Glioblastoma Radiotherapy Using Intensity Modulated Radiotherapy (IMRT) or Proton Radiation - GRIPS Trial (Glioblastoma Radiotherapy via IMRT or Proton BeamS): A Study Protocol for a Multicenter, Prospective, Open-label, Randomized, Two-arm, Phase III Study.

Abstract Background:Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter. Methods/design:The GRIPS trial is a multicenter, prospective, open-label, randomized, two-arm, phase III study using either intensity modulated photon radiation techniques (standard arm) or proton beam radiotherapy (experimental arm). Additionally, patients are stratified according to "fractionation scheme" (normofractionated/hypofractionated), "subventricular zone involvement" (yes/no) and synchronous chemotherapy (yes/no) and the planned case number is 326 patients.Radiation therapy is performed with a dose of 30 x 2 Gy(RBE) or 33 x 1.8 Gy(RBE), or for patients treated according to the hypofractionation protocol with 15 x 2.67 Gy(RBE). A possible administration of additional chemotherapy (synchronous or adjuvant) or tumor treating fields is applied in dosage and frequency according to the therapy standard outside of this study. The primary endpoint is the cumulative rate of toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition. Discussion: Aim of the GRIPS study is to prospectively assess whether the theoretical physical advantage of proton beam radiotherapy will translate into a clinical reduction of toxicity during and in the first months after therapy.Trial registration:ClinicalTrials (NCT): NCT04752280