Research AppraisalSystematic Review

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

Journal of neuro-oncologyLeskinen, Sandra, Inzerillo, Sean, Coelho, Anthony et al.12 June 2026DOI

Clinical Snapshot

80CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationPatients receiving intracranial brachytherapy for brain tumours (low-grade gliomas, high-grade gliomas, brain metastases, meningiomas)
I — InterventionIntracranial brachytherapy using various isotopes (Iodine-125, Iridium-192, Cesium-131)
C — ComparatorNo specific comparator - observational studies examining incidence
O — OutcomesSymptomatic radiation necrosis (primary outcome)

Bottom Line

This comprehensive meta-analysis of 83 studies involving 3,666 patients provides the most robust estimate to date of symptomatic radiation necrosis risk following intracranial brachytherapy. The pooled incidence of 5.67% (95% CI: 3.84%-8.29%) falls within the range reported for other focal radiation therapies, supporting brachytherapy as a reasonable treatment option. However, clinicians should note the substantial heterogeneity between studies (I² = 75.7%) and inconsistent diagnostic criteria for radiation necrosis across the literature. While subgroup analyses suggested higher rates in high-grade gliomas (8.44%) and meningiomas (8.98%) compared to brain metastases (2.07%), these differences were not statistically significant. The findings support informed consent discussions but highlight the need for standardised radiation necrosis diagnostic criteria in future studies. Australian practitioners should consider these rates when counselling patients about brachytherapy risks, particularly given the availability of alternative treatments like stereotactic radiosurgery.

Evidence: Moderate

Key Findings

  • P Value: Not reported for primary outcome

  • Effect Size: 5.67% pooled incidence

  • Primary Outcome: Symptomatic radiation necrosis incidence

  • Nnt Or Sensitivity: Approximately 1 in 18 patients (5.67%) will develop symptomatic radiation necrosis following intracranial brachytherapy

  • Confidence Interval: 95% CI: 3.84%-8.29%

Clinical Application

Results applicable to current practice as brachytherapy techniques and isotopes studied remain in clinical use Relevant to Australian neuro-oncology practice where brachytherapy is available in major centres; TGA-approved isotopes included in analysis; useful for informed consent discussions Patients with brain tumours considering intracranial brachytherapy, particularly those with high-grade gliomas and meningiomas who showed higher RN rates

Abstract

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

References

  1. 1.Leskinen, S., Inzerillo, S., Coelho, A., Shah, H. A., Mittelman, L., Ben-Shalom, N., Boockvar, J. A., Langer, D., D'Amico, R. S., & Wernicke, A. G. (2026). Symptomatic radiation necrosis following intracranial brachytherapy: a systematic review and meta-analysis. Journal of Neuro-Oncology. https://doi.org/10.1016/j.clineuro.2019.02.010
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