Abstract: Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, systemic therapy, transarterial chemoembolization, hepatic artery infusion chemotherapy, radiotherapy, multimodality treatment, liver resection, liver transplantation


中文翻译：

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门静脉肿瘤血栓形成和肝细胞癌——不断变化的潮流

摘要：门静脉受累被认为是肝细胞癌 (HCC) 最可怕的并发症之一。门静脉肿瘤血栓形成 (PVTT) 与侵袭性肿瘤生物学（高级别）、高肿瘤负荷（病变的数量和大小）、高水平的血清标志物 (AFP)、肝功能差（LFT 紊乱）和较差的体能状态相关的患者。巴塞罗那诊所肝癌分期系统将具有 PVTT 的 HCC 患者置于晚期（BCLC 阶段-C）。该组包含相当异质的患者群体，以前被认为是索拉非尼姑息性全身治疗的候选者。然而，这提供了适度的总生存期 (OS) 益处。最近的 III 期 (IMbrave150) 试验的结果支持将 atezolizumab 和贝伐珠单抗的组合优于索拉非尼作为晚期不可切除 HCC 的护理标准。虽然只有乐伐替尼在 III 期（REFLECT 试验）中被证明不劣于索拉非尼，但瑞戈非尼（RESORCE 试验）、雷莫芦单抗（REACH-2）和卡博替尼（CELESTIAL）已在 III 期临床试验中被批准作为二线治疗. 最近，关于使用 PVTT 管理 HCC 的其他方式前景的数据正在增加，并取得了良好的结果。使用药物和其他方式（如 RT、TACE、TARE 和 HAIC）的组合靶向 HCC 级联中的多个途径，似乎对全身和局部区域控制有效。对理想的联合治疗和序列集的探索仍然广泛没有答案，也缺乏前瞻性试验。随着可用治疗选择的武装以及输送系统的进步和改进，已报道将患者降期以使他们有资格进行根治性切除术。在快速发展的治疗环境中，在适当的时候以 LR 甚至 LT 的形式进行手术以实现治愈似乎并不牵强。同样，辅助治疗和及时管理复发是延长 OS 和 DFS 的关键。本综述讨论了具有 PVTT 的 HCC 患者的管理选择。

关键词：肝细胞癌，门静脉肿瘤血栓形成，全身治疗，经动脉化疗栓塞，肝动脉灌注化疗，放疗，多模式治疗，肝切除术，肝移植