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接受抗PD-1治疗的食管鳞状细胞癌患者的联合免疫预后指数

A combined immune prognostic index in esophageal squamous cell carcinoma patients treated with anti-PD-1 therapy.

作者信息

Ji Shoujian, Zhao Chuanhua, Liu Rongrui, Wang Yan, Yang Qing, Yang Hua, Xu Jianming

机构信息

Department of Gastroenterology, The 960 Hospital of the PLA, Jinan, China.

Department of Gastrointestinal Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China.

出版信息

Ther Adv Med Oncol. 2023 Jun 12;15:17588359231174869. doi: 10.1177/17588359231174869. eCollection 2023.

Abstract

BACKGROUND

Only a fraction of patients with esophageal squamous cell carcinoma (ESCC) show tumor responses to anti-programmed cell death protein 1 (PD-1) therapy. The predictive value of single biomarkers for prognosis is limited, and a more comprehensive approach that incorporates multiple factors may improve the prognostic prediction. Here, we conducted a retrospective study to develop a combined immune prognostic index (CIPI) for predicting clinical outcomes of ESCC patients treated with anti-PD-1 therapy.

DESIGN AND METHODS

We performed a pooled analysis of two multicenter clinical trials comparing immunotherapy chemotherapy as second-line treatment in ESCC patients. The discovery cohort comprised patients who received anti-PD-1 inhibitors ( = 322) and the control cohort comprised patients who received chemotherapy ( = 307). The validation cohort included patients with pan-cancers treated with PD-1/programmed cell death ligand-1 inhibitors, except for ESCC ( = 110). Multivariable Cox proportional hazard regression was used to assess the prediction value of variables on survival.

RESULTS

In the discovery cohort, neutrophil-to-lymphocyte ratio, serum albumin, and liver metastasis were independently associated with overall survival (OS) and progression-free survival (PFS). We integrated the three variables into CIPI and found that CIPI could categorize patients into four subgroups (CIPI 0 to CIPI 3) with distinct OS, PFS, and tumor responses. The CIPI was also predictive of clinical outcomes in the validation cohort, but not in the control cohort. Furthermore, patients with CIPI 0, CIPI 1, and CIPI 2 were more likely to benefit from anti-PD-1 monotherapy than chemotherapy, while patients with CIPI 3 did not benefit from anti-PD-1 monotherapy over chemotherapy.

CONCLUSIONS

The CIPI score was a robust biomarker for prognostic prediction in ESCC patients treated with anti-PD-1 therapy and was immunotherapy specific. The CIPI score may also be applicable for prognostic prediction in pan-cancers.

摘要

背景

只有一小部分食管鳞状细胞癌(ESCC)患者对抗程序性细胞死亡蛋白1(PD-1)治疗有肿瘤反应。单一生物标志物对预后的预测价值有限,采用包含多种因素的更全面方法可能会改善预后预测。在此,我们进行了一项回顾性研究,以开发一种联合免疫预后指数(CIPI)来预测接受抗PD-1治疗的ESCC患者的临床结局。

设计与方法

我们对两项多中心临床试验进行了汇总分析,比较免疫疗法与化疗作为ESCC患者的二线治疗。发现队列包括接受抗PD-1抑制剂的患者(n = 322),对照队列包括接受化疗的患者(n = 307)。验证队列包括接受PD-1/程序性细胞死亡配体1抑制剂治疗的泛癌患者,但不包括ESCC患者(n = 110)。采用多变量Cox比例风险回归评估变量对生存的预测价值。

结果

在发现队列中,中性粒细胞与淋巴细胞比值、血清白蛋白和肝转移与总生存期(OS)和无进展生存期(PFS)独立相关。我们将这三个变量整合到CIPI中,发现CIPI可将患者分为四个亚组(CIPI 0至CIPI 3),其OS、PFS和肿瘤反应各不相同。CIPI在验证队列中也可预测临床结局,但在对照队列中则不然。此外,CIPI 0、CIPI 1和CIPI 2的患者比化疗更有可能从抗PD-1单药治疗中获益,而CIPI 3的患者从抗PD-1单药治疗中并未比化疗获益更多。

结论

CIPI评分是接受抗PD-1治疗的ESCC患者预后预测的可靠生物标志物,且具有免疫疗法特异性。CIPI评分也可能适用于泛癌的预后预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/833e/10272641/6f84f2195bd4/10.1177_17588359231174869-fig1.jpg

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