米兰标准内肝细胞癌患者肝移植前桥接局部区域治疗的影响：来自美国多中心肝癌移植联盟的3601例患者分析

Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium.

作者信息

Agopian Vatche G, Harlander-Locke Michael P, Ruiz Richard M, Klintmalm Goran B, Senguttuvan Srinath, Florman Sander S, Haydel Brandy, Hoteit Maarouf, Levine Matthew H, Lee David D, Taner C Burcin, Verna Elizabeth C, Halazun Karim J, Abdelmessih Rita, Tevar Amit D, Humar Abhinav, Aucejo Federico, Chapman William C, Vachharajani Neeta, Nguyen Mindie H, Melcher Marc L, Nydam Trevor L, Mobley Constance, Ghobrial R Mark, Amundsen Beth, Markmann James F, Langnas Alan N, Carney Carol A, Berumen Jennifer, Hemming Alan W, Sudan Debra L, Hong Johnny C, Kim Joohyun, Zimmerman Michael A, Rana Abbas, Kueht Michael L, Jones Christopher M, Fishbein Thomas M, Busuttil Ronald W

机构信息

*Dumont-UCLA Liver Transplant and Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA †Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX ‡Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY §Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA ¶Department of Transplantation, Mayo Clinic, Jacksonville, FL ||New York Presbyterian Hospital, Columbia University, New York, NY **New York Presbyterian Hospital, Weill Cornell, New York, NY ††Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA ‡‡Cleveland Clinic Foundation, Cleveland, OH §§Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO ¶¶Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA ||||Department of Surgery, Stanford University, Palo Alto, CA ***Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO †††Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX ‡‡‡Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA §§§Department of Surgery, University of Nebraska Medical Center, Omaha, NE ¶¶¶Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA ||||||Department of Surgery, Duke University Medical Center; Durham, NC ****Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI ††††Department of Surgery, Baylor College of Medicine, Houston, TX ‡‡‡‡Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY §§§§Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia.

出版信息

Ann Surg. 2017 Sep;266(3):525-535. doi: 10.1097/SLA.0000000000002381.

DOI:10.1097/SLA.0000000000002381

PMID:28654545

Abstract

OBJECTIVE

To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).

SUMMARY BACKGROUND DATA

Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.

METHODS

Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).

RESULTS

Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).

CONCLUSIONS

Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

摘要

目的

评估移植前桥接局部区域治疗（LRT）对符合米兰标准（MC）的肝细胞癌（HCC）患者肝移植（LT）后复发及生存的影响。

总结背景数据

LT前LRT可减轻MC内HCC患者的肿瘤进展及等待名单上的退出率，但关于其对LT后复发及生存影响的数据仍然有限。

方法

利用竞争风险Cox回归对来自美国20个中心（2002 - 2013年）的3601例MC患者进行比较，这些患者接受或未接受桥接LRT。

结果

与747例未接受LRT的LT受者相比，2854例接受LRT的患者1年、3年和5年无复发生存率相似（89%、77%、68%对85%、75%、68%；P = 0.490），LT后5年复发率也相似（11.2%对10.1%；P = 0.474）。LRT次数增加[3次LRT：风险比（HR）2.1，P < 0.001；4次及以上LRT：HR 2.5，P < 0.001]以及等待名单上甲胎蛋白呈不利趋势显著预测LT后复发，而LRT方式则不然。与未治疗患者（69%；P = 0.010；HR 1.0）和未达到完全病理缓解（cPR）的治疗患者（67%；P = 0.010；HR 1.31，P = 0.039）相比，达到cPR的治疗患者5年无复发生存率更高（72%），LT后复发率更低（HR 0.52，P < 0.001），在多变量分析中，在控制移植前和病理因素的情况下，未达到cPR的治疗患者与未治疗患者相比复发增加（HR 1.32，P = 0.044）。