Proton therapy for adult type IDH-mutated glioma: Proglio-1, a multicenter retrospective study

Gliomas with isocitrate dehydrogenase (IDH) mutation affect young adults with a long-life expectancy. While radiotherapy is effective, studies have shown its detrimental effects on cognition and quality of life. Unlike photon radiotherapy, proton therapy better spares healthy tissue. This study aimed to report mid-term survival and toxicities of proton therapy in a multicentric cohort of adults with IDH-mutant gliomas.

We retrospectively analyzed 90 patients treated with proton therapy in France since 2016, including 60 with IDH-mutated astrocytomas and 30 with oligodendrogliomas. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier and compared with the log-rank test. Prognostic factors were assessed using univariate Cox models. Toxicities, radiation-induced-contrast-enhancement (RICE) and patterns of recurrence were evaluated.

At the time of proton therapy, World Health Organization (WHO) pathology grades 2, 3, and 4 were observed in 42%, 54%, and 3% of patients, respectively. Protons were delivered as upfront therapy in 41 patients and after recurrence in 49. After a median follow-up of 27.3 months, median OS was not reached, and median PFS was 42.5 months for the whole cohort. WHO grades 3-4 had lower PFS than WHO grade 2 (p = 0.044). Patterns of recurrence were in-field (79%), out-of-field (7%), borderline (4%), and mixed (11%). Proton therapy was well tolerated, with only three grade > 2 toxicities. RICE occurred in 23 patients, but 74% of them did not require any treatment.

Proton therapy in IDH-mutated gliomas shows a favorable mid-term tolerance and efficacy profile.