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. Nguyen & 19 others Marc L. Melcher, Trevor L. Nydam, Constance Mobley, R. Mark Ghobrial, Beth Amundsen, James F. Markmann, Alan Norman 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

29 Citations (Scopus)

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

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Liver Transplantation
Hepatocellular Carcinoma
Transplants
Recurrence
Survival
Therapeutics
Neoplasms
Multivariate Analysis

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

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. / 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 Norman; 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.

In: Annals of Surgery, Vol. 266, No. 3, 01.09.2017, p. 525-535.

Research output: Contribution to journalArticle

Agopian, VG, Harlander-Locke, MP, Ruiz, RM, Klintmalm, GB, Senguttuvan, S, Florman, SS, Haydel, B, Hoteit, M, Levine, MH, Lee, DD, Taner, CB, Verna, EC, Halazun, KJ, Abdelmessih, R, Tevar, AD, Humar, A, Aucejo, F, Chapman, WC, Vachharajani, N, Nguyen, MH, Melcher, ML, Nydam, TL, Mobley, C, Ghobrial, RM, Amundsen, B, Markmann, JF, Langnas, AN, Carney, CA, Berumen, J, Hemming, AW, Sudan, DL, Hong, JC, Kim, J, Zimmerman, MA, Rana, A, Kueht, ML, Jones, CM, Fishbein, TM & Busuttil, RW 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, vol. 266, no. 3, pp. 525-535. https://doi.org/10.1097/SLA.0000000000002381
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 Norman ; 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. / 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. In: Annals of Surgery. 2017 ; Vol. 266, No. 3. pp. 525-535.
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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.",
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author = "Agopian, {Vatche G.} and Harlander-Locke, {Michael P.} and Ruiz, {Richard M.} and Klintmalm, {Goran B.} and Srinath Senguttuvan and Florman, {Sander S.} and Brandy Haydel and Maarouf Hoteit and Levine, {Matthew H.} and Lee, {David D.} and Taner, {C. Burcin} and Verna, {Elizabeth C.} and Halazun, {Karim J.} and Rita Abdelmessih and Tevar, {Amit D.} and Abhinav Humar and Federico Aucejo and Chapman, {William C.} and Neeta Vachharajani and Nguyen, {Mindie H.} and Melcher, {Marc L.} and Nydam, {Trevor L.} and Constance Mobley and Ghobrial, {R. Mark} and Beth Amundsen and Markmann, {James F.} and Langnas, {Alan Norman} and Carney, {Carol A.} and Jennifer Berumen and Hemming, {Alan W.} and Sudan, {Debra L.} and Hong, {Johnny C.} and Joohyun Kim and Zimmerman, {Michael A.} and Abbas Rana and Kueht, {Michael L.} and Jones, {Christopher M.} and Fishbein, {Thomas M.} and Busuttil, {Ronald W.}",
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TY - JOUR

T1 - Impact of Pretransplant Bridging Locoregional Therapy for Patients with Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation

T2 - Analysis of 3601 Patients from the US Multicenter HCC Transplant Consortium

AU - Agopian, Vatche G.

AU - Harlander-Locke, Michael P.

AU - Ruiz, Richard M.

AU - Klintmalm, Goran B.

AU - Senguttuvan, Srinath

AU - Florman, Sander S.

AU - Haydel, Brandy

AU - Hoteit, Maarouf

AU - Levine, Matthew H.

AU - Lee, David D.

AU - Taner, C. Burcin

AU - Verna, Elizabeth C.

AU - Halazun, Karim J.

AU - Abdelmessih, Rita

AU - Tevar, Amit D.

AU - Humar, Abhinav

AU - Aucejo, Federico

AU - Chapman, William C.

AU - Vachharajani, Neeta

AU - Nguyen, Mindie H.

AU - Melcher, Marc L.

AU - Nydam, Trevor L.

AU - Mobley, Constance

AU - Ghobrial, R. Mark

AU - Amundsen, Beth

AU - Markmann, James F.

AU - Langnas, Alan Norman

AU - Carney, Carol A.

AU - Berumen, Jennifer

AU - Hemming, Alan W.

AU - Sudan, Debra L.

AU - Hong, Johnny C.

AU - Kim, Joohyun

AU - Zimmerman, Michael A.

AU - Rana, Abbas

AU - Kueht, Michael L.

AU - Jones, Christopher M.

AU - Fishbein, Thomas M.

AU - Busuttil, Ronald W.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - HCC recurrence

KW - hepatocellular carcinoma

KW - liver transplantation

KW - locoregional therapy

KW - recurrence-free survival

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DO - 10.1097/SLA.0000000000002381

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VL - 266

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JO - Annals of Surgery

JF - Annals of Surgery

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