Interventional stereotactic radiotherapy (brachytherapy) for unresected brain metastases: Systematic review of outcome and toxicity

Background: Stereotactic brachytherapy (SBT) is an underutilized treatment for brain metastases. This systematic review evaluates SBT's clinical outcomes, toxicity, and procedural characteristics for intact brain metastases in radiation-naive and radiation-recurrent patients. Methods: A systematic review was conducted following PRISMA guidelines and the PICOS framework. Studies published until June 30, 2024, were identified through searches of PubMed, Scopus, Web of Science, and Cochrane databases. Retrospective studies and prospective trials were included. Key extracted data included patient characteristics, treatment protocols, local control (LC), distant-intracranial control (DIC), overall survival (OS), and procedure-related toxicity. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results: Eight retrospective single-center studies involving 427 patients and 456 metastases met inclusion criteria. Median patient age ranged from 47 to 60 years, with most having a Karnofsky Performance Status ≥ 70. SBT mostly demonstrated high 1-year LC rates (93.3 %–100 %) and a 1-year DIC from 52 % to 90 %. Median OS for radiation-naive patients ranged from 8 to 17 vs. 6–28.4 months for radio-recurrent patients, with RPA class 1 showing the best outcomes. Toxicity was minimal, with no reported fatal complications or significant late toxicity. Across all studies, I-125 seeds were utilized, with temporary implantation predominating, while permanent implantation involved higher doses, up to 150 Gy, and extended treatment durations. Postoperative morbidity within 30 days ranged from 0 % to 6.6 % across different studies. No G3/G4 acute toxicities were reported. Conclusions: SBT is a highly effective and safe option for treating intact brain metastases, particularly in patients with large or radiation-recurrent lesions.