Symptomatic radiation necrosis following intracranial brachytherapy: a systematic review and meta-analysis

To estimate the pooled incidence of symptomatic radiation necrosis (RN) following intracranial brachytherapy and explore associations between clinical and technical variables and RN risk.

PubMed, Embase, Web of Science, and the Cochrane Library were searched from 1954 - 2024 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible human studies reported symptomatic RN after intracranial brachytherapy. RN ascertainment was secondarily classified as clear, partial, or unclear based on reproducibility of diagnostic criteria. A random-effects generalized linear mixed model was used to pool incidence rates, with subgroup analyses by tumor type, implant technique, isotope, dose rate, and prior radiation. Study quality was assessed using National Institutes of Health tools.

Eighty-three studies encompassing 3,666 patients were included. The pooled incidence of symptomatic RN was 5.67% (95% CI: 3.84%-8.29%; I² = 75.7%). RN ascertainment was clear in 25 studies, partial in 43, and unclear in 15. In sensitivity analyses, pooled symptomatic RN incidence was 8.71% among studies with clear RN definitions and 7.48% among studies with clear or partial definitions. Subgroup RN rates were 3.72% for low-grade gliomas, 8.44% for high-grade gliomas, 2.07% for brain metastases, and 8.98% for meningiomas. Isotope-specific rates were 5.83% for Iodine-125, 7.61% for Iridium-192, and 2.07% for Cesium-131. No statistically significant subgroup differences were observed.

Symptomatic RN occurs in approximately 5.7% of patients following intracranial brachytherapy, within the range reported for other focal radiation therapies. Subgroup findings were not statistically significant and should be interpreted in the context of clinical and methodological heterogeneity.