Khan Abdul Rehman, Wei Xuyong, Xu Xiao
Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.
J Hepatocell Carcinoma. 2021 Sep 7;8:1089-1115. doi: 10.2147/JHC.S318070. eCollection 2021.
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.
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行为（高分级）、高肿瘤负荷（病灶数量和大小）、高血清标志物水平（甲胎蛋白）、肝功能差（肝功能检查紊乱）以及患者的低体能状态相关。巴塞罗那临床肝癌分期系统将伴有PVTT的HCC患者归为晚期（BCLC C期）。这组患者群体相当异质，以前被认为是索拉非尼姑息性全身治疗的候选者。然而，这仅带来适度的总生存期（OS）获益。最近一项III期（IMbrave150）试验结果表明，在晚期不可切除HCC中，阿替利珠单抗和贝伐单抗联合用药优于索拉非尼，可作为标准治疗方案。虽然在一项III期（REFLECT试验）中只有乐伐替尼被证明与索拉非尼疗效相当，但瑞戈非尼（RESORCE试验）、雷莫西尤单抗（REACH-2）和卡博替尼（CELESTIAL）已在III期临床试验中被批准用于二线治疗。最近，关于其他治疗方式在伴有PVTT的HCC治疗中的前景的数据不断增加，且结果良好。联合使用药物以及放疗、经动脉化疗栓塞（TACE）、钇90微球肝动脉内放射栓塞（TARE）和肝动脉灌注化疗（HAIC）等其他方式，针对HCC级联反应中的多个途径进行靶向治疗，似乎对全身和局部区域控制有效。对于理想的联合治疗方案及其顺序设定的探索仍未得到广泛解答，且缺乏前瞻性试验。随着现有治疗选择的增加以及给药系统的进步和改进，已有报道称可使患者降期，使其有资格接受根治性切除。在快速发展的治疗格局中，在适当的时候以肝切除（LR）甚至肝移植（LT）的形式进行手术以实现治愈似乎并非遥不可及。同样，辅助治疗以及对复发的及时处理是延长OS和无病生存期（DFS）的关键。本综述讨论了伴有PVTT的HCC患者的治疗选择。
