A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab
A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab
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接受 atezolizumab 治疗的 NSCLC 患者血液肿瘤突变负荷与预后之间的非线性相关性
DOI：
10.1080/2162402x.2020.1731072
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发表时间：
2020-01-01
期刊：
影响因子：
7.2
通讯作者：
Han, Bao-Hui
中科院分区：
文献类型：
--
作者：
Nie, Wei;Qian, Jie;Han, Bao-Hui
在接受atezolizumab治疗的晚期非小细胞肺癌（NSCLC）中，观察到高血基肿瘤突变负担（bTMB）与改善的无进展生存期（PFS）之间的显著关联。然而，这一结果在最近的前瞻性研究中是不可重复的。我们假设bTMB和生存率之间可能存在非线性关联。本研究使用POPLAR （n = 105，训练集）和OAK （n = 324，验证集）试验的临床和遗传数据。采用限制性三次样条（RCS）评估bTMB与生存率之间的非线性关系。通过X-tile软件计算bTMB的截止值。在RCS图中，bTMB和PFS与总生存期（OS）呈非线性关系（P均非线性< 0.001）。bTMB预测PFS和OS的最佳临界值分别为7和14个突变/Mb。在训练组、验证组和联合组中，低、高bTMB患者的中位PFS和OS均明显长于中等bTMB患者。在程序性死亡配体1 （PD-L1）高表达人群中，低和高bTMB也与更长的PFS和OS相关。总之，在接受atezolizumab治疗的NSCLC患者中，bTMB与生存率之间存在正非线性关联。低bTMB患者也可以从免疫治疗中获益。
ABSTRACT A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both P non-linearity < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.