Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA.
Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY.
Hepatology. 2020 Dec;72(6):2014-2028. doi: 10.1002/hep.31210.
The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).
Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001).
In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
器官获取与移植网络最近批准对米兰标准（MC）以外的肝细胞癌（HCC）患者进行肝移植（LT）优先排序，这些患者通过局部区域治疗（LRT）降期。我们评估了来自美国多中心 HCC 移植联盟（20 个中心，2002-2013 年）中 MC 内（n=3570）和 MC 以外（n=789）的降期（n=465）、接受 LRT 治疗且未降期（LRT-NoDS，n=242）或未接受治疗（NoLRT-NoDS，n=82）患者的 LT 后结局、降期预测因素以及 LRT 的影响。
比较了 MC 内（n=3570）和 MC 以外（n=789）降期（n=465）、接受 LRT 治疗且未降期（LRT-NoDS，n=242）或未接受治疗（NoLRT-NoDS，n=82）患者的临床病理特征、总生存期（OS）、无复发生存期（RFS）和 HCC 复发（HCC-R）。与 MC 内患者相比，LT 后 5 年 OS（64.3% vs. 71.3%）和 RFS（59.5% vs. 68.2%）在 DS 患者中较低，在 NoDS 患者中最低（n=324；60.2%和 53.8%；总体 P<0.001）。DS 患者的 RFS（60% vs. 54%，P=0.043）和 5 年 HCC-R（18% vs. 32%，P<0.001）优于 NoDS，进一步分层分析最大影像学肿瘤直径（DS/<5 cm 患者的 5 年 HCC-R 为 15.5%，NoDS/>5 cm 患者的 HCC-R 为 39.1%，P<0.001）。降期的多变量预测因素包括 LRT 治疗的 AFP 反应、肿瘤数量和大小以及等待时间>12 个月。与 NoLRT-NoDS 相比，LRT-NoDS 患者的 HCC-R 更高（34.1% vs. 26.1%，P<0.001），即使在控制了临床病理变量后（风险比[HR]为 2.33，P<0.001）和逆概率治疗加权倾向匹配（HR 为 1.82，P<0.001）。
在 MC 以外接受 HCC 治疗的 LT 受者中，等待时间、LRT 治疗后的 AFP 反应和肿瘤负担可预测降期，且 LT 后结局优异，这证明 LT 标准的扩展是合理的。在 LRT-NoDS 患者中，与 NoLRT-NoDS 相比，更高的 HCC-R 不能用临床病理差异来解释，这表明 LRT 在肿瘤生物学较差的患者中可能具有潜在的恶化作用，这需要进一步研究。
