Glioblastoma radiotherapy using Intensity modulated Radiotherapy (IMRT) or proton Radiotherapy—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 concurrent chemotherapy (yes/no) and the planned case number is 326 patients. Radiation therapy is performed with a dose of 30 × 2 Gy(RBE) or 33 × 1.8 Gy(RBE), or for patients treated according to the hypofractionation protocol with 15 × 2.67 Gy(RBE). A possible administration of additional chemotherapy (concurrent 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.

Systematic Review of WHO Grade 4 Astrocytoma in the Cerebellopontine Angle: The Impact of Anatomic Corridor on Treatment Options and Outcomes

“…Moreover, when treating benign tumors in the CPA, improved rates of hearing preservation were evident with utilization of protons [59]. Current randomized control trials are underway to elucidate the benefits of particle therapy using protons, neutrons, or carbon ions in grade 4 astrocytomas, which may prove beneficial in eloquent locations like the CPA [15,60].…”

“…58 Current randomized control trials are underway to elucidate the benefits of particle therapy using protons, neutrons, or carbon ions in grade 4 astrocytomas, which may prove beneficial in eloquent locations like the CPA. 15,59 Finally, stereotactic radiosurgery (SRS) represents a treatment modality commonly utilized for benign CPA tumors yet reserved only as salvage therapy for treatment of locally recurrent high-grade astrocytomas. 15,54,[60][61][62] An optimal SRS technique and regimen remains investigational for high-grade astrocytomas despite anatomic location, and may still prove of limited use in the posterior fossa due to its increased toxicity and rates of radiation necrosis as compared with the conventional radiotherapy.…”

“… 58 Current randomized control trials are underway to elucidate the benefits of particle therapy using protons, neutrons, or carbon ions in grade 4 astrocytomas, which may prove beneficial in eloquent locations like the CPA. 15 59 …”

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches

“…[75,76] IMRT allows for the delivery of higher radiation doses to the tumor while sparing normal tissues, thereby reducing the risk of radiation-related toxicity. [77] SRS involves the delivery of a high dose of radiation to the tumor in a single fraction, using a highly precise targeting system. [78] The outcomes of advanced radiotherapy techniques in GBM have been promising, with some studies showing improved tumor control and survival outcomes compared to conventional radiotherapy techniques.…”

Analysis of safety and efficacy of proton radiotherapy for IDH-mutated glioma WHO grade 2 and 3

“…The fact that protons spare surrounding healthy tissue may also contribute to lower rates of endocrinopathy [ 22 ] and leucopenia which is an important criterion for patient chemotherapy eligibility [ 23 ]. The potential benefit of less leucopenia and therefore better chemotherapy protocol adherence is currently under evaluation for glioma WHO grade 2–3 in the GLIoProPH trial (University Hospital Essen, Germany, not yet registered on ClinicalTrials.gov) and for glioblastoma in the currently recruiting randomized prospective GRIPS trial (University Hospital Heidelberg, Germany) [ 24 ].…”