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胃食管结合部/胃癌转移性患者接受 PD-1/PD-L1 免疫检查点抑制剂治疗的胃炎症预后指数(GIPI)。

Gastric Inflammatory Prognostic Index (GIPI) in Patients with Metastatic Gastro-Esophageal Junction/Gastric Cancer Treated with PD-1/PD-L1 Immune Checkpoint Inhibitors.

机构信息

Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford, 81, 00133, Rome, Italy.

Medical Oncology, Sarah Cannon Research Institute UK, London, UK.

出版信息

Target Oncol. 2020 Jun;15(3):327-336. doi: 10.1007/s11523-020-00723-z.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC.

OBJECTIVE

Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC.

METHODS

Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram.

RESULTS

Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL (n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor (n = 28) (HR 2.48; p = 0.0015).

CONCLUSIONS

GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials.

摘要

背景

免疫检查点抑制剂(ICIs)在未经选择的转移性胃食管交界处(mGOJ)/胃癌(GC)大量预处理患者中显示出改善的总生存期(OS)。基于程序性死亡配体 1(PD-L1)表达选择患者的尝试似乎并不理想。强有力的理由表明,对于接受 mGOJ/GC 的 ICI 治疗的患者,炎症生物标志物具有预后作用。

目的

我们的目的是评估炎症标志物是否与接受 mGOJ/GC 的 ICI 治疗患者的生存相关。

方法

回顾性分析了 57 例 mGOJ/GC 患者的基线时的 10 种炎症标志物,这些患者的 PD-L1 状态未知,接受二线 ICI 治疗,并与 OS 相关。然后在多变量 Cox 回归模型中分析选定的变量,并用于构建 GIPI 列线图。

结果

中性粒细胞/淋巴细胞比值(NLR)和 C 反应蛋白(CRP)作为连续变量和白蛋白分类为小于或大于 30 g/dL 是 OS 的最显著预测因素,并用于构建 GIPI 列线图。基于列线图的最低、中低、中高和最高风险四分位数与中位 OS(mOS)分别为 14.9、7.1、5.6 和 2.1 个月相关(最高 vs. 最低风险的 HR 为 4.94;p=0.0002)。通过最佳地二分类 CRP 和 NLR,一个或多个危险因素 NLR>6、CRP>15mg/L 和白蛋白<30g/dL(n=29)的患者的 mOS 为 3.9 个月,而无危险因素(n=28)的患者 mOS 为 14.2 个月(HR 2.48;p=0.0015)。

结论

GIPI,结合 NLR、CRP 和白蛋白,是第一个在接受 ICI 治疗的 mGOJ/GC 患者中具有显著预后价值的炎症指标。GIPI 需要在独立队列和前瞻性临床试验中进行验证。

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