Proton therapy versus conventional radiotherapy for the treatment of cavernous sinus benign meningioma, a randomized controlled phase III study protocol (COG-PROTON-01).

Background: Proton therapy (PRT) is an innovative radiotherapeutic modality for the treatment of cancer with unique ballistic properties. The depth-dose distribution of a proton beam reduces exposure of healthy tissues to radiations, compared with photon-therapy (XRT). To date, only few indications for proton-therapy, like pediatric cancers, chordomas, or intra-ocular neoplasms, are reimbursed by Health systems. There is no published or recruiting prospective study evaluating the impact of proton-therapy or conventional irradiation on neurocognitive function for meningioma patients. Notably, long-term cognitive or ocular impact of these modern irradiation schemes remains poorly known. Yet, these patients had a long life-expectancy, and are at risk of developing long-term sequelae. Thus, according to its ballistic advantage, an improvement of patient functional outcomes and a reduction of neurocognitive long-term toxicity are expected if tissue sparing proton-therapy is used .Randomized trial seems crucial to further assess proton-therapy indication for patients with cavernous sinus meningioma.

Methods: COG-PROTON-01 is the first worldwide randomized phase III prospective study evaluating long-term toxicity of these two irradiation modalities (PRT and XRT)for the treatment of cavernous sinus meningioma. Primary objective is to compare long-term cognitive and/or functional (visual, hearing, neurological and/or endocrinological) deterioration between patients treated by fractionated proton-therapy (PRT) or photon radiotherapy (XRT), 5 years after the end of irradiation. The primary endpoint is based on the individual neurocognitive test scores (grouped into five cognitive domains: attention, executive functioning, verbal memory, working memory, information processing speed) and on visual, hearing, endocrinological and neurological evaluations, five years after radiotherapy. Eligible patients with low-grade cavernous sinus meningioma will be 1:1 randomised, with stratification on age, sex, MoCA score. Overall, the inclusion of 160 patients is planned (80 in each arm). To be considered as positive, asumming that 47% of patients will not develop long-term cognitive disabilities deficits after XRT radiotherapy,, thus at least 70% of the patients treated with PRT should not develop functional impairment. First inclusions started on September 2023 (NCT05895344 ).

Trial Registration: The study was registered on clinicaltrials.gov on June 8, 2023 with the following number: NCT05895344.