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

backgroundProton 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.

methodsCOG-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 registrationThe study was registered on clinicaltrials.gov on June 8, 2023 with the following number: NCT05895344.