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.

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.

Epidemiological study of the incidence of cancers eligible for proton or carbon ions therapy: methodology and results of recruitment estimation.

Context. Hadrontherapy is an innovative form of radiotherapy using beams of protons or carbon ions able to destroy some radio-resistant tumours. Because these tumours are highly specific amongst all cancerous tumours, it is impossible to determine the incidence of these diseases from surveillance registries. Goal. To assess, within the Rhône-Alpes region, the incidence of cancers being hadrontherapy indications. Method. Prospective, multicentre continuous data collection during 1 year, by practitioners participating to multidisciplinary tumor board. Tumours are inoperable, radio resistant, at primary stage of development, or locally recurrent, with low metastatic potential. Results. Study involved 27 healthcare centres, 52 groups of specialist practitioners. The estimated incidence of cancers eligible for hadrontherapy in the Rhône-Alpes region in 2010, that is, for 34 locations in all, is of 8.5/100 000 inhabitants. Appraisal of the low potential of metastatic progression is impeded, because these are rare diseases, whose outcome is unfamiliar to investigators. Conclusion. Future epidemiological studies will need to focus on prognosis and on the metastatic progression rate of these diseases. Indeed, there are few information available on this subject in the literature that could be used to improve preventive measures, medical care, and the surveillance of these rare cancers.