免疫疗法期间明显加速肿瘤生长被视为一种新的进展模式，被称为高速进展性疾病（hyperprogressive disease, HPD），但其对接受免疫疗法的胰腺癌（pancreatic cancer, PC）患者的影响尚不清楚。本研究描述和研究了接受程序性细胞死亡配体-1（programmed cell death-1, PD-1）抑制剂治疗的晚期PC患者中HPD的发生率、预后和预测因素。我们对2015-2020年在我们机构接受PD-1抑制剂治疗的104名晚期胰腺癌患者的临床病理数据进行了回顾性分析，并确认了10例（9.6%）HPD患者。与进展性疾病（progressive disease, PD）患者相比，HPD患者的总生存期（overall survival, OS）显著较差（中位OS：5.6 vs. 3.6个月，p < .01）。与HPD发生相关的临床病理因素包括吸烟、转移灶数量>2、肝转移、免疫疗法前21天内接受抗生素治疗（Abx B21）、血红蛋白水平<110 g/L和PD-1抑制剂治疗线>2。亚组分析显示，基线时高水平的CA19-9与后续HPD的发展（p = .024）及较差预后（中位OS：16.2个月 vs. 6.1个月，p < .01）相关。我们的研究表明，在接受PD-1抑制剂治疗的PC患者中可能出现HPD，并与一些临床病理特征和差预后相关。基线肿瘤标志物CA19-9可能是PC患者接受免疫疗法后发生HPD的早期预测因子之一。

The occurrence of markedly accelerated tumor growth during immunotherapy is considered a new mode of progression called hyperprogressive disease (HPD) and its impact on pancreatic cancer (PC) patients receiving immunotherapy is unknown. In this study, we described and explored the incidence, prognosis and predictors of HPD in patients with advanced PC treated with programmed cell death-1 (PD-1) inhibitors. We retrospectively analyzed clinicopathological data from 104 patients with advanced pancreatic cancer who were treated with PD-1 inhibitors at our institution during 2015-2020 and identified 10 (9.6%) patients with HPD. Overall survival (OS) was significantly poorer in patients with HPD compared to patients with progressive disease (PD) (median OS: 5.6 vs. 3.6 months, p < .01). Clinicopathological factors associated with the occurrence of HPD included smoking, metastatic sites >2, liver metastasis, antibiotic therapy within 21 days before immunotherapy (Abx B21), hemoglobin (Hb) level <110 g/L, and PD-1 inhibitor treatment line >2. Subgroup analysis showed that high levels of CA19-9 at baseline were associated with the development of subsequent HPD (p = .024) and a worse prognosis (mOS:16.2 months vs. 6.1 months, p < .01). Our study demonstrated that HPD may occur in PC patients treated with PD-1 inhibitors and is associated with several clinicopathological characteristics and poor prognosis. The baseline tumor marker CA19-9 may be one of the early predictors of HPD development in PC patients receiving immunotherapy.