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抗程序性死亡蛋白1(PD1)免疫疗法和循环肿瘤细胞对手术切除的胰腺腺癌无进展生存期的影响:一项回顾性队列研究

Impact of anti-PD1 immunotherapy and circulating tumor cells on progression-free survival in surgical pancreatic adenocarcinoma: a retrospective cohort study.

作者信息

He Yong-Gang, Zhu Yi-Nan, Xiao Zhou-You, Wang Zheng, Wang Chao-Qun, Huang Xiao-Bing, Zheng Lu

机构信息

Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing, China.

出版信息

Expert Rev Clin Immunol. 2025 Mar;21(3):359-368. doi: 10.1080/1744666X.2024.2448989. Epub 2025 Jan 5.

Abstract

INTRODUCTION

The clinical benefits of combining immunotherapy with chemotherapy and surgical resection in pancreatic adenocarcinoma remain unclear. The expression and clinical significance of HIF1A in circulating tumor cells (CTCs) in pancreatic adenocarcinoma remains limited.

METHODS

This retrospective cohort study compared survival outcomes in pancreatic adenocarcinoma patients treated with two regimens: surgery+chemotherapy (nab-paclitaxel plus gemcitabine)+anti-PD1 (Tislelizumab) (S+AG+anti-PD1) ( = 37), and surgery+chemotherapy (S+AG) ( = 5). The study also evaluated CTCs and HIF1A-positive CTCs as potential prognostic biomarkers.

RESULTS

The S+AG+anti-PD1 group ( = 37) showed significantly better progression-free survival (PFS) compared to S+AG ( = 15) in multivariate analysis (HR: 0.426, 95% CI: 0.185-0.983,  = 0.045). Overall survival (OS) differences were not statistically significant between groups. Lower CTC counts (≤1) were associated with longer PFS in surgical patients. This association was confirmed in multivariate analysis, after adjustment for AJCC stages (HR: 0.318, 95% CI: 0.104-0.974,  = 0.045). HIF1A-positive CTCs showed similar trends and prognostic significance to total CTC counts. Advanced AJCC stages remained the strongest independent predictor of worse PFS and OS.

CONCLUSION

Combining surgery, chemotherapy, and immunotherapy may improve PFS in resectable pancreatic adenocarcinoma. While CTCs and HIF1A-positive CTCs may have prognostic value, AJCC staging remains the most reliable indicator.

摘要

引言

免疫疗法与化疗及手术切除联合用于胰腺腺癌的临床益处仍不明确。缺氧诱导因子1α(HIF1A)在胰腺腺癌循环肿瘤细胞(CTC)中的表达及临床意义仍有限。

方法

这项回顾性队列研究比较了接受两种治疗方案的胰腺腺癌患者的生存结局:手术+化疗(白蛋白结合型紫杉醇加吉西他滨)+抗程序性死亡蛋白1(PD1)(替雷利珠单抗)(S+AG+抗PD1)(n = 37),以及手术+化疗(S+AG)(n = 15)。该研究还评估了CTC及HIF1A阳性CTC作为潜在预后生物标志物的情况。

结果

在多因素分析中,S+AG+抗PD1组(n = 37)与S+AG组(n = 15)相比,无进展生存期(PFS)显著更好(风险比:0.426,95%置信区间:0.185 - 0.983,P = 0.045)。两组间总生存期(OS)差异无统计学意义。手术患者中较低的CTC计数(≤1)与更长的PFS相关。在对美国癌症联合委员会(AJCC)分期进行校正后的多因素分析中证实了这种关联(风险比:0.318,95%置信区间:0.104 - 0.974,P = 0.045)。HIF1A阳性CTC显示出与总CTC计数相似的趋势和预后意义。AJCC晚期仍然是PFS和OS较差的最强独立预测因素。

结论

手术、化疗和免疫疗法联合应用可能改善可切除胰腺腺癌的PFS。虽然CTC和HIF1A阳性CTC可能具有预后价值,但AJCC分期仍然是最可靠的指标。

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