Strategies for Managing Postradiotherapy Cerebral Radiation Necrosis in Nontarget Brain Tissue

Cerebral radiation necrosis (CRN) is a relatively common but poorly understood radiation dose-limiting complication of radiotherapy, involving brain tissue necrosis emerging after radiotherapy for brain tumors or head and neck cancers. Risks vary with radiotherapy modality, dose, treatment volumes, and fractionation schedules, and possibly, concurrent chemotherapy — but the molecular pathogenesis of this condition remains unclear. CRN represents a challenge to patient cognitive performance and quality of life, but surgical interventions can slow or halt CRN progression and palliate its clinical symptoms. Low-dose bevacizumab appears to play a promising role in CRN management.

Cerebral radiation necrosis was first recognized more than 50 years ago but remains an incompletely understood dose-limiting complication of radiotherapy. CRN involves necrosis of nontarget, healthy brain tissue following intracranial or regional radiotherapy for primary or metastatic brain tumors or head and neck cancers.^1,2 CRN typically occurs 6 months or more after treatment but can sometimes emerge much earlier.

Early detection and treatment are important because of the potentially profound effects on patients’ quality of life, including neuropsychiatric sequelae.³ CRN can also be fatal due to cerebral edema-associated elevated intracranial pressure and herniation or cerebral hemorrhage.^3-6

No clinical definitive guidelines exist for its treatment but surgery and corticosteroids can slow or halt CRN progression and several other treatment strategies are undergoing development, including low-dose bevacizumab, pentoxifylline, and hyperbaric oxygen therapy.^4-7 Minimally invasive laser interstitial thermal ablation is also under study.⁶ Treatments have not yet been compared in prospective, head-to-head clinical trials, however.

Despite advances in molecular pathology of CRN, its physiological underpinnings are still not entirely understood, but among patients with lung cancer and brain metastasis, oncogenic driver EGFR or ALK mutations and treatment with tyrosine kinase inhibitors appear to increase CRN risk.^1,2,4,5 Inflammatory cytokine pathways and edema are believed to be involved in CRN progression. Radiation modality, dose, treatment volumes, and fractionation schedules appear to be modulating factors, as might immunotherapy or concurrent chemotherapy, although the latter associations remain controversial.^1,2,4,5