国际肿瘤学杂志

国际肿瘤学杂志 ›› 2026, Vol. 53 ›› Issue (5): 276-282.doi: 10.3760/cma.j.cn371439-20251019-00045

• 论著 • 上一篇    下一篇

食管鳞状细胞癌患者新辅助治疗后sPD-1变化与病理缓解相关性

顾磊1, 韩济华2, 田文泽3, 周武壁4, 辛勇5()   

  1. 1 南京医科大学附属淮安第一医院肿瘤放疗科， 南京 223022
    2 南京医科大学附属淮安第一医院肿瘤科， 南京 223022
    3 南京医科大学附属淮安第一医院胸外科， 南京 223022
    4 南京医科大学附属淮安第一医院病理科， 南京 223022
    5 徐州医科大学附属医院放射肿瘤科， 徐州 221004
  • 收稿日期:2025-10-19 出版日期:2026-05-08 发布日期:2026-05-06
  • 通讯作者: 辛勇，Email： deep369@163.com
  • 基金资助:
    淮安市自然科学研究计划(HAB202201)

Correlation between the changes in sPD-1 after neoadjuvant therapy in patients with esophageal squamous cell carcinoma and pathological response

Gu Lei1, Han Jihua2, Tian Wenze3, Zhou Wubi4, Xin Yong5()   

  1. 1 Department of Radiation Oncology， Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University， Nanjing 223022， China
    2 Department of Oncology， Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University， Nanjing 223022， China
    3 Department of Thoracic Surgery， Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University， Nanjing 223022， China
    4 Department of Pathology， Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University， Nanjing 223022， China
    5 Department of Radiation Oncology， Affiliated Hospital of Xuzhou Medical University， Xuzhou 221004， China
  • Received:2025-10-19 Online:2026-05-08 Published:2026-05-06
  • Supported by:
    Huai'an Natural Science Research Plan(HAB202201)

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摘要：

目的 探讨食管鳞状细胞癌（ESCC）患者新辅助卡瑞利珠单抗联合化疗过程中血清可溶性程序性死亡受体1（sPD-1）的动态变化与病理缓解的相关性，评价其作为疗效预测指标的可行性。方法 选取2019年1月至2021年12月在南京医科大学附属淮安第一医院接受新辅助卡瑞利珠单抗联合白蛋白紫杉醇及顺铂治疗的125例局部晚期ESCC患者为研究对象。于基线、治疗第1周期后、治疗第2周期后及术前检测血清sPD-1水平，根据早期sPD-1下降情况（≥30%与<30%）将患者分为下降组（n=45）和非下降组（n=80）。采用广义估计方程（GEE）模型分析sPD-1动态变化与患者病理完全缓解（pCR）、主要病理缓解（MPR）及无事件生存期（EFS）的关系；采用logistic回归模型分析患者病理缓解的影响因素；绘制Kaplan-Meier曲线分析下降组和非下降组患者的EFS并行log-rank检验；采用Cox比例风险回归模型评估患者EFS的影响因素。结果 125例患者均顺利完成新辅助治疗及手术，R0切除率100%，无围手术期死亡。下降组与非下降组的基线sPD-1水平分别为5.9（4.5，7.3）、5.7（4.3，7.6）ng/ml，差异无统计学意义（Z=0.52，P=0.472）；治疗第1周期后sPD-1水平分别为3.1（2.4，4.0）、4.8（3.7，6.5）ng/ml，差异有统计学意义（Z=19.26，P<0.001）；治疗第2周期后sPD-1水平分别为2.8（2.2，3.7）、4.5（3.4，6.0）ng/ml，差异有统计学意义（Z=22.13，P<0.001）；术前sPD-1水平分别为2.6（2.0，3.5）、4.2（3.3，5.7）ng/ml，差异有统计学意义（Z=21.84，P<0.001）；GEE分析显示，时间主效应及组别主效应均显著（χ2=112.40，P<0.001；χ2=7.63，P=0.006），且时间与组别间存在显著交互作用（χ2=9.18，P=0.027）。治疗第1周期后，下降组的患者pCR率为42.2%（19/45），显著高于非下降组的19.5%（16/80）（χ2=7.59，P=0.006）。下降组的MPR率为68.9%（31/45），显著高于非下降组的48.1%（38/80）（χ2=5.35，P=0.021）。生存分析显示，下降组患者的中位EFS为34个月，长于非下降组的28个月（χ2=8.33，P=0.004）。多因素分析显示，早期sPD-1下降≥30%（OR=2.34，95%CI为1.18~4.63，P=0.015）和基线sPD-1（OR=0.89，95%CI为0.80~0.98，P=0.023）均为局部晚期ESCC患者pCR的独立影响因素；早期sPD-1下降≥30%（HR=0.44，95%CI为0.23~0.85，P=0.014）和基线sPD-1（HR=1.09，95%CI为1.02~1.18，P=0.021）均为局部晚期ESCC患者EFS的独立影响因素。不良事件总发生率为52.0%（65/125），以骨髓抑制和轻中度免疫相关反应为主，≥3级不良事件发生率为9.6%（12/125），未见治疗相关死亡。结论 新辅助卡瑞利珠单抗联合化疗过程中，sPD-1的基线水平及早期下降幅度与局部晚期ESCC患者的病理缓解及EFS显著相关。血清sPD-1作为一种简便、可动态监测的外周血标志物，有望成为新辅助免疫治疗疗效的预测工具。

