Preoperative Proton Irradiation for High-grade Brain Gliomas.

The goal of this clinical trial is to learn if preopearative proton therapy (PPT) is tolerable in patients with High-grade brain gliomas. It will also learn about the influence on surgical procedure, clinical effects and safety of regular treatment. The main questions it aims to answer are: Does preoprative proton therapy well-tolerated? What maximal dose of PPT is safe? Proposed Treatment Stages 1. Multidisciplinary board (neurosurgeon, radiation therapist, and medical oncologist) decision of patient enrollment. 2. Course of preoperative proton stereotactic radiotherapy (PSRT) directed at the tumor only: GTV=contrast-part of brain giloma, CTV=GTV. Dose regimens: first 3 patients - 4 Gy(RBE) × 5 fractions; subsequent 3 patients - 5 Gy(RBE) × 5 fractions; subsequent 3 patients - 6 Gy(RBE) × 5 fractions. RBE = Relative biological efficacy, equal 1.1 for protons. Should any information regarding unacceptable treatment toxicity emerge, the study will be terminated. 3. Microsurgical resection of the contrast-enhancing portion of the tumor using fluorescence microscopy and, when indicated, neurophysiological monitoring. 4. Contrast-enhanced MRI to assess the resection volume within the first 24-48 hours after surgery. 5. Follow-up evaluation - clinical, morphological, and radiological assessment of the effects of the preoperative and surgical treatment stages, performed 3-4 weeks after the surgical phase. 6. Standard treatment and follow-up: Chemoradiotherapy with a scanned proton beam combined with temozolomide 75 mg/m², given at 2 Gy × 30 fractions, to commence 4-6 weeks after surgery. Adjuvant chemotherapy with temozolomide 150-200 mg/m² on a 5/23 schedule (maintenance chemotherapy), for 12 cycles or until disease progression/unacceptable toxicity. 7. Follow-up - control examinations every 1 month after completion of chemoradiotherapy, then every 3 months for the first year.