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

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

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish
Pages (from-to)525-535
Number of pages11
JournalAnnals of surgery
Volume266
Issue number3
DOIs
StatePublished - Sep 1 2017

Keywords

  • HCC recurrence
  • hepatocellular carcinoma
  • liver transplantation
  • locoregional therapy
  • recurrence-free survival

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    Agopian, V. G., Harlander-Locke, M. P., Ruiz, R. M., Klintmalm, G. B., Senguttuvan, S., Florman, S. S., Haydel, B., Hoteit, M., Levine, M. H., Lee, D. D., Taner, C. B., Verna, E. C., Halazun, K. J., Abdelmessih, R., Tevar, A. D., Humar, A., Aucejo, F., Chapman, W. C., Vachharajani, N., ... Busuttil, R. W. (2017). 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. Annals of surgery, 266(3), 525-535. https://doi.org/10.1097/SLA.0000000000002381