PD-1/PD-L1抑制剂与立体定向放射外科治疗脑转移瘤：一项系统评价和荟萃分析。
完整摘要 · 中文译文
目的：立体定向放射外科（SRS）是局限性脑转移瘤（BM）的首选治疗方法，其与PD-1/PD-L1抑制剂的联合应用被认为可产生协同治疗获益。然而，关于放射诱导的脑坏死（RIBN）风险增加存在担忧。本系统综述和荟萃分析评估了PD-1/PD-L1抑制剂联合SRS或分次立体定向放疗（FSRT）的疗效和毒性特征。 方法：筛选了四个数据库，即Embase、Web of Science、PubMed和Scopus，时间范围从建库至2025年11月。主要结局为总生存期（OS）、颅外及远处颅内无进展生存期（PFS）以及局部控制率（LC）。根据原发转移灶来源和放疗方式进行了亚组分析。我们提取了RIBN事件和≥3级神经系统事件。采用随机效应模型进行单臂荟萃分析。本综述方案于2025年11月在PROSPERO注册（ID CRD420251171879）。 结果：共纳入34项研究，发表于2016年至2025年间，包含2,587例脑转移瘤患者。汇总的一年OS为65%（95% CI 60-69）。非小细胞肺癌（NSCLC）脑转移患者的一年OS为68%，黑色素瘤脑转移患者的OS为61%。一年LC和远处颅内PFS分别为87%（95% CI 79-92）和40.23%（95% CI 17.99-62.47）。3级RIBN的累积发生率（CI）为5%（95% CI 3-8），≥3级神经系统事件发生率为7%（95% CI 4-13）。无统计学 在黑色素瘤与非小细胞肺癌原发肿瘤亚组之间，未发现RIBN发生率存在统计学显著差异。 结论：SRS/FSRT联合PD-1/PD-L1抑制剂与良好的颅内PFS和LC以及可耐受的毒性反应相关，3级RIBN发生率相对较低。这些发现支持在免疫治疗时代该联合模式的可行性。然而，关于RIBN增量风险的确定性结论仍需未来的前瞻性试验加以验证。
完整摘要 · 英文原文
PURPOSE: Stereotactic radiosurgery (SRS) is the treatment of choice for limited brain metastases (BM), and its combination with PD-1/PD-L1 inhibitors is hypothesized to offer synergistic therapeutic benefits. However, there are concerns regarding augmented risk of radiation-induced brain necrosis (RIBN). This systematic review and meta-analysis evaluate the efficacy and toxicity profile of PD-1/PD-L1 inhibitors combined with SRS or fractionated stereotactic radiotherapy (FSRT). METHODS: Four databases were screened, Embase, Web of Science, PubMed and Scopus from inception to November 2025. Primary outcomes were overall survival (OS), extracranial and distant intracranial progression free survival (PFS), and local control (LC). A subgroup analysis was performed based on the primary metastasis origin and radiotherapy treatment modalities. We extracted RIBN events and grade ≥ 3 neurological events. A single-arm meta-analysis was performed using the random-effects modeling. This review protocol was registered on November 2025 on PROSPERO (ID CRD420251171879). RESULTS: Thirty-four studies were included, published between 2016 and 2025 comprising 2,587 patients with BM. The pooled one-year OS was 65% (95% CI 60-69). Patients with BM from Non-Small Cell Lung Cancer (NSCLC) had one-year OS (68%) while melanoma BM had OS (61%). LC and distant intracranial PFS at one year were 87% (95% CI 79-92) and 40.23% (95% CI 17.99-62.47), respectively. The cumulative incidence (CI) of grade 3 RIBN was 5% (95% CI 3-8), and grade ≥ 3 neurological events occurred in 7% (95% CI 4-13). No statistically significant difference in RIBN rates was found between melanoma and NSCLC primaries subgroup. CONCLUSION: The combination of SRS/FSRT with PD-1/PD-L1 inhibitors is associated with favorable intracranial PFS and LC and a tolerable toxicity profile, with relatively lower rates of grade 3 RIBN. These findings support the feasibility of this combined modality in the immunotherapy era. However, definitive conclusions regarding the incremental risk of RIBN require future prospective trials.