Urias Eduardo, Lee Jaehoon, Weil Christopher R, Roach Eric, Lloyd Shane, Hashibe Mia, Facciabene Andrea, Maity Amit, Tao Randa
Department of Radiation Oncology, University of Utah Health Huntsman Cancer Institute, Salt Lake City, Utah, USA.
Department of Educational Psychology, Leadership, and Counseling, Texas Tech University, Lubbock, Texas, USA.
BMJ Oncol. 2025 May 7;4(1):e000732. doi: 10.1136/bmjonc-2025-000732. eCollection 2025.
To pool data from prospective clinical trials investigating combined stereotactic ablative radiotherapy (SABR) with immune checkpoint inhibitors (ICI) in patients with metastatic cancers.
PubMed, Scopus and EMBASE were queried for full-length articles of prospective clinical trials involving patients with metastatic solid tumours. Random-effects meta-analysis was performed with the Knapp-Hartung method. Multilevel regression analyses with primary cancers used as random effects and pairwise comparisons with two-tailed test adjusted with Benjamini-Hochberg method were performed. Regression coefficients (β) were calculated to assess the correlation between dose and outcomes.
We identified 30 trials and 35 individual treatment arms with a total of 951 patients with at least one outcome metric reported. Large heterogeneity was identified for all outcomes measured (I range: 75%-86%). The pooled rate of grade 3+ treatment-related adverse events was 18% (95% CI 11% to 24%). The progression-free survival (PFS) and overall survival (OS) at 6 months were 27% (95% CI 19% to 36%) and 67% (95% CI 59% to 76%), respectively. On multilevel regression, we identified improvement in 6-month PFS (β=0.6, p=0.003) and OS (β=1.6, p=0.04) with increasing BED10Gy doses. Combined-target ICI correlated with better 6-month OS when compared with αPD-1/PD-L1 alone.
We report a safety profile of combined ICI with SABR in patients with metastatic cancer that is comparable to that of ICI alone. We identified higher doses of radiotherapy and dual-target ICI to be associated with better OS at 6 months. Large heterogeneity and the lack of a control group limit the interpretation of our findings.
汇总前瞻性临床试验的数据，这些试验研究了立体定向消融放疗（SABR）联合免疫检查点抑制剂（ICI）用于转移性癌症患者的情况。
检索PubMed、Scopus和EMBASE，查找涉及转移性实体瘤患者的前瞻性临床试验的全文文章。采用Knapp-Hartung方法进行随机效应荟萃分析。进行以原发性癌症为随机效应的多水平回归分析，并采用Benjamini-Hochberg方法调整的双尾检验进行两两比较。计算回归系数（β）以评估剂量与结局之间的相关性。
我们确定了30项试验和35个单独的治疗组，共有951例患者报告了至少一项结局指标。在所测量的所有结局中均发现了较大的异质性（I范围：75%-86%）。3级及以上治疗相关不良事件的汇总发生率为18%（95%CI 11%至24%）。6个月时的无进展生存期（PFS）和总生存期（OS）分别为27%（95%CI 19%至36%）和67%（95%CI 59%至76%）。在多水平回归分析中，我们发现随着BED10Gy剂量的增加，6个月时的PFS（β=0.6，p=0.003）和OS（β=1.6，p=0.04）有所改善。与单独使用αPD-1/PD-L1相比，联合靶向ICI与更好的6个月OS相关。
我们报告了ICI联合SABR用于转移性癌症患者的安全性概况，与单独使用ICI相当。我们发现更高剂量的放疗和双靶向ICI与6个月时更好的OS相关。较大的异质性和缺乏对照组限制了我们研究结果的解释。
