Yoon Jun Sik, Sinn Dong Hyun, Lee Jeong-Hoon, Kim Hwi Young, Lee Cheol-Hyung, Kim Sun Woong, Lee Hyo Young, Nam Joon Yeul, Chang Young, Lee Yun Bin, Cho Eun Ju, Yu Su Jong, Kim Hyo-Cheol, Chung Jin Wook, Kim Yoon Jun, Yoon Jung-Hwan
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Korea.
Cancers (Basel). 2019 Nov 4;11(11):1721. doi: 10.3390/cancers11111721.
For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC.
This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149).
The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37-3.46, = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54-8.76, < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts.
The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.
对于肝细胞癌（HCC）患者，经动脉化疗栓塞术（TACE）难治性的定义仍存在争议，而这一定义可能会使患者成为全身治疗的候选对象。我们旨在推导并验证一种基于肿瘤标志物的算法，以定义中期HCC患者对TACE的难治性。
这项多队列研究纳入了初治中期HCC且接受TACE治疗的患者。我们使用TACE前后的模型来预测活体肝移植后肿瘤复发的总生存（OS）预测模型（即MoRAL评分=11×√维生素K缺乏诱导蛋白-II + 2×√甲胎蛋白），该模型已被证明能反映移植肝中HCC的肿瘤负荷和生物学侵袭性，数据来自一个训练队列（n = 193）。这些结果在一个独立的医院队列（来自两个大容量中心，n = 140）和一个韩国国家癌症登记样本队列（n = 149）中进行了外部验证。
首次TACE后MoRAL评分的变化（ΔMoRAL）是OS的独立预测因素（MoRAL升高与MoRAL未升高：校正风险比（HR）= 2.18，95%置信区间（CI）= 1.37 - 3.46，P = 0.001；中位OS = 18.8个月对37.8个月）。在基线MoRAL评分较高（≥89.5，第25百分位数及以上）的患者亚组中，ΔMoRAL的预后影响更为显著（MoRAL升高与MoRAL未升高：HR = 3.68，95% CI = 1.54 - 8.76，P < 0.001；中位OS = 9.9个月对37.4个月）。这些结果在外部验证队列中得到了重现。
首次TACE后的ΔMoRAL是一个简单客观的指标，可为中期HCC患者提供精确的预后评估。对于基线MoRAL评分较高（≥89.5）且首次TACE后MoRAL升高的患者，他们可能是全身治疗的候选对象，进行第二次TACE可能不会带来额外的生存获益。
