Introduction: Tumor mutation burden (TMB) is thought to be associated with the amount of neoantigen in the tumor and to have an important role in predicting the effect of immune checkpoint inhibitors. However, the relevance of TMB to prognosis is not yet fully understood. In this study, we investigated the clinical significance of TMB in patients with NSCLC and examined the relationship between TMB and prognosis. Methods: We calculated TMB within individual tumors by whole‐exome sequencing analysis using next‐generation sequencing. We included that there were 90 patients with NSCLC who underwent surgery in the Hospital of Fukushima Medical University from 2013 to 2016. No patients received chemotherapy or immunotherapy before surgery. We assessed the correlation between TMB and prognosis. Results: TMB greater than 62 was associated with worse overall survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003). Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p = 0.019). In patients with stage I NSCLC, higher TMB was associated with worse prognosis for both OS (HR = 7.582, p = 0.0018) and disease‐free survival (HR = 6.07, p = 0.0072). Conclusions: High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS.

中文翻译：

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肿瘤突变负荷对完全切除的非小细胞肺癌患者的预后影响：简要报告

简介：肿瘤突变负荷（TMB）被认为与肿瘤中新抗原的数量有关，并且在预测免疫检查点抑制剂的效果方面具有重要作用。然而，TMB 与预后的相关性尚不完全清楚。在本研究中，我们调查了 TMB 在 NSCLC 患者中的临床意义，并检查了 TMB 与预后之间的关系。方法：我们使用新一代测序通过全外显子组测序分析计算单个肿瘤内的 TMB。我们纳入了2013年至2016年在福岛医科大学医院接受手术的90例NSCLC患者。没有患者在手术前接受过化疗或免疫治疗。我们评估了 TMB 与预后之间的相关性。结果：TMB 大于 62 与 NSCLC 患者的总生存期 (OS) 较差相关（风险比 [HR] = 6.633，p = 0.0003）。多变量分析显示高 TMB 预后不良（HR = 12.31，p = 0.019）。在 I 期 NSCLC 患者中，较高的 TMB 与较差的 OS（HR = 7.582，p = 0.0018）和无病生存（HR = 6.07，p = 0.0072）预后相关。结论：NSCLC中高TMB是不良预后因素。如果高 TMB 是免疫检查点抑制剂疗效的预测指标，则免疫检查点抑制剂的术后辅助治疗可能有助于改善复发和 OS。较高的 TMB 与 OS（HR = 7.582，p = 0.0018）和无病生存（HR = 6.07，p = 0.0072）的预后较差相关。结论：NSCLC中高TMB是不良预后因素。如果高 TMB 是免疫检查点抑制剂疗效的预测指标，则免疫检查点抑制剂的术后辅助治疗可能有助于改善复发和 OS。较高的 TMB 与 OS（HR = 7.582，p = 0.0018）和无病生存（HR = 6.07，p = 0.0072）的预后较差相关。结论：NSCLC中高TMB是不良预后因素。如果高 TMB 是免疫检查点抑制剂疗效的预测指标，则免疫检查点抑制剂的术后辅助治疗可能有助于改善复发和 OS。