Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy
Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy
复制标题
循环血清淀粉样蛋白 A (SAA) 的基线和早期变化可预测接受抗 PD-1/PD-L1 单药治疗的晚期非小细胞肺癌患者的生存结果
DOI：
10.1016/j.lungcan.2021.05.030
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发表时间：
2021-06-01
期刊：
影响因子：
5.3
通讯作者：
Hong, Shaodong
中科院分区：
文献类型：
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作者：
He, Li-Na;Fu, Sha;Hong, Shaodong
背景：全身炎症在肿瘤发生中起着重要作用，并与不同癌症类型患者的总体生存有关，包括接受免疫检查点阻断(ICB)治疗的患者。血清淀粉样蛋白A(SAA)是一种急性时相蛋白，是持续性炎症的标志物。我们假设循环SAA可以预测接受PD-1/PDL1 ICB治疗的晚期非小细胞肺癌(ANSCLC)患者的预后。材料和方法：对2016年8月至2018年6月在中山大学肿瘤中心(广州，中国)接受抗PD-(L)1单药治疗的91例非小细胞肺癌患者进行回顾性研究。我们检查了基线和8(+/-2)周后循环SAA对总存活率(OS)的影响。使用X-Tile程序确定截断值，从而优化Kaplan Meier生存曲线分裂的意义。生存分析采用Kaplan-Meier方法和Cox回归分析。结果：在单因素分析中，基线SAA值为137.6 mg/L是OS分层的最佳临界值，高SAA值(危险比为2.76，95%可信区间为1.47~5.18；P=0.002)和早期SAA值下降(HR为1.5 1；95%CI为1.11~2.06；P=0.009)均与OS不良有关。在多因素分析中，性别、吸烟状况、运动状态、肝转移、中性粒细胞/淋巴细胞比率、基线SAA和SAA早期变化是独立预测OS的因素(均P<；0.05)。基线SAA和GT；=137.6毫克/L和没有早期SAA下降的联合队列确定了一小部分OS显著恶化的队列(中位数3.2月)。结论：在接受PD-1/PD-L1 ICB治疗的非小细胞肺癌患者中，高基线和没有早期循环SAA下降与不良预后显著相关。将这两个SAA指数结合起来，可改善风险分层。这一简单、易得和经济有效的生物标志物的预后价值需要更大的前瞻性验证，然后才能做出明确的建议。
Background: Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent infla mmation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PDL1 ICB. Materials and Methods: This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (+/- 2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between KaplanMeier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses. Results: The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-tolymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P < 0.05). A combined baseline SAA >= 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months). Conclusions: Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.