Joseph DiNorcia1, Sander S Florman2, Brandy Haydel2, Parissa Tabrizian2, Richard M Ruiz3, Goran B Klintmalm3, Srinath Senguttuvan3, David D Lee4, C Burcin Taner4, Elizabeth C Verna5, Karim J Halazun6, Maarouf Hoteit7, Matthew H Levine7, William C Chapman8, Neeta Vachharajani8, Federico Aucejo9, Mindie H Nguyen10, Marc L Melcher11, Amit D Tevar12, Abhinav Humar12, Constance Mobley13, Mark Ghobrial13, Trevor L Nydam14, Beth Amundsen15, James F Markmann15, Jennifer Berumen16, Alan W Hemming16, Alan N Langnas17, Carol A Carney17, Debra L Sudan18, Johnny C Hong19, Joohyun Kim19, Michael A Zimmerman19, Abbas Rana20, Michael L Kueht20, Christopher M Jones21, Thomas M Fishbein22, Daniela Markovic23, Ronald W Busuttil1, Vatche G Agopian1. 1. Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. 2. Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY. 3. Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 4. Department of Transplantation, Mayo Clinic, Jacksonville, FL. 5. New York-Presbyterian Hospital, Columbia University, New York, NY. 6. New York-Presbyterian Hospital, Weill Cornell, New York, NY. 7. Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA. 8. Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO. 9. Cleveland Clinic Foundation, Cleveland, OH. 10. Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA. 11. Department of Surgery, Stanford University, Palo Alto, CA. 12. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA. 13. Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX. 14. Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO. 15. Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 16. Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA. 17. Department of Surgery, University of Nebraska Medical Center, Omaha, NE. 18. Department of Surgery, Duke University Medical Center, Durham, NC. 19. Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI. 20. Department of Surgery, Baylor College of Medicine, Houston, TX. 21. Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY. 22. Medstar Georgetown Transplant Institute, Georgetown University, Washington, DC. 23. Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Abstract
OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.
OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPRpatients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.
Authors: Maria Del Pilar Bayona Molano; Lorena Garza; Genaro Selvaggi; Jay Vasani; Juan Carlos Barrera Gutierrez; Jason Salsamendi; Shivank Bhatia; Leopoldo Arosemena Journal: Clin Exp Hepatol Date: 2020-12-30
Authors: Danielle L Stolley; Anna Colleen Crouch; Aliçan Özkan; Erin H Seeley; Elizabeth M Whitley; Marissa Nichole Rylander; Erik N K Cressman Journal: Pharmaceutics Date: 2020-12-20 Impact factor: 6.321