脑转移瘤（BMs）是最常见的颅内肿瘤。在一些病例中，它们呈大块状，与预后较差和治疗方案更为复杂有关。研究指出，在BMs中应用分阶段放射外科治疗可以实现局部控制，并且副作用较小。然而，对于大脑转移瘤（LBMs；>2cm）的应用方法尚未达成方法上的共识。因此，作者的目标是确定两阶段伽马刀放射外科治疗（GKRS）对LBMs的疗效和安全性，以优化患者术后状况。我们在PubMed/MEDLINE、Scopus、Web of Science、Cochrane（OvidSP）和Google Scholar上进行了现有文献的系统综述，包括截至2022年12月14日发表的作品。非随机临床试验、病例系列和队列研究被纳入。我们使用非随机研究干预(ROBINS-I)和Joanna Briggs Institute工具来评估偏倚风险。采用随机效应模型的荟萃分析计算了均值差异和比率估计。异质性程度以I2统计量表示。进行了亚组分析。最后，我们使用Grading of Recommendations Assessment、Development和Evaluation (GRADE)评估来评估证据的确定性。满足资格标准的研究包括14项，涵盖了958例患者（队列、病例系列和非随机临床试验）。报告了两阶段GKRS后的均值总体体积减小为6.27cm3 (95% CI 5.67-6.88 cm3)，以及54.36% (95% CI 39.92%-68.79%)。计算了完全缓解率（44.63%; 95% CI 26.50%-64.31%）、神经病死率（16.19%; 95% CI 7.68%-30.98%）和全因死亡率（47.92%; 95% CI 28.04%-68.49%）的总体比率。整体证据的可靠性从很低到中等不等。两阶段GKRS是治疗LBMs的一种有效且安全的方法。然而，由于缺乏可用的文献和方法论上的不足，证据的可靠性很低，无法提供强有力的证据来推荐这种干预措施。因此，有必要进行更高质量的原始研究。

Brain metastases (BMs) are the most common intracranial tumors. In several cases, they present as large masses, which are related to a worse prognosis and more complex therapeutic alternatives. Staged radiosurgery is reported to achieve local control with minimal radiation-related adverse events in BMs. However, no methodological consensus has been achieved in its use for large brain metastases (LBMs; > 2 cm). Therefore, the authors aimed to determine the effectiveness and safety of 2-stage Gamma Knife radiosurgery (GKRS) for LBMs, in order to optimize patients' postoperative course.A systematic review of available literature was run in PubMed/MEDLINE, Scopus, Web of Science, Cochrane (OvidSP), and Google Scholar for works published up to December 14, 2022. Nonrandomized clinical trials, case series, and cohort studies were included. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) and Joanna Briggs Institute tools. Pooled mean difference and rates estimates were calculated by a random-effects model meta-analysis. The degree of heterogeneity was expressed using the I2 statistic. A subgroup analysis was performed. Ultimately, the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment.Fourteen studies met the eligibility criteria (cohorts, case series, and nonrandomized clinical trials), including 958 patients. A total pooled mean volume reduction of 6.27 cm3 (95% CI 5.67-6.88 cm3) and 54.36% (95% CI 39.92%-68.79%) after 2-stage GKRS was reported. Pooled rates of complete response (44.63%; 95% CI 26.50%-64.31%), neurological mortality (16.19%; 95% CI 7.68%-30.98%), and all-cause mortality (47.92%; 95% CI 28.04%-68.49%) were calculated. Overall certainty of evidence ranged from very low to moderate.Two-stage GKRS is an effective and safe approach for the treatment of LBMs. Nevertheless, the lack of available literature and the weak methodological approaches used determine a low to very low certainty of evidence and cannot provide robust evidence to recommend this intervention. Therefore, it is necessary to conduct higher-quality primary studies.