Katariya Nitin N, Lizaola-Mayo Blanca C, Chascsa David M, Giorgakis Emmanouil, Aqel Bashar A, Moss Adyr A, Uson Junior Pedro Luiz Serrano, Borad Mitesh J, Mathur Amit K
Department of Surgery, Division of Transplant and HPB Surgery, Mayo Clinic, Alix School of Medicine, Phoenix, AZ 85054, USA.
Department of Medicine, Division of Gastroenterology & Transplant Hepatology, Mayo Clinic, Alix School of Medicine, Phoenix, AZ 85054, USA.
Cancers (Basel). 2022 Apr 19;14(9):2056. doi: 10.3390/cancers14092056.
Hepatocellular Carcinoma (HCC) is the most common liver malignancy and third leading cause of cancer death worldwide. For early- and intermediate-stage disease, liver-directed therapies for locoregional control, or down-staging prior to definitive surgical therapy with hepatic resection or liver transplantation, have been studied broadly, and are the mainstays of current treatment guidelines. As HCC incidence has continued to grow, and with more patients presenting with advanced disease, our current treatment modalities do not suffice, and better therapies are needed to improve disease-specific and overall survival. Until recently, sorafenib was the only systemic therapy utilized, and was associated with dismal results. The advent of immuno-oncology has been of significant interest, and has changed the paradigm of therapy for HCC. Lately, combination regimens including atezolizumab plus bevacizumab; durvalumab plus tremelimumab; and pembrolizumab plus Lenvatinib have shown impressive responses of between 25-35%; this is much higher than responses observed with single agents. Complete responses with checkpoint inhibitor therapy have been observed in advanced-stage HCC patients. These dramatic results have naturally led to several questions. Can or should checkpoint inhibitors, or other immunotherapy combinations, be used routinely before resection or transplant? Is there a synergistic effect of immunotherapy with locoregional therapy, and will pre-treatment increase disease-free survival after surgical intervention? Is it immunologically safe to use these therapies prior to transplantation? Much is still to be learned in terms of the dosing, timing, and overall utility of the use of immune checkpoint inhibitors for pre-transplant care and down-staging. More studies will be needed to understand the management of adverse events while maximizing the therapeutic window of these agents. In this review, we look at the current data on therapy with immune checkpoint inhibitors in advanced HCC, with a focus on pre-transplant treatment prior to liver transplant.
肝细胞癌（HCC）是最常见的肝脏恶性肿瘤，也是全球癌症死亡的第三大主要原因。对于早期和中期疾病，针对局部区域控制的肝脏定向治疗，或在进行肝切除或肝移植等确定性手术治疗之前进行降期治疗，已得到广泛研究，并且是当前治疗指南的主要内容。随着HCC发病率持续上升，以及越来越多的患者出现晚期疾病，我们目前的治疗方式已不足以应对，因此需要更好的治疗方法来提高疾病特异性生存率和总生存率。直到最近，索拉非尼是唯一使用的全身治疗药物，但其效果不佳。免疫肿瘤学的出现引起了极大关注，并改变了HCC的治疗模式。最近，包括阿替利珠单抗联合贝伐单抗、度伐利尤单抗联合曲美木单抗以及帕博利珠单抗联合乐伐替尼在内的联合方案已显示出令人印象深刻的25%-35%的缓解率；这远高于单药治疗的缓解率。在晚期HCC患者中已观察到检查点抑制剂治疗的完全缓解。这些显著的结果自然引发了几个问题。检查点抑制剂或其他免疫治疗组合能否或是否应该在切除或移植前常规使用？免疫治疗与局部区域治疗是否存在协同作用，术前治疗是否会提高手术干预后的无病生存率？移植前使用这些疗法在免疫方面是否安全？在免疫检查点抑制剂用于移植前护理和降期治疗的剂量、时机和总体效用方面，仍有许多需要了解的地方。需要更多研究来了解在最大化这些药物治疗窗口的同时对不良事件的管理。在这篇综述中，我们着眼于晚期HCC免疫检查点抑制剂治疗的当前数据，重点关注肝移植前的移植前治疗。