关键词: 食道鳞癌, 新辅助化疗, 卡瑞利珠单抗, 程序性死亡受体1, 病理缓解

Abstract:

Objective To investigate the correlation between dynamic changes in serum soluble programmed death-1 （sPD-1） during neoadjuvant camrelizumab combined with chemotherapy and pathological response in patients with esophageal squamous cell carcinoma （ESCC）， and to evaluate the feasibility of sPD-1 as a predictive indicator of therapeutic efficacy. Methods A total of 125 patients with locally advanced ESCC who received neoadjuvant treatment with camrelizumab combined with albumin paclitaxel and cisplatin at Affiliated Huai′an No.1 People's Hospital of Nanjing Medical University from January 2019 to December 2021 were selected as the research subjects. Serum sPD-1 levels were measured at baseline， after the first cycle， after the second cycle， and before surgery. Patients were divided into the decreasing group （n=45） and non-decreasing group （n=80） based on early sPD-1 reduction （≥30% vs. <30%）. Correlations between sPD-1 dynamic changes and pathological complete response （pCR）， major pathological response （MPR）， and event-free survival （EFS） were analyzed using generalized estimating equation （GEE） models. Logistic regression model was used to identify the influencing factors of patients' pathological response； Kaplan-Meier curves were plotted to assess EFS in patients from the decreasing and non-decreasing groups， and the log-rank test was conducted； the Cox proportional hazards regression model was used to evaluate the influencing factors of patients' EFS. Results All 125 patients completed neoadjuvant therapy and surgery， with an R0 resection rate of 100% and no perioperative deaths. The baseline sPD-1 levels in the decreasing and non-decreasing groups were 5.9 （4.5， 7.3） and 5.7 （4.3， 7.6） ng/ml， respectively， with no statistically significant difference （Z=0.52， P=0.472）. Following the first treatment cycle， sPD-1 levels decreased to 3.1 （2.4， 4.0） ng/ml in the decreasing group and 4.8 （3.7， 6.5） ng/ml in the non-decreasing group， with a statistically significant difference （Z=19.26， P<0.001）. After the second treatment cycle， levels were 2.8 （2.2， 3.7） and 4.5 （3.4， 6.0） ng/ml， respectively， with a statistically significant difference （Z=22.13， P<0.001）. Before surgery， sPD-1 levels were 2.6 （2.0， 3.5） and 4.2 （3.3， 5.7） ng/ml，with a statistically significant difference （Z=21.84， P<0.001）. GEE analysis revealed that both the main effects of time （χ2=112.40， P<0.001） and group （χ2=7.63， P=0.006） were significant， and a significant interaction effect between time and group was observed （χ2=9.18， P=0.027）. After the first treatment cycle， the pCR rate for patients in decreasing group was 42.2% （19/45）， significantly higher than the 19.5% （16/80） in the non-decreasing group （χ2=7.59， P=0.006）. The MPR rate in the decreasing group was 68.9% （31/45）， significantly higher than that in the non-decreasing group， which was 48.1% （38/80） （χ2=5.35， P=0.021）. The survival analysis showed that the median EFS in the decreasing group was 34 months， longer than that of 28 months in the non-decreasing group （χ2=8.33， P=0.004）. Multivariate analysis indicated that an early reduction in sPD-1 of ≥30% （OR=2.34， 95%CI： 1.18-4.63， P=0.015） and baseline sPD-1 levels （OR=0.89， 95%CI： 0.80-0.98， P=0.023） were independent influencing factors of pCR in patients with locally advanced ESCC. Furthermore， early sPD-1 reduction ≥30% （HR=0.44， 95%CI： 0.23-0.85， P=0.014） and baseline sPD-1 （HR=1.09， 95%CI： 1.02-1.18， P=0.021） were identified as independent influencing factors for EFS in patients with locally advanced ESCC. The total incidence of adverse events was 52.0% （65/125）， mainly consisting of bone marrow suppression and mild to moderate immune-related reactions； the incidence of grade ≥3 adverse events was 9.6% （12/125）， with no treatment-related deaths. Conclusions Both baseline sPD-1 levels and early dynamic decline during neoadjuvant camrelizumab plus chemotherapy are significantly associated with pathological response and EFS in patients with locally advanced ESCC. Serum sPD-1， as a simple and dynamically monitorable peripheral blood marker， is expected to become a predictive tool for the efficacy of neoadjuvant immunotherapy.

Key words: Esophageal squamous cell carcinoma, Neoadjuvant chemotherapy, Camrelizumab, Programmed cell death-1, Pathological response