This article gives a brief historical overview of the development of standard management for high-grade gliomas (HGGs). The current standard of care, trimodality therapy with maximal safe resection followed by involved-field radiotherapy (RT) with concomitant/adjuvant temozolomide, confers median survival of 14.6 months, and a modest but measurable proportion (9.8%) of patients survives 5 or more years. We review the toxicities associated with irradiation of the central nervous system for patients with HGG, with focus on the pathophysiology, clinical manifestations, and potential preventative strategies for long-term neurocognitive dysfunction, which remains a pervasive, progressive, and clinically devastating sequela of trimodality therapy. Treatment of cognitive decline after RT is limited, and strategies for preventing this complication are being investigated.
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