Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medicine, New York, New York.
Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York.
JAMA Surg. 2021 Jun 1;156(6):559-567. doi: 10.1001/jamasurg.2021.0954.
Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured.
To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020.
The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome.
Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0.
This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.
准确预测肝癌（HCC）患者肝移植后的复发是移植管理机构用于识别 HCC 患者候选资格的主要选择工具。尽管已经取得了进展，但很少有工具纳入肿瘤生物学特征的客观指标，导致包括复发率高的患者，排除了其他可能治愈的患者。
外部验证纽约/加利福尼亚（NYCA）评分，这是一种最近发表的美国多机构 HCC 选择工具，是第一个纳入动态甲胎蛋白反应（AFP-R）的模型，并将验证后的评分与目前公认的 HCC 选择工具，即米兰标准（MC）、法国 AFP（F-AFP）和 Metroticket 2.0 模型进行比较。
设计、地点和参与者：对 3 个美国、1 个加拿大和 4 个欧洲中心的 2236 例成人 HCC 患者前瞻性收集的数据库进行了回顾性多中心预后分析，这些患者于 2001 年 1 月 1 日至 2013 年 12 月 31 日接受了肝移植。AFP-R 作为最大和最终术前 AFP 水平之间的差异进行测量。Cox 比例风险回归和竞争风险回归分析检测无复发生存和总生存。接受者操作特征分析和净重新分类指数用于比较 NYCA 与 MC、F-AFP 和 Metroticket 2.0。数据分析于 2019 年 6 月至 2020 年 4 月进行。
主要研究结果是 5 年无复发生存率；总生存率为次要结果。
在 2236 例患者中，1808 例（80.9%）为男性；平均（SD）年龄为 58.3（7.96）岁。共有 545 例（24.4%）不符合 MC。NYCA 评分在竞争风险回归分析中被证明是有效的，准确地预测了无复发生存和总生存（NYCA 风险类别 5 年累积复发风险为低风险组为 9.5%，可接受风险组为 20.5%，高风险组为 40.5%；所有 P<0.001）。NYCA 还在特定中心水平上预测了无复发生存：453 例不符合 MC 的患者（83.1%），308 例不符合 F-AFP 的患者（69.2%），384 例不符合 Metroticket 2.0 的患者（76.1%）将被重新归类为 NYCA 低风险和可接受风险组（>75%的 5 年无复发生存率）。验证后的 NYCA 评分的 Harrell C 统计量为 0.66，而 MC 为 0.59，F-AFP 模型为 0.57（P<0.001）。NYCA 的净重新分类指数为 8.1 比 MC，12.9 比 F-AFP，10.1 比 Metroticket 2.0。
本研究似乎对外科验证 AFP-R 在 HCC 患者肝移植选择中的重要性进行了验证。AFP-R 是移植前可获得的真正客观的生物学特征之一。将 AFP-R 纳入选择标准可以安全地扩展 MC 和其他模型，为具有可接受肿瘤生物学特征的患者提供肝移植，否则这些患者将被拒绝潜在的治愈机会。
