国际肿瘤学杂志 ›› 2024, Vol. 51 ›› Issue (3): 157-165.doi: 10.3760/cma.j.cn371439-20231016-00025

• 论著 • 上一篇    下一篇

早期肿瘤标志物联合NLR、PLR预测胃癌免疫治疗疗效

解淑萍1,2, 孙亚红3(), 汪超4()   

  1. 1山东第一医科大学(山东省医学科学院)研究生院,济南 250117
    2山东第一医科大学第三附属医院肿瘤内科,济南 250031
    3山东省立第三医院肿瘤中心,济南 250031
    4山东第一医科大学第二附属医院肿瘤微创病区,泰安 271099
  • 收稿日期:2023-10-16 修回日期:2023-12-19 出版日期:2024-03-08 发布日期:2024-04-10
  • 通讯作者: 孙亚红,Email: sunyahong@sdfmu.edu.cn;汪超,Email: wangchaogongzuo@126.com

Prediction of efficacy of early-stage tumor markers combined with NLR and PLR for immunotherapy in gastric cancer

Xie Shuping1,2, Sun Yahong3(), Wang Chao4()   

  1. 1Department of Graduate School, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China
    2Department of Medical Oncology, Third Affiliated Hospital of Shandong First Medical University, Jinan 250031, China
    3Department of Cancer Center, Shandong Provincial Third Hospital, Jinan 250031, China
    4Department of Minimally Invasive Tumor Ward, Second Affiliated Hospital of Shandong First Medical University, Tai'an 271099, China
  • Received:2023-10-16 Revised:2023-12-19 Online:2024-03-08 Published:2024-04-10
  • Contact: Sun Yahong, Email: sunyahong@sdfmu.edu.cn; Wang Chao, Email: wangchaogongzuo@126.com

摘要:

目的 探讨早期血清肿瘤标志物(STM)、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)联合评分对胃癌免疫治疗疗效的预测价值。方法 选取2020年1月1日至2022年6月30日于山东第一医科大学第二附属医院接受免疫治疗的76例胃癌患者,收集患者前导的STM、NLR、PLR,通过受试者操作特征(ROC)曲线确定NLR、PLR最佳截断值。分析不同前导的STM、NLR、PLR及联合评分接受免疫治疗胃癌患者的临床疗效及预后。采用ROC曲线评估各指标及联合评分的预测效能。采用Cox回归模型对患者生存期的影响因素进行分析。结果 NLR最佳截断值为2.75,PLR最佳截断值为175.9。所有患者均至少完成了2个周期的免疫治疗,客观缓解率(ORR)为23.7%(18/76),疾病控制率(DCR)为88.2%(67/76)。高NLR组(n=43)和低NLR组(n=33)ORR[20.9%(9/43)比27.3%(9/33)]、DCR[83.7%(36/43)比93.9%(31/33)]差异均无统计学意义(χ2=0.42,P=0.519;χ2=1.02,P=0.313);高PLR组(n=44)和低PLR组(n=32)ORR[27.3%(12/44)比18.8%(6/32)]、DCR[81.8%(36/44)比96.9%(31/32)]差异均无统计学意义(χ2=0.75,P=0.388;χ2=2.71,P=0.555);高联合评分组(n=39)和低联合评分组(n=37)ORR分别为17.9%(7/39)、29.7%(11/37),差异无统计学意义(χ2=1.46,P=0.230);DCR分别为79.5%(31/39)、97.3%(36/37),差异有统计学意义(χ2=4.19,P=0.041)。76例患者中位无进展生存期(PFS)和总生存期(OS)分别为8.0、12.0个月。高NLR组和低NLR组患者中位PFS分别为7.0、10.0个月,差异有统计学意义(χ2=7.95,P=0.005);中位OS分别为12.0、14.0个月,差异无统计学意义(χ2=1.04,P=0.307)。高PLR组和低PLR组患者中位PFS分别为8.0、10.0个月,差异有统计学意义(χ2=3.90,P=0.048);中位OS分别为13.0、13.0个月,差异无统计学意义(χ2=0.02,P=0.896)。高联合评分组和低联合评分组患者中位PFS分别为7.0、10.0个月,差异有统计学意义(χ2=13.52,P<0.001);中位OS分别为12.0、14.0个月,差异有统计学意义(χ2=5.02,P=0.025)。ROC曲线分析显示,前导的STM、NLR、PLR和联合评分预测胃癌免疫治疗疗效的曲线下面积(AUC)分别为0.662、0.697、0.601、0.773。单因素分析显示,手术(HR=0.59,95%CI为0.36~0.95,P=0.031)、前导的STM(HR=0.57,95%CI为0.34~0.93,P=0.026)、NLR(HR=0.54,95%CI为0.34~0.87,P=0.011)、联合评分(HR=0.42,95%CI为0.26~0.68,P<0.001)均是接受免疫治疗胃癌患者PFS的影响因素;肿瘤分期(HR=0.30,95%CI为0.12~0.75,P=0.011)、前导的STM(HR=0.28,95%CI为0.15~0.50,P<0.001)、联合评分(HR=0.55,95%CI为0.31~0.96,P=0.036)均是接受免疫治疗胃癌患者OS的影响因素。多因素分析显示,前导的STM(HR=0.56,95%CI为0.33~0.98,P=0.041)是接受免疫治疗胃癌患者PFS的独立影响因素;肿瘤分期(HR=0.29,95%CI为0.11~0.76,P=0.012)、前导的STM(HR=0.32,95%CI为0.17~0.58,P<0.001)、联合评分(HR=0.46,95%CI为0.25~0.82,P=0.009)均是接受免疫治疗胃癌患者OS的独立影响因素。结论 前导的STM、NLR、PLR的联合评分是接受免疫治疗胃癌患者OS的独立影响因素,可预测胃癌免疫治疗疗效。

