衍生中性粒细胞与淋巴细胞比率与晚期胃癌免疫检查点抑制剂治疗预后的关系

Association of derived neutrophil-to-lymphocyte ratio with survival outcomes in advanced gastric cancer patients treated with PD-1 inhibitors

  • 摘要:
      背景  程序性死亡受体配体 1(programmed cell death 1 ligand 1,PD-L1)和微卫星不稳性(microsatellite instability,MSI)的表达被认为能够有效评估晚期胃癌(advanced gastric cancer,AGC)患者免疫治疗预后。但目前仍没有公认且有效的生物标志物可以识别AGC免疫治疗的受益人群。
      目的  探讨衍生中性粒细胞与淋巴细胞比率(derived neutrophil‐to‐lymphocyte ratio,dNLR)与AGC免疫治疗预后的关系。
      方法  纳入2014年12月- 2018年11月解放军总医院肿瘤中心学部接受免疫治疗的123例AGC患者。根据国外大型临床研究选取dNLR=3为临界值,分析不同dNLR水平组AGC患者免疫治疗后的中位总生存(overall survival,OS)和中位无进展生存(progression-free survival,PFS)。采用Kaplan-Meier和Cox比例风险回归模型进行生存分析。
      结果  AGC患者中位年龄58岁,女性31例,男性92例。中位OS为9.4个月,中位PFS为3.8个月。dNLR高水平组中位PFS为4.6个月,dNLR低水平组为2.6个月(HR:1.952,95% CI:1.248 ~ 3.053,P=0.008)。dNLR高水平组OS为11.2个月,dNLR低水平组为4.8个月(HR:0.59,95% CI:1.691 ~ 4.188,P<0.001)。dNLR高、低水平组的客观缓解率(25.0% vs 24.2%,P=0.932)、疾病控制率(46.4% vs 48.4%,P=0.853)差异无统计学意义。
      结论  治疗前dNLR水平是独立预测AGC患者免疫治疗后PFS和OS的生物标志物。基线dNLR低水平组患者或许可以从免疫治疗中获益。

     

    Abstract:
      Background   At present, biomarkers such as prevailing programmed cell death 1 ligand 1 (PD-L1) expression and microsatellite instability (MSI ) have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC). However, there are still lack of effective biomarkers for recognizing the benefit group with AGC treatment.
      Objective   To explore the correlation between derived neutrophil‐to‐lymphocyte ratio (dNLR) and the prognosis of AGC patients with immune checkpoint inhibitors (ICIs).
      Methods   A total of 123 AGC patients receiving immunotherapy in the Department of Tumor Center, Chinese PLA General Hospital from December 2014 to November 2018 were enrolled. According to the major clinical research in foreign countries, 3 was selected as the cut-off value of dNLR. The difference in median OS and median PFS of AGC patients with different levels (low-level group and high-level group) of dNLR after immunotherapy was analyzed. Kaplan-Meier was used for univariate analysis, and Cox regression model was used for multivariate analysis.
      Results  Of the 123 AGC patients, there were 31 female patients and 92 male patients, with median age of 58 years old. The median OS was 9.4 months, and the median PFS was 3.8 months. Median PFS was 4.6 months in the dNLR high level group, and 2.6 months in the low level group (HR: 1.952, 95% CI: 1.248-3.053, P=0.008). The median OS was 11.2 months in the dNLR high level group, and 4.8 months in the low level group (HR: 0.59, 95% CI: 1.691-4.188, P<0.001). No significant difference was found in ORR (25% vs 24.2%, P=0.932) and DCR (46.4% vs 48.4%, P=0.853) between the high and low dNLR groups.
      Conclusion  Our research shows that the level of dNLR before treatment is an independent biomarker for predicting PFS and OS after immunotherapy in AGC patients. Patients in dNLR low level group may benefit from ICIs.

     

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