在 SiLVER 随机临床试验中验证 R3-AFP 模型对肝移植后 HCC 复发的风险预测。

IF 4.7 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Federico Piñero, Quirino Lai, Charlotte Costentin, Helena Degroote, Andreas Schnitzbauer, Edward K Geissler, Christophe Duvoux
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引用次数: 0

摘要

用于评估肝移植(LT)后肝细胞癌(HCC)复发情况的外植体模型是指导肝移植后筛查和免疫抑制调整的金标准。将甲胎蛋白(AFP)水平纳入这些模型(如新型 R3-AFP 评分)可显著提高风险分层能力。然而,这些模型必须经过高证据数据的验证。因此,本研究的目的是在随机临床试验中验证 R3-AFP 评分。我们分析了两臂 SiLVER 试验(NCT00355862)中的意向治疗(ITT)人群,该试验比较了基于钙神经蛋白(CNI-A 组)和基于哺乳动物雷帕霉素靶抑制剂(mTOR)(西罗莫司-B 组)的免疫抑制治疗 LT 后 HCC 复发。竞争风险分析估算了次危险比 (SHR),并对判别功能和校准进行了测试。ITT分析共纳入508名患者(A组,n=256;B组,n=252)。R3-AFP 评分分布如下42.6%为低风险组(n=216),35.7%为中风险组(n=181),19.5%为高风险组(n=99),2.2%为极高风险组(n=11)。R3-AFP 评分有效地对 HCC 复发风险进行了分层,每个分层的风险都在增加。R3-AFP 模型的校准效果明显优于其他基于外植体的模型(米兰模型、Up-to-7 模型和 RETREAT 模型),而辨别力[0.75 (95% CI 0.69;0.81)]则优于这些模型,RETREAT 模型除外(P=0.49)。亚组分析显示,mTOR 组的辨别力低于 CNI 组(P=0.048)。总之,R3-AFP评分利用高质量的循证数据准确预测了HCC复发,但在mTOR免疫抑制下表现出较低的性能。这凸显了进一步研究评估监测计划和辅助治疗方案的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Validation of the R3-AFP model for risk prediction of HCC recurrence after liver transplantation in the SiLVER randomized clinical trial.

Explant-based models for assessing HCC recurrence after liver transplantation serve as the gold standard, guiding post-liver transplantation screening and immunosuppression adjustment. Incorporating alpha-fetoprotein (AFP) levels into these models, such as the novel R3-AFP score, has notably enhanced risk stratification. However, validation of these models in high-evidence data is mandatory. Therefore, the aim of the present research was to validate the R3-AFP score in a randomized clinical trial. We analyzed the intention-to-treat population from the 2-arm SiLVER trial (NCT00355862), comparing calcineurin-based ([calcineurin inhibitors]-Group A) versus mammalian target of rapamycin inhibitors-based (sirolimus-Group B) immunosuppression for post-liver transplantation HCC recurrence. Competing risk analysis estimated sub-hazard ratios, with testing of discriminant function and calibration. Overall, 508 patients from the intention-to-treat analysis were included (Group A, n = 256; Group B, n = 252). The R3-AFP score distribution was as follows: 42.6% low-risk (n = 216), 35.7% intermediate-risk (n = 181), 19.5% high-risk (n = 99), and 2.2% very-high-risk (n = 11) groups. The R3-AFP score effectively stratified HCC recurrence risk, with increasing risk for each stratum. Calibration of the R3-AFP model significantly outperformed other explant-based models (Milan, Up-to-7, and RETREAT), whereas discrimination power (0.75 [95% CI: 0.69; 0.81]) surpassed these models, except for the RETREAT model ( p = 0.49). Subgroup analysis showed lower discrimination power in the mammalian target of rapamycin group versus the calcineurin inhibitors group ( p = 0.048). In conclusion, the R3-AFP score accurately predicted HCC recurrence using high-quality evidence-based data, exhibiting reduced performance under mammalian target of rapamycin immunosuppression. This highlights the need for further research to evaluate surveillance schedules and adjuvant regimens.

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来源期刊
Liver Transplantation
Liver Transplantation 医学-外科
CiteScore
7.40
自引率
6.50%
发文量
254
审稿时长
3-8 weeks
期刊介绍: Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AASLD, Liver Transplantation delivers current, peer-reviewed articles on liver transplantation, liver surgery, and chronic liver disease — the information necessary to keep abreast of this evolving specialty.
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