中性粒细胞与淋巴细胞比值与晚期胆道系统恶性肿瘤免疫检查点抑制剂治疗疗效及预后的关系

Association of neutrophil-to-lymphocyte ratio with survival outcomes in advanced bile tract carcinoma patients treated with PD-1 inhibitors

  • 摘要:
      背景  免疫检查点抑制剂(immune checkpoint inhibitor,ICIs)在晚期胆道系统恶性肿瘤(bile tract carcinoma, BTC)患者中的应用逐渐增多,但仅有部分患者获益,且存在免疫相关不良反应等风险,寻找有效的免疫疗效相关预测指标可更早地筛选出获益人群。
      目的  探讨中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)与晚期胆道恶性肿瘤免疫治疗疗效及预后的关系。
      方法  纳入2015年9月- 2021年4月于解放军总医院第一医学中心和第五医学中心初次接受ICIs治疗的晚期BTC患者106例。通过基线NLR预测疾病控制状态的ROC曲线以获取NLR最佳Cut-off值,根据是否大于NLR最佳Cut-off值将患者分为NLR高水平组和NLR低水平组。采用Kaplan-Meier进行单因素分析,Cox回归进行多因素分析。
      结果  BTC患者,中位年龄59岁,女性44例,男性62例。NLR的最佳Cut-off值为2.54。与NLR低水平组比较,NLR高水平组有更高概率出现疾病进展(OR=4.365,95% CI:1.849 ~ 10.302,P=0.001)。NLR高水平组和NLR低水平组的中位总生存(overall survival,OS)率分别为33.9个月和8.7个月,中位无进展生存(progression-free survival,PFS)率分别为10.7个月和4.6个月,差异均有统计学意义(P均<0.05)。多因素分析结果显示NLR是OS和PFS的有效预测指标。
      结论  基线NLR为晚期 BTC免疫治疗预后的独立影响因素。基线NLR高水平患者可能较难从免疫治疗中获益。

     

    Abstract:
      Background   The application of immune checkpoint inhibitors (ICIs) is gradually increasing in advanced bile tract carcinoma (BTC), but only some patients have benefited from it. Immunosuppressants are not only costly, but also have risks of immune-related adverse reactions. Looking for effective predictors of immune efficacy can screen the benefiting group earlier.
      Objective   To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and the disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) of advanced BTC with ICIs.
      Methods   Totally 106 advanced BTC patients who received ICIs treatment for the first time from September 2015 to April 2021 in the First and Fifth Medical Center of Chinese PLA General Hospital were included in this study. The optimal cut-off value of NLR was obtained by ROC curve according to the disease control status. Patients were divided into high-level group and low-level group based on cut-off value of NLR. Kaplan-Meier was used for univariate analysis, and Cox for multivariate analysis.
      Results  The median age of the 106 enrolled advanced BTC patients was 59 years old, and 44 patients were female, and 62 patients were male. Compared to the NLR low level group, patients in the high level group had higher rate of disease progression (OR=4.365, 95% CI: 1.849-10.302, P=0.001). The median OS was 33.9 months in the NLR low level group, and 8.7 months in the high level group, and the median PFS was 10.7 months in the NLR low level group, and 4.6 months in the high level group, with significant difference (all P<0.05). The results of multivariate analysis showed that LDH was an effective predictor of OS and PFS.
      Conclusion  Baseline NLR are independent factors influencing the prognosis of advanced BTC immunotherapy. Advanced BTC patients with high level of baseline NLR may be difficult to benefit from ICIs.

     

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