Supplementary Material for: Predictive Value of the Hepatic Immune Predictive Index for Patients with Primary Liver Cancer Treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. However, its efficacy is limited by the risk of tumor recurrence, resulting in rapid death and graft loss if patients are not selected appropriately. Therefore, it is necessary to identify patients suitable for such therapy. Methods: 215 patients with primary liver cancer with immunotherapy were screened between August 2018 and October 2020 as a training set and our validation set were included 71 patients of hepatocellular carcinoma from Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College from May 2019 to July 2021. The primary endpoint was the disease control rate (DCR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: In the traing set, Neutrophil-leukocyte ratio (NLR) >3, Alpha-fetoprotein (AFP) level >20 ng/ml, distant metastasis at baseline, and absence of combination with targeted therapy were associated with non-DCR in the training set. Moreover, NLR >3 and AFP level >20 ng/ml were also independently associated with OS. Furthermore, a hepatic immune predictive index (HIPI) based on NLR >3 and AFP level >20 ng/mL was developed and associated with worse clinical outcomes. In validation set, HIPI was associated with overall survival. Conclusion: Baseline hepatic immune predictive index based on NLR and AFP level is an effective indicator in ICI-treated patients with primary liver cancer. Our findings may help guide the selection and on-treatment strategies for immunotherapies for primary liver cancer patients.

背景：免疫检查点抑制剂（Immune Checkpoint Inhibitors, ICIs）已使部分原发性肝癌患者获得生存改善，并实现长期临床应答。然而其疗效受肿瘤复发风险制约，若未对患者进行合理筛选，可导致患者快速死亡及移植物丢失。因此，亟需筛选出适合接受该类治疗的患者群体。
方法：2018年8月至2020年10月期间，共筛选215例接受免疫治疗的原发性肝癌患者作为训练集；本研究的验证集纳入2019年5月至2021年7月期间，来自江西省肿瘤医院、南昌医学院第二附属医院的71例肝细胞癌患者。本研究的主要终点为疾病控制率（Disease Control Rate, DCR），次要终点为总生存期（Overall Survival, OS）与无进展生存期（Progression-Free Survival, PFS）。
结果：在训练集中，中性粒细胞-白细胞比值（Neutrophil-leukocyte Ratio, NLR）＞3、甲胎蛋白（Alpha-Fetoprotein, AFP）水平＞20 ng/ml、基线存在远处转移、未联合靶向治疗，均与患者未达到疾病控制率显著相关。此外，NLR＞3及AFP水平＞20 ng/ml也与总生存期独立相关。本研究进一步基于NLR＞3与AFP水平＞20 ng/mL构建了肝脏免疫预测指数（Hepatic Immune Predictive Index, HIPI），该指数与更差的临床结局显著相关。在验证集中，HIPI与患者总生存期显著相关。
结论：基于中性粒细胞-白细胞比值与甲胎蛋白水平构建的基线肝脏免疫预测指数，可作为接受免疫检查点抑制剂治疗的原发性肝癌患者的有效预后指标。本研究结果可为原发性肝癌患者免疫治疗的患者筛选及治疗期间策略制定提供临床指导依据。