Chen Shiyun, Guo Shiyuan, Gou Miaomiao, Pan Yuting, Fan Mengjiao, Zhang Nan, Tan Zhaoli, Dai Guanghai
Medical School of Chinese People's Liberation Army, Beijing, China.
Department of Oncology, The First Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China.
Front Oncol. 2022 Oct 25;12:951985. doi: 10.3389/fonc.2022.951985. eCollection 2022.
There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy.
Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit.
There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis.
The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.
目前尚无已确立的生物标志物能够预测晚期胰腺癌（PC）患者是否会从免疫检查点抑制剂（ICI）中获益。我们的研究调查了预处理时的复合生物标志物——衍生中性粒细胞与淋巴细胞比值（dNLR）和乳酸脱氢酶（LDH）是否可作为接受PD-1抑制剂治疗的PC患者生存的可靠预后因素。
纳入2015年9月至2020年9月在单中心接受PD-1抑制剂治疗的晚期PC患者。dNLR水平高（≥3）和LDH水平高（≥250 U/L）被视为危险因素。基于这两个危险因素，本研究中的患者被分为两个风险组：无危险因素的良好dNLR-LDH组和有一至两个危险因素的中/差dNLR-LDH组。总生存期（OS）和无进展生存期（PFS）作为本研究的主要和次要终点。采用Cox回归模型确定生存获益的独立预后因素。
本研究中有98例患者。良好组包括61例（62.2%）患者，中/差组包括37例（37.8%）患者。接受免疫治疗的总体PC患者的中位OS为12.1个月，良好dNLR-LDH组的OS明显长于中/差dNLR-LDH组（44.2个月对6.4个月；p<0.0***）；中位PFS分别为3.7个月和2.5个月（p = 0.010）。多因素分析显示，转移部位数>2以及免疫治疗为三线或更晚与更差的PFS相关，免疫治疗线数和dNLR-LDH指标是OS的独立预后因素。
dNLR和LDH的预处理复合生物标志物可作为接受PD-1抑制剂治疗的晚期PC患者的预后生物标志物。
