Re-irradiation for recurrent high-grade glioma: current evidence and practical considerations

Re-irradiation is an increasingly important salvage option for patients with recurrent high-grade glioma and glioblastoma, but its use is complicated by limited prospective evidence, heterogeneous treatment approaches, and concern for cumulative toxicity to the brain and critical neurologic structures. Available studies suggest that carefully selected patients may achieve meaningful local control, symptom relief, and preservation of neurologic function, although a consistent overall survival benefit has not been demonstrated. Treatment decisions therefore require individualized assessment of performance status, neurologic function, disease volume and pattern, interval from prior radiation therapy, expected prognosis, alternative salvage options, and overlap with previously irradiated organs at risk. In this expert opinion, we summarize the contemporary evidence supporting brain re-irradiation and discuss available techniques; we also describe a practical, organ-at-risk-driven framework for patient selection, target delineation, fractionation, cumulative dose assessment, and integration of systemic therapy. Re-irradiation can be delivered safely in selected patients, but treatment intensity should remain closely aligned with anatomy, prognosis, therapeutic alternatives, and patient goals.