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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 Agopian1, Michael P Harlander-Locke1, Richard M Ruiz2, Goran B Klintmalm2, Sander S Florman3, Brandy Haydel3, Maarouf Hoteit4, David D Lee5, C. Burcin Taner5, Elizabeth C Verna6, Karim J Halazun7, Amit D Tevar8, Federico Aucejo9, William C Chapman10, Neeta Vachharajani10, Marc L Melcher11, Mindie H Nguyen11, Trevor L Nydam12, Constance Mobley13, Mark R Ghobrial13, Beth M Amundsen14, James F Markmann14, Alan N Langnas15, Carol A Carney15, Jennifer Berumen16, Alan W Hemming16, Debra L Sudan17, Johnny C Hong18, Joohyun Kim18, Michael A Zimmerman18, Abbas Rana19, Michael L Kueht19, Christopher M Jones20, Thomas M Fishbein*21, Ronald W Busuttil1
1Dumont UCLA Transplant Center, University of California, Los Angeles, Los Angeles, CA;2Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX;3Icahn School of Medicine at Mount Sinai, New York, NY;4Penn Transplant Institute, University of Pennsylvania School of Medicine, Philadelphia, PA;5Department of Transplantation, Mayo Clinic, Jacksonville, FL;6New York Presbyterian Hospital, Columbia University Medical Center, New York, NY;7New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY;8Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA;9Cleveland Clinic Foundation, Cleveland, OH;10Washington University School of Medicine, St. Louis, MO;11Stanford University Medical Center, Palo Alto, CA;12Division of Transplant, University of Colorado School of Medicine, Denver, CO;13Houston Methodist Hospital, Houston, TX;14Division of Transplant Surgery, Massachussetts General Hospital, Harvard Medical School, Boston, MA;15Section of Transplantation, University of Nebraska Medical Center, Omaha, NE;16Division of Transplantation, Department of Surgery, University of California, San Diego, San Diego, CA;17Division of Abdominal Transplant Surgery, Department of Surgery, Duke University Medical Center, Durham, NC;18Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI;19Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX;20Division of Transplant Surgery, Department of Surgery, University of Louisville School of Medicine, Louisville, KY;21Medstar Georgetown Transplant Institute, Georgetown University, Washington, DC

OBJECTIVE(S): Pretransplant locoregional therapy (LRT) mitigates tumor progression and waitlist dropout in hepatocellular carcinoma (HCC) patients within Milan Criteria(MC) listed for liver transplantation(LT). We sought to evaluate the effect of LRT on post-LT recurrence and survival, where data remains limited.
METHODS: Recurrence-free survival and post-LT recurrence were compared among MC patients with and without bridging LRT utilizing competing risk Cox-regression in consecutive patients from 20 US centers (2002-2013).
RESULTS: Of 3601 MC LT recipients, 2854 receiving LRT(79.3%) had similar 1-, 3-, and 5-year recurrence-free survival and post-LT recurrence compared to the 747(20.7%) without LRT, with increasing treatment number and unfavorable waitlist alphafetorotein (AFP) trend significantly predicting post-LT recurrence (Figure). Treated patients achieving complete pathologic response (cPR)(n=702,19.5%) had significantly lower post-LT recurrence compared to patients without cPR (n=2082, 57.8%; 5.3% vs 13.1%, P<0.001). In multivariable analysis controlling for pre-LT variables, LRT number but not modality significantly affected post-LT recurrence (Table).
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 AFP response to LRT predict post-LT recurrence, and serve as a surrogate for more aggressive tumor biology.
Multivariate Analysis of LRT Number and Modality on Post-LT Recurrence Controlling for AFP and NLR
Controlled Variable kept constantVariableHazard Ratio95% CIP-value
TACE2LRT vs 11.460.99-2.130.053
3+ LRT vs 12.581.75-3.79<0.001
Ablation2 LRT vs 10.890.3-2.590.826
3+ LRT vs 15.62.3-13.5<0.001
TACE and Ablation3+ LRT vs 21.970.97-4.000.060
1 TreatmentAblation vs TACE1.050.67-1.640.833
2 TreatmentsAblation vs TACE0.640.22-1.820.401
Ablation+TACE vs TACE0.840.44-1.590.587
3+ TreatmentsAblation vs TACE2.280.97-5.360.059

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