Introduction: Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. Methods: A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. Results: The median PFS was 2.7 (95% confidence interval [CI]: 1.4–4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0–18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86–2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. Conclusion: The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
Liver Cancer

中文翻译：

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Gd-EOB-DTPA 增强 MRI 肝胆期高增强肝内结节作为抗 PD-1/PD-L1 单药治疗不可切除肝细胞癌的不良反应标志物

简介：免疫检查点抑制剂（ICI）是治疗肝细胞癌（HCC）的有前途的药物。然而，建立可以预测对 ICI 反应的无创测量具有挑战性。本研究旨在使用钆-乙氧基苄基-二乙烯三胺 (Gd-EOB-DTPA) 的肝胆期增强磁共振成像 (MRI) 评估肿瘤对 ICI 的反应，该成像显示反映 Wnt/β-连环蛋白激活突变。方法：本研究共纳入 68 个肝内 HCC 结节，来自 18 名接受抗程序性细胞死亡 1 (PD-1)/程序性死亡配体 1 (PD-L1) 单药治疗的不可切除 HCC 和 Child-Pugh A 级肝功能患者学习。在治疗前 6 个月内，所有患者均存在可使用 Gd-EOB-DTPA 增强 MRI 的肝胆期评估的可行肝内病变。计算了相对增强率，并比较了高增强或低增强 HCC 结节之间的结节进展时间 (TTnP)，该时间定义为每个结节增加 20% 或更多。然后，根据实体瘤版本 1.1 (RECIST v1.1) 中的反应评估标准的无进展生存期 (PFS) 和客观反应率 (ORR)。结果：中位 PFS 为 2.7（95% 置信区间 [CI]：1.4-4.0）个月，增强较高的 HCC 结节（ n = 8）和低信号患者的 5.8（95% CI：0.0-18.9）个月HCC 结节 ( n = 10) ( p = 0.007)。增强程度较高的 HCC 结节 ( n = 23) 的中位 TTnP 为 1.97 (95% CI: 1.86-2.07) 个月，未达到低信号 HCC 结节 ( n = 45) 的中位 TTnP ( p = 0.003)。ORR 为 12.5% (1/8) 对 30.0% (3/10)；在有或没有高强化肝内 HCC 结节的患者中，疾病控制率分别为 37.5% (3/8) 和 70.0% (7/10)。结论：具有更高增强的 HCC 结节的 TTnP 和携带更高增强肝内 HCC 结节的患者的中位 PFS 显着短于抗 PD-1/PD-L1 单药治疗的低信号 HCC 结节。Gd-EOB-DTPA 增强 MRI 肝胆期结节的强度是预测 HCC 患者抗 PD-1/PD-L1 单药治疗不良反应的有前景的成像生物标志物。
肝癌