PPI对PD-1抑制剂治疗肝细胞癌效果的影响--PSM分析联合Nomogram预后预测分析

The effect of PPI on the treatment of hepatocellular carcinoma with PD-1 inhibitors:PSM analysis combined with Nomogram prediction of the prognosis

目的探讨质子泵抑制剂(PPI)对肝细胞癌(HCC)患者使用程序性细胞死亡蛋白-1(PD-1)抑制剂治疗的预后影响。方法回顾性分析接受PD-1抑制剂治疗的148例HCC患者的临床资料,根据HCC患者PPI药物使用强度(PUD)的中位数将患者分为PPI高剂量组和低剂量组,研究PPI的使用对HCC患者总生存期(OS)的影响并分析其他可能影响生存和预后的独立危险因素,构建列线图(Nomogram)预测模型。结果基线资料倾向性评分匹配(PSM)前,使用高剂量PPI(HR 2.32,95%CI 1.41~3.80,P=0.001)是影响接受PD-1抑制剂治疗的HCC患者OS的独立危险因素,生存曲线分析提示PPI高剂量组的HCC患者其生存时间较低剂量组短。PSM后,使用高剂量PPI(HR 2.57,95%CI 1.32~4.98,P=0.005)仍然是影响接受PD-1抑制剂治疗的HCC患者OS的独立危险因素。构建Nomogram模型预测HCC患者OS,其6、12和18个月的ROC曲线下面积(AUC)分别为0.781、0.761和0.791。在预后预测方面,Nomogram预测模型与传统肿瘤分期系统相比表现出非劣势性。结论接受PD-1抑制剂治疗的HCC患者使用高剂量PPI提示预后更差,结合包括PPI使用情况和临床特征建立的Nomogram模型对OS具有一定预测能力。

Objective To investigate the effect of proton pump inhibitors(PPI)on of the prognosis of hepatocellular carcinoma(HCC)patients treated with programmed cell death-1(PD-1)inhibitor.Methods The clinical data of 148 HCC patients who treated with PD-1 inhibitor were retrospectively analyzed.The effect of PPI on overall survival(OS)of HCC patients,and other independent risk factors that may affect survival and prognosis were analyzed to construct a Nomogram model.HCC patients were divided into high-dose PPI group and low-dose PPI group according to the median PPI use density(PUD).Results Before propensity score matching(PSM),high dose of PPI was an independent risk factor affecting OS of HCC patients with PD-1 inhibitor(HR 2.32,95%CI 1.41-3.80,P=0.001).According to survival curve analysis,compared with the lowdose group,HCC patients in high-dose group were associated with worse outcome.After PSM,high dose of PPI was also an independent risk factor affecting OS of HCC patients with PD-1 inhibitor(HR 2.57,95%CI 1.32-4.98,P=0.005).A Nomogram model for prediction OS was developed,the areas under the ROC(AUC)at 6,12 and 18 months were 0.781,0.761 and 0.791,respectively.Compared with traditional tumor stage,the Nomogram showed non-inferiority in prediction of HCC prognosis.Conclusion For HCC patients treated with PD-1 inhibitors,the high-dose PPI suggests a worse prognosis.The clinical prediction model develeped with PPI and Nomogram model shows certain predictive ability for OS.