods The ETOILE study is a multicenter prospective randomized phase III trial comparing carbon ion therapy to either advanced photon or proton radiotherapy for inoperable or macroscopically incompletely resected (R2) radioresistant cancers including sarcomas and adenoid cystic carcinomas. In the experimental arm, carbon ion therapy will be performed at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy. In the control arm, photon or proton radiotherapy will be carried out in referent centers in France. The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival and local control, toxicity profile, and quality of life. In addition, a prospective health-economic study and a radiobiological analysis will be conducted. To demonstrate an absolute improvement in the 5-year PFS rate of 20% in favor of carbon ion therapy, 250 patients have to be included in the study. Discussion So far, no clinical study of phase III has demonstrated the superiority of carbon ion therapy compared to conventional radiotherapy, including proton therapy, for the treatment of radioresistant tumors. Trial registration ClinicalTrials.gov identifier: NCT02838602 . Date of registration: July 20, 2016. The posted information will be updated as needed to reflect protocol amendments and study progress.