Abstract：
Therapeutic options for large or locally advanced hepatocellular carcinoma (HCC) have limited efficacy. This study investigated the efficacy and safety of drug-eluting beads trans-arterial chemo-embolization (dTACE), portal vein embolization (PVE), tyrosine kinase inhibitor (TKI), and immune checkpoint inhibitors (ICI) compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for large or locally advanced HCC.Data regarding clinicopathological details, safety, and oncological outcomes were reviewed for the quadruple therapy (dTACE-PVE-TKI-ICI) and compared with ALPPS.From 2019 to 2020, 10 patients with large or locally advanced HCC underwent future remnant liver (FRL) modulation (dTACE-PVE-TKI-ICI: 5; ALPPS: 5). All five dTACE-PVE-TKI-ICI cases responded well, with patients #4 and #5 achieving complete tumor necrosis. The overall response rate (ORR) was 5/5. Patients #1-4 underwent hepatectomy, while #5 declined surgery due to complete tumor necrosis. Mean FRL volume increased by 75.3% (range 60.0%-89.4%) in 2-4 months, compared to 104.6% (range 51.3%-160.8%) in 21-37 days for ALPPS (P = 0.032). Major postoperative complications occurred in 1/5 ALPPS patients. Resection rates were 4/4 for quadruple therapy and 5/5 for ALPPS. 2-year progression free survival for dTACE-PVE-TKI-ICI and ALPPS were 5/5 and 3/5, respectively.Quadruple therapy is a feasible, effective strategy for enhancing resectability by downsizing tumors and inducing FRL hypertrophy, with manageable complications and improved long-term prognosis. In addition, it provokes the re-examination of the application of ALPPS in an era of molecular and immune treatments.
摘要：
大型或局部晚期肝细胞癌（HCC）的治疗选择疗效有限。这项研究调查了药物洗脱珠子经动脉化疗栓塞（dTACE）的疗效和安全性，门静脉栓塞术(PVE),酪氨酸激酶抑制剂（TKI），和免疫检查点抑制剂（ICI）相比，联合肝分区和门静脉结扎用于大型或局部晚期HCC的分期肝切除术（ALPPS）。有关临床病理细节的数据，安全,我们回顾了四联疗法(dTACE-PVE-TKI-ICI)的肿瘤结局,并与ALPPS进行了比较.从2019年到2020年，10例大型或局部晚期HCC患者接受了未来的残余肝脏（FRL）调制（dTACE-PVE-TKI-ICI：5;ALPPS：5）。所有五个dTACE-PVE-TKI-ICI案例反应良好，患者#4和#5实现完全肿瘤坏死。总响应率(ORR)为5/5。#1-4患者接受了肝切除术，而#5由于肿瘤完全坏死而拒绝手术。平均FRL体积在2-4个月内增加了75.3％（范围60.0％-89.4％），ALPPS在21-37天内为104.6%(范围51.3%-160.8%)(P=0.032)。1/5ALPPS患者发生主要术后并发症。四联疗法的切除率为4/4，ALPPS的切除率为5/5。dTACE-PVE-TKI-ICI和ALPPS的2年无进展生存期分别为5/5和3/5。四联疗法是可行的，通过缩小肿瘤和诱导FRL肥大来增强可切除性的有效策略，可控制的并发症和改善的长期预后。此外,它引发了对ALPPS在分子和免疫治疗时代的应用的重新审视。
