Liver Transplantation Outcomes in a US Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria
Liver Transplantation Outcomes in a US Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria
复制标题
DOI：
10.1002/hep.31210
复制
发表时间：
2020-12-01
期刊：
影响因子：
13.5
通讯作者：
Agopian, Vatche G.
中科院分区：
文献类型：
--
作者：
Kardashian, Ani;Florman, Sander S.;Agopian, Vatche G.
背景和目标 器官采购和移植网络最近批准了对超出米兰标准 (MC) 且接受局部治疗 (LRT) 降期 (DS) 的肝细胞癌 (HCC) 患者进行肝移植 (LT) 优先。我们评估了来自美国多中心 HCC 移植联盟（20 个中心，2002-2013 年）的 MC 以外 HCC 患者的 LT 后结局、降期预测因素以及 LRT 的影响。方法和结果比较 MC 内（n = 3,570）和 MC 外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) (n = 789) 降期 (DS, n = 465)、接受 LRT 治疗但未降期 (LRT-NoDS, n = 242) 或未治疗 (NoLRT-NoDS, n = 82)。与 DS（64.3% 和 59.5%）相比，MC 的 LT 后五年 OS 和 RFS 较高（71.3% 和 68.2%），NoDS 最低（n = 324；60.2% 和 53.8%；总体 P < 0.001）。与 NoDS 相比，DS 患者具有较高的 RFS（60% vs. 54%，P = 0.043）和较低的 5 年 HCC-R（18% vs. 32%，P < 0.001），并根据最大放射学肿瘤直径进行进一步分层（DS/5 cm 中的 5 年 HCC-R 为 15.5%，P < 0.001）。降期的多变量预测因素包括甲胎蛋白对 LRT 的反应、病理肿瘤数量和大小以及 >12 个月的等待时间。即使在控制了临床病理变量（风险比 [HR] = 2.33，P < 0.001）和治疗加权倾向匹配的逆概率（HR = 1.82，P < 0.001）后，LRT-NoDS 的 HCC-R 仍高于 NoLRT-NoDS（34.1% vs. 26.1%，P < 0.001）。 HCC 表现超出 MC，通过等待时间、甲胎蛋白对 LRT 的反应以及肿瘤负荷来预测成功的降期，并导致优异的 LT 后结果，证明了 LT 标准扩展的合理性。在 LRT-NoDS 患者中，与 NoLRT-NoDS 患者相比，HCC-R 较高，不能用临床病理学差异来解释，这表明 LRT 对肿瘤生物学较差的患者具有潜在的加重作用，值得进一步研究。
Background and Aims 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).Approach and Results 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, 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).Conclusions 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.