Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series

Keri E Lunsford, Milind Javle, Kirk Heyne, Rachna T Shroff, Reham Abdel-Wahab, Nakul Gupta, Constance M Mobley, Ashish Saharia, David W Victor, Duc T Nguyen, Edward A Graviss, Ahmed O Kaseb, Robert S McFadden, Thomas A Aloia, Claudius Conrad, Xian C Li, Howard P Monsour, A Osama Gaber, Jean-Nicolas Vauthey, R Mark GhobrialMethodist–MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC)

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy.

METHODS: In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017.

FINDINGS: Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4).

INTERPRETATION: Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation.

FUNDING: None.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalThe Lancet Gastroenterology and Hepatology
Volume3
Issue number5
Early online dateMar 13 2018
DOIs
StatePublished - May 2018

Keywords

  • Journal Article
  • Bile Duct Neoplasms/diagnostic imaging
  • Recurrence
  • Prospective Studies
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Kaplan-Meier Estimate
  • Male
  • Cholangiocarcinoma/diagnostic imaging
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Radiography
  • Disease-Free Survival
  • Adult
  • Female
  • Neoadjuvant Therapy
  • Chemotherapy, Adjuvant
  • Liver Transplantation/adverse effects
  • Mutation
  • Postoperative Complications

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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    Lunsford, K. E., Javle, M., Heyne, K., Shroff, R. T., Abdel-Wahab, R., Gupta, N., Mobley, C. M., Saharia, A., Victor, D. W., Nguyen, D. T., Graviss, E. A., Kaseb, A. O., McFadden, R. S., Aloia, T. A., Conrad, C., Li, X. C., Monsour, H. P., Gaber, A. O., Vauthey, J-N., ... Methodist–MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC) (2018). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. The Lancet Gastroenterology and Hepatology, 3(5), 337-348. https://doi.org/10.1016/S2468-1253(18)30045-1