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, 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

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.

Keywords: Carbon ion therapy; Photon therapy; Proton therapy; Radioresistant tumors; Radiotherapy.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Choice between photon and proton therapy in the control arm. ΔNTCP, Difference in normal tissue complication probability; LOAR, Dose limits of organs at risk; OAR, Organs at risk; RD, Recommended doses
Fig. 2
Fig. 2
Workflow diagram. ACC, Adenoid cystic carcinomas; CNAO, National Center for Oncological Hadrontherapy; MTB, Multidisciplinary tumor board

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Source: PubMed

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