关键词: 胃肿瘤, 生物标记, 肿瘤, 免疫检查点抑制剂, 中性粒细胞与淋巴细胞比值, 血小板与淋巴细胞比值

Abstract:

Objective To explore the predictive value of early serum tumor markers (STM), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) combination score on the efficacy of gastric cancer immunotherapy. Methods A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1, 2020 to June 30, 2022 were selected. Patients' leading STM, NLR, PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic (ROC) curve. The clinical efficacy and prognosis of different leading STM, NLR, PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival. Results The best truncation value for NLR was 2.75, and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy, the objective response rate (ORR) was 23.7% (18/76), and the disease control rate (DCR) was 88.2% (67/76). There were no significant differences in ORR [(20.9% (9/43) vs. 27.3% (9/33)], DCR [83.7% (36/43) vs. 93.9% (31/33)] between the high NLR group (n=43) and low NLR group (n=33) (χ2=0.42, P=0.519; χ2=1.02, P=0.313). There were no significant differences in ORR [27.3% (12/44) vs. 18.8% (6/32)], DCR [81.8% (36/44) vs. 96.9% (31/32)] between the high PLR group (n=44) and low PLR group (n=32) (χ2=0.75, P=0.388; χ2=2.71, P=0.555). The ORR for the high combined score group (n=39) and low combined score group (n=37) was 17.9% (7/39) and 29.7% (11/37), respectively, with no statistically significant difference (χ2=1.46, P=0.230); the DCR was 79.5% (31/39) and 97.3% (36/37), respectively, with a statistically significant difference (χ2=4.19, P=0.041). The median progression free survival (PFS) and overall survival (OS) of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months, respectively, with a statistically significant difference (χ2=7.95, P=0.005); the median OS was 12.0 and 14.0 months, respectively, with no statistically significant difference (χ2=1.04, P=0.307). The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months, respectively, with a statistically significant difference (χ2=3.90, P=0.048); the median OS was 13.0 and 13.0 months, respectively, with no significant difference (χ2=0.02, P=0.896). The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months, respectively, with a statistically significant difference (χ2=13.52, P<0.001); the median OS was 12.0 and 14.0 months, respectively, with a statistically significant difference (χ2=5.02, P=0.025). ROC curve analysis showed that the area under curve (AUC) of leading STM, NLR, PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662, 0.697, 0.601 and 0.773. Univariate analysis showed that, surgery (HR=0.59, 95%CI: 0.36-0.95, P=0.031), leading STM (HR=0.57, 95%CI: 0.34-0.93, P=0.026), NLR (HR=0.54, 95%CI: 0.34-0.87, P=0.011), combined score (HR=0.42, 95%CI: 0.26-0.68, P<0.001) were all influencing factors for PFS in gastric cancer patients received immunotherapy; tumor stage (HR=0.30, 95%CI: 0.12-0.75, P=0.011), leading STM (HR=0.28, 95%CI: 0.15-0.50, P<0.001), combined score (HR=0.55, 95%CI: 0.31-0.96, P=0.036) were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that, leading STM (HR=0.56, 95%CI: 0.33-0.98, P=0.041) was an independent influencing factor for PFS in gastric cancer patients received immunotherapy; tumor stage (HR=0.29, 95%CI: 0.11-0.76, P=0.012), leading STM (HR=0.32, 95%CI: 0.17-0.58, P<0.001), combined score (HR=0.46, 95%CI: 0.25-0.82, P=0.009) were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion The combined score of leading STM, NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer, and can predict the efficacy of immunotherapy for gastric cancer.

Key words: Stomach neoplasms, Biomarkers, tumor, Immune checkpoint inhibitors, Neutrophil to lymphocyte ratio, Platelet to lymphocyte ratio