Wankhede Durgesh, Grover Sandeep, Hofman Paul
German Cancer Research Center, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.
Center for Human Genetics, Universitatsklinikum Giessen und Marburg - Standort Marburg, Marburg, Germany.
Ther Adv Med Oncol. 2023 Aug 31;15:17588359231195199. doi: 10.1177/17588359231195199. eCollection 2023.
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.
To evaluate the prognostic role of TMB in early-stage, resected non-small cell lung cancer (NSCLC).
Systematic review and meta-analysis of pertinent prospective and retrospective studies.
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.
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; 0.53, = 80%; < 0.0001) and DFS (HR, 1.18, 95% CI, 0.91, 1.52; = 0.53, = 75%; = 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.
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. CRD42023392846.
肿瘤突变负荷（TMB）已被证实是多种癌症类型中免疫治疗反应和生存的预测生物标志物。关于TMB在早期肿瘤中的固有预后作用的数据有限。
评估TMB在早期、可切除的非小细胞肺癌（NSCLC）中的预后作用。
对相关前瞻性和回顾性研究进行系统评价和荟萃分析。
在PubMed、Embase、Cochrane图书馆和Web of Science数据库中进行文献检索。根据异质性水平，使用随机或固定效应模型计算总生存（OS）和无病生存（DFS）的风险比（HR）的合并效应。使用敏感性分析、亚组分析和发表偏倚评估来研究异质性来源。
本分析纳入了10项研究，共2520例患者。高TMB组和低TMB组在OS（HR，1.18，95%CI，0.70，1.33；I² = 80%；P < 0.0001）和DFS（HR，1.18，95%CI，0.91，1.52；I² = 53%；P = 0.0001）方面无统计学显著差异。亚组分析表明，在高TMB组中，东亚种族、使用全外显子测序检测的TMB以及患者少于100例的研究DFS较差。
TMB在早期NSCLC中的固有预后作用有限。在设计未来新辅助免疫治疗试验时，必须考虑突变负荷的种族差异。基于panel的TMB的协调和标准化的进一步研究对于其广泛的临床应用至关重要。CRD42023392846。
