Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma

Background. Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but thei...

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Main Authors: Nadine Soliman, MD, Ashton A. Connor, MD, PhD, Ashish Saharia, MD, Sudha Kodali, MD, MSPH, Ahmed Elaileh, MD, Khush Patel, MD, MS, Samar Semaan, MD, Tamneet Basra, MD, David W. Victor, III, MD, Caroline J. Simon, MD, Yee Lee Cheah, MD, Mark J. Hobeika, MD, Constance M. Mobley, MD, PhD, Mukul Divatia, MD, Sadhna Dhingra, MD, Mary Schwartz, MD, Anaum Maqsood, MD, Kirk Heyne, MD, Maen Abdelrahim, MD, PhD, Milind Javle, MD, Jean-Nicolas Vauthey, MD, A. Osama Gaber, MD, R. Mark Ghobrial, MD, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2025-03-01
Series:Transplantation Direct
Online Access:http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001760
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author Nadine Soliman, MD
Ashton A. Connor, MD, PhD
Ashish Saharia, MD
Sudha Kodali, MD, MSPH
Ahmed Elaileh, MD
Khush Patel, MD, MS
Samar Semaan, MD
Tamneet Basra, MD
David W. Victor, III, MD
Caroline J. Simon, MD
Yee Lee Cheah, MD
Mark J. Hobeika, MD
Constance M. Mobley, MD, PhD
Mukul Divatia, MD
Sadhna Dhingra, MD
Mary Schwartz, MD
Anaum Maqsood, MD
Kirk Heyne, MD
Maen Abdelrahim, MD, PhD
Milind Javle, MD
Jean-Nicolas Vauthey, MD
A. Osama Gaber, MD
R. Mark Ghobrial, MD, PhD
author_facet Nadine Soliman, MD
Ashton A. Connor, MD, PhD
Ashish Saharia, MD
Sudha Kodali, MD, MSPH
Ahmed Elaileh, MD
Khush Patel, MD, MS
Samar Semaan, MD
Tamneet Basra, MD
David W. Victor, III, MD
Caroline J. Simon, MD
Yee Lee Cheah, MD
Mark J. Hobeika, MD
Constance M. Mobley, MD, PhD
Mukul Divatia, MD
Sadhna Dhingra, MD
Mary Schwartz, MD
Anaum Maqsood, MD
Kirk Heyne, MD
Maen Abdelrahim, MD, PhD
Milind Javle, MD
Jean-Nicolas Vauthey, MD
A. Osama Gaber, MD
R. Mark Ghobrial, MD, PhD
author_sort Nadine Soliman, MD
collection DOAJ
description Background. Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied. Methods. We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response. Results. During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53–68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98–405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen. Conclusions. Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.
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spelling doaj-art-5944494adc99487db0b39f747d156e5f2025-08-20T02:45:37ZengWolters KluwerTransplantation Direct2373-87312025-03-01113e176010.1097/TXD.0000000000001760202503000-00002Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar CholangiocarcinomaNadine Soliman, MD0Ashton A. Connor, MD, PhD1Ashish Saharia, MD2Sudha Kodali, MD, MSPH3Ahmed Elaileh, MD4Khush Patel, MD, MS5Samar Semaan, MD6Tamneet Basra, MD7David W. Victor, III, MD8Caroline J. Simon, MD9Yee Lee Cheah, MD10Mark J. Hobeika, MD11Constance M. Mobley, MD, PhD12Mukul Divatia, MD13Sadhna Dhingra, MD14Mary Schwartz, MD15Anaum Maqsood, MD16Kirk Heyne, MD17Maen Abdelrahim, MD, PhD18Milind Javle, MD19Jean-Nicolas Vauthey, MD20A. Osama Gaber, MD21R. Mark Ghobrial, MD, PhD221 Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.4 Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.4 Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX.4 Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.6 Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX.6 Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX.6 Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX.7 Division of Medical Oncology, Department of Medicine, Houston Methodist Hospital, Houston, TX.5 Department of Medicine, Weill Cornell Medical College, New York, NY.5 Department of Medicine, Weill Cornell Medical College, New York, NY.8 Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.9 Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.2 Department of Surgery, Houston Methodist Hospital, Houston, TX.Background. Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied. Methods. We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response. Results. During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53–68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98–405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen. Conclusions. Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001760
spellingShingle Nadine Soliman, MD
Ashton A. Connor, MD, PhD
Ashish Saharia, MD
Sudha Kodali, MD, MSPH
Ahmed Elaileh, MD
Khush Patel, MD, MS
Samar Semaan, MD
Tamneet Basra, MD
David W. Victor, III, MD
Caroline J. Simon, MD
Yee Lee Cheah, MD
Mark J. Hobeika, MD
Constance M. Mobley, MD, PhD
Mukul Divatia, MD
Sadhna Dhingra, MD
Mary Schwartz, MD
Anaum Maqsood, MD
Kirk Heyne, MD
Maen Abdelrahim, MD, PhD
Milind Javle, MD
Jean-Nicolas Vauthey, MD
A. Osama Gaber, MD
R. Mark Ghobrial, MD, PhD
Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
Transplantation Direct
title Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
title_full Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
title_fullStr Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
title_full_unstemmed Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
title_short Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
title_sort neoadjuvant multiagent systemic therapy approach to liver transplantation for perihilar cholangiocarcinoma
url http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001760
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