AG或AG联合PD‑1抑制剂方案治疗可切除胰腺导管腺癌患者的预后及CCF风险评分的应用价值
Prognosis of patients with resectable pancreatic ductal adenocarcinoma treated by AG or AG combined with PD-1 inhibitor regimen and application value of CCF risk score
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摘要:目的 探讨吉西他滨联合白蛋白结合型紫杉醇(AG)或AG联合程序性死亡受体1(PD‑1)抑制剂方案治疗可切除胰腺导管腺癌(PDAC)患者的预后及克利夫兰医学中心(CCF)风险评分的应用价值。方法 采用回顾性队列研究方法。收集2013年1月至2024年3月浙江省肿瘤医院收治的151例行AG方案或AG联合PD‑1抑制剂方案治疗可切除PDAC患者的临床病理资料;男84例,女67例;年龄为(64±9)岁。观察指标:(1)不同CCF风险评分可切除PDAC患者的临床特征比较。(2)可切除PDAC患者总生存时间的影响因素分析。(3)可切除PDAC患者的生存情况。偏态分布的计量资料组间比较采用Mann‐Whitney U检验。计数资料组间比较采用χ²检验。等级资料组间比较采用秩和检验。单因素和多因素分析采用Cox回归模型。采用Kaplan‐Meier法计算生存率并绘制生存曲线,Log‑rank检验进行生存分析。结果 (1)不同CCF风险评分可切除PDAC患者的临床特征比较。根据CCF风险评分,151例患者中,102例为低风险,49例为中高风险,两者性别、年龄、吸烟、饮酒、高血压病、糖尿病比较,差异均有统计学意义(P<0.05)。(2)可切除PDAC患者总生存时间的影响因素分析。多因素分析结果显示:治疗方案是可切除PDAC患者总生存时间的独立影响因素(风险比=1.976,95%可信区间为1.065~3.666,P<0.05)。(3)可切除PDAC患者的生存情况。151例患者的随访时间为21.8(18.7,24.2)个月,中位总生存时间为23.3(19.0,32.4)个月。122例行AG方案治疗和29例行AG联合PD‑1抑制剂方案治疗患者的随访时间分别为22.1(18.9,30.7)个月和11.2(8.1,23.3)个月,中位总生存时间分别为24.4(17.2,31.7)个月和16.9(8.9,24.9)个月,1年总生存率分别为79.1%和60.0%,2年总生存率分别为53.4%和28.5%,两者总生存情况比较,差异有统计学意义(风险比=1.913,95%可信区间为1.041~3.516,P<0.05)。49例中高风险患者中,37例行AG方案治疗和12例行AG联合PD‑1抑制剂方案治疗患者的随访时间分别为18.5(8.8,28.1)个月和8.1(7.3,9.0)个月,中位总生存时间分别为32.4(15.7,49.0)个月和8.9(5.7,12.1)个月,1年总生存率分别为82.7%和31.3%,2年总生存率分别为66.5%和0,两者总生存情况比较,差异有统计学意义(风险比=5.402,95%可信区间为1.811~16.118,P<0.05)。结论 治疗方案是可切除PDAC患者总生存时间的独立影响因素。与AG联合PD‑1抑制剂方案比较,单纯AG方案治疗可切除PDAC的总生存情况较优。对于CCF风险评分中高风险患者,相较于AG联合PD‑1抑制剂方案,单纯AG方案治疗的总生存情况更优。Abstract:Objective To evaluate the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated by gemcitabine and nab-paclitaxel (AG) or AG combined with pro-grammed death-1 (PD-1) inhibitor regimen and application value of the Cleveland Clinic Foundation (CCF) risk score.Methods The retrospective cohort study was conducted. The clinicopathological data of 151 PDAC patients who were treated by AG regimen or AG combined with PD-1 inhibitor regimen in Zhejiang Cancer Hospital from January 2013 to March 2024 were collected. There were 84 males and 67 females, aged (64±9)years. Observation indicators: (1) comparison of clinical characteristics among resectable PDAC patients with different CCF risk score; (2) analysis of influencing factors for overall survival time of resectable PDAC patients; (3) survival of resectable PDAC patients. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis.Results (1) Comparison of clinical characteristics among resectable PDAC patients with different CCF risk score. Based on CCF risk score, 102 of 151 patients were classified as low risk and 49 cases were classified as intermediate-to-high risk. There were signi-ficant differences in sex, age, smoking status, alcohol consumption, hypertension, and diabetes between the two categories (P<0.05). (2) Analysis of influencing factors for overall survival time of resectable PDAC patients. Results of multivariate analysis showed that the treatment regimen was an indepen-dent influencing factor for overall survival time of resectable PDAC patients (hazard ratio=1.976, 95% confidence interval as 1.065‒3.666, P<0.05). (3) Survival of resectable PDAC patients. The follow-up time of 151 patients was 21.8(18.7,24.2)months, and the median overall survival time was 23.3(19.0,32.4)months. The follow-up time was 22.1(18.9,30.7)months of patients treated by AG regimen and 11.2(8.1,23.3)months of patients treated by AG combined with PD-1 inhibitor regimen, respectively. The median overall survival time of the two types of patients was 24.4(17.2,31.7)months and 16.9(8.9,24.9)months. The 1-year overall survival rates were 79.1% and 60.0%, and the 2-year overall survival rates were 53.4% and 28.5%, respectively. There was a significant difference in the overall survival between the two types of patients (hazard ratio=1.913, 95% confidence interval as 1.041‒3.516, P<0.05). Of the intermediate-to-high risk patients, the follow-up time was 18.5(8.8,28.1)months of 37 patients treated by AG regimen and 8.1(7.3,9.0)months of 12 patients treated by AG combined with PD-1 inhibitor regimen. The median overall survival time of the two types of patients was 32.4(15.7,49.0)months and 8.9(5.7,12.1)months, respectively. The 1-year overall survival rates were 82.7% and 31.3%, and the 2-year overall survival rates were 66.5% and 0, respectively. There was a significant difference in the overall survival between the two types of patients (hazard ratio=5.402, 95% confidence interval as 1.811‒16.118, P<0.05).Conclusions The treatment regimen is an independent influencing factor for overall survival in patients with resectable PDAC. Compared with the AG combined with PD-1 inhibitor regimen, AG regimen is associated with good survival of patients with resectable PDAC. For patients classified as intermediate-to-high risk based on the CCF risk score, AG regimen is assiociated with a better overall survival compared to AG combined with PD-1 inhibitor regimen.