Background Tumor mutation burden (TMB) has been validated as a predictive biomarker for immunotherapy response and survival in numerous cancer types. Limited data is available on the inherent prognostic role of TMB in early-stage tumors. Objective To evaluate the prognostic role of TMB in early-stage, resected non-small cell lung cancer (NSCLC). Design Systematic review and meta-analysis of pertinent prospective and retrospective studies. Data sources and methods Publication search was performed in PubMed, Embase, Cochrane Library, and Web of Science databases. Based on the level of heterogeneity, a random- or fixed-effects model was used to calculate pooled effects of hazard ratio (HR) for overall survival (OS) and disease-free survival (DFS). The source of heterogeneity was investigated using sensitivity analysis, subgroup analysis, and publication bias assessment. Results Ten studies comprising 2520 patients were included in this analysis. There was no statistically significant difference in OS (HR, 1.18, 95% CI, 0.70, 1.33; p 0.53, I2 = 80%; phet < 0.0001) and DFS (HR, 1.18, 95% CI, 0.91, 1.52; p = 0.53, I2 = 75%; phet = 0.0001) between the high-TMB and low-TMB group. Subgroup analyses indicated that East Asian ethnicity, and TMB detected using whole exome sequencing, and studies with <100 patients had poor DFS in the high-TMB group. Conclusion The inherent prognostic role of TMB is limited in early-stage NSCLC. Ethnic differences in mutation burden must be considered while designing future trials on neoadjuvant immunotherapy. Further research in the harmonization and standardization of panel-based TMB is essential for its widespread clinical utility.Registration: CRD42023392846.

中文翻译：

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TMB 在早期非小细胞肺癌中的预后价值：系统评价和荟萃分析。

背景 肿瘤突变负荷 (TMB) 已被验证为多种癌症类型免疫治疗反应和生存的预测生物标志物。关于 TMB 在早期肿瘤中固有的预后作用的数据有限。目的 评估 TMB 在早期已切除非小细胞肺癌 (NSCLC) 中的预后作用。设计相关前瞻性和回顾性研究的系统回顾和荟萃分析。数据来源和方法 在 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中进行出版物检索。根据异质性水平，使用随机或固定效应模型来计算风险比 (HR) 对总生存 (OS) 和无病生存 (DFS) 的汇总效应。使用敏感性分析、亚组分析和发表偏倚评估来调查异质性的来源。结果 本分析纳入了 10 项研究，涉及 2520 名患者。OS（HR，1.18，95% CI，0.70，1.33；p = 0.53，I2 = 80%；phet < 0.0001）和 DFS（HR，1.18，95% CI，0.91，1.52；p = 0.53，I2 = 75%；phet = 0.0001）在高 TMB 组和低 TMB 组之间。亚组分析表明东亚种族和使用全外显子组测序检测到的 TMB，并且对 <100 名患者进行的研究在高 TMB 组中 DFS 较差。结论 TMB 在早期 NSCLC 中的固有预后作用有限。在设计未来的新辅助免疫治疗试验时，必须考虑突变负担的种族差异。基于面板的 TMB 的协调和标准化的进一步研究对其广泛的临床应用至关重要。注册：CRD42023392846。