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移植前局部区域治疗对肝细胞癌的完全病理缓解定义了肝移植后的癌症治愈：对 501 例连续治疗患者的分析。

Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients.

机构信息

*Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, Los Angeles, CA; and Departments of †Radiology, and ‡Biomathematics, David Geffen School of Medicine at University of California, Los Angeles, CA.

出版信息

Ann Surg. 2015 Sep;262(3):536-45; discussion 543-5. doi: 10.1097/SLA.0000000000001384.

DOI:10.1097/SLA.0000000000001384

PMID:26258323

Abstract

OBJECTIVES

To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT).

BACKGROUND

Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis.

METHODS

Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified.

RESULTS

Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence-free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75).

CONCLUSIONS

Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT strategies to maximize cPR would enhance posttransplant cancer outcomes.

摘要

目的

评估接受肝移植（LT）前局部区域治疗（LRT）的肝细胞癌（HCC）患者完全病理缓解（cPR）的发生率、效果和预测因素。

背景

尽管 HCC 患者的肿瘤进展、等待名单脱落和移植后复发的风险不同，但符合条件的 HCC 患者接受的终末期肝病模型（MELD）评分相同。LT 前的 LRT 通过诱导肿瘤坏死来降低这些风险。

方法

对 1994 年至 2013 年接受 LT 前 LRT 的 126 例 HCC 患者（cPR 组）和 375 例无 cPR 患者（无 cPR 组）进行了比较。确定 cPR 的多变量预测因素。

结果

501 例患者中，1 例、2 例和 3 例或更多例 LRT 治疗的患者分别为 272 例、148 例和 81 例。1、3 和 5 年的总体生存率、无复发生存率和疾病特异性生存率分别为 86%、71%、63%；84%、67%、60%；97%、90%、87%。与无 cPR 患者相比，cPR 患者的实验室 MELD 评分、移植前甲胎蛋白和累积肿瘤直径较低；更有可能有 1 个病灶、米兰/加州大学旧金山分校（UCSF）标准内的肿瘤、包括消融在内的 LRT 和对 LRT 的有利肿瘤反应；并且具有更好的 1、3 和 5 年无复发生存率（92%、79%和 73% vs 81%、63%和 56%；P=0.006）和疾病特异性生存率（100%、100%和 99% vs 96%、89%和 86%；P<0.001），仅有 1 例癌症特异性死亡和较少的复发（2.4% vs 15.2%；P<0.001）。cPR 的多变量预测因素包括 LRT 后影像学/甲胎蛋白肿瘤反应良好、LRT 至 LT 的时间间隔较长以及 MELD 评分和最大肿瘤直径较低（C 统计量 0.75）。