較高的基準嗜中性白血球與淋巴球的比率預測接受PD-1/PD-L1抑製劑的晚期肝細胞癌患者之惡化

A higher Baseline Neutrophil-to-lymphocyte Ratio Predicted the Progression of Disease in Patients with Advanced Hepatocellular Carcinoma Receiving PD-1/PD-L1 Inhibitors

針對肝細胞癌（HCC）之免疫檢查點抑製劑的主要挑戰之一是缺乏預測性生物標誌物。本研究目的在於探討接受細胞程序性死亡蛋白-1（PD-1）/細胞程式死亡配體-1（PD-L1）抑製劑治療的晚期HCC患者腫瘤反應的潛在預測因子。此回顧性與觀察性研究納入接受PD-1/PD-L1抑製劑治療的局部晚期或轉移性HCC患者。收集患者之基本資料、疾病特徵、檢驗數據、HCC分期、前期治療、腫瘤反應、不良事件（AE）和存活期。單變數和多變數存活率分析用於評估惡化（PD）的潛在預測因子。總共招募38名患者，其中完全反應為3例（7.9%）、部分反應10例（26.3%）、疾病穩定5例（13.2%）、PD 20例（52.6%）。客觀緩解率和疾病控制率分別為34.2%和47.4%。第3/4期和第5期之AE分別出現在10名（26.3%）和3名（7.9%）患者。多變數分析顯示，只有嗜中性白血球與淋巴球的比率（NLR）與PD有獨立相關（HR = 1.109, 95% CI = 1.004-1.225, P = 0.041）。此研究發現晚期HCC患者在接受PD-1/PD-L1抑製劑治療後，基準NLR > 2.5會增加10%的惡化風險。

The lack of predictive biomarkers is one of the major challenges in using immune checkpoint inhibitors for hepatocellular carcinoma (HCC). This study aimed to investigate potential predictors of tumor response in patients with advanced HCC treated with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors. This retrospective observational study included patients with locally advanced or metastatic HCC who received PD-1/PD-L1 inhibitors. This study collected demographics, disease characteristics, baseline laboratory data, HCC stage, previous therapies, tumor responses, adverse events (AEs), and survival. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the potential predictors of progressive disease (PD). Among 38 patients, three (7.9%) had complete responses, ten (26.3%) had partial responses, five (13.2%) had stable disease, and 20 (52.6%) had PD. The objective response rate and disease control rate were 34.2% and 47.4%, respectively. This study reported grade 3/4 and grade 5 AEs in ten (26.3%) and three (7.9%) patients, respectively. Multivariate analysis revealed that only neutrophil-to-lymphocyte ratio (NLR) was independently associated with PD (HR = 1.109, 95% CI = 1.004–1.225, P = 0.041). This study found that baseline NLR > 2.5 increased the risk of PD by10% after using PD-1/PD-L1 inhibitors in patients with advanced HCC.