Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma

Официальное название

Living Donor Liver Transplantation for Neoadjuvant Treated, Unresectable Intrahepatic Cholangiocarcinoma

Обзор

This study is supposed to make liver transplantation available for treatment in well selected patients suffering from non-resectable intrahepatic cholangiocarcinoma. Donor organ shortage is currently the main problem for organ transplantation world-wide. Thus, the particular indication "non-resectable intrahepatic cholangiocarcinoma" is currently excluded in terms of transplantation. Given those circumstances, transplantation via living donation might be the best option. This procedure does not reduce the deceased donor organ supply because living donation is the primary treatment option in these patients (not subsidiary).

Подробное описание

Intrahepatic cholangiocarcinoma (iCCA) is classified among primary liver tumors and has demonstrated a consistently increasing incidence in recent years. Due to the poor long-term survival rates reported in older studies, liver transplantation continues to be a contraindication in the curative treatment of iCCA. The persistent shortage of organs also necessitates that each new indication for transplantation be carefully evaluated and critically scrutinized. Currently, partial resection remains the preferred treatment modality, although at diagnosis, only approximately 20% of cases are amenable to this approach. Post-partial resection, the five-year survival rate is observed to be between 20-34%. In cases of irresectability, palliative chemotherapy often remains the only option, typically associated with a poor prognosis. Numerous studies have demonstrated that long-term outcomes following liver transplantation for iCCA have evolved and improved over the years. In a meta-analysis by Ziogas et al., data from a total of 18 studies (involving 355 patients) and one registry study (385 patients) were analyzed. The pooled 1-, 3-, and 5-year survival rates were 75%, 56%, and 42%, respectively. Meanwhile, the pooled 1-, 3-, and 5-year recurrence-free survival rates were 70%, 49%, and 38%, with an overall recurrence rate of 43%. A potential reason for this marked improvement may be attributed to the introduction of neoadjuvant therapy. Studies by Hu et al. and Lunsford et al. have demonstrated that the utilization of neoadjuvant therapy is associated with significantly improved survival outcomes. The study aims to conduct a prospective, non-randomized study (LIVINCA) to further explore the effects of living-donor liver transplantation in the treatment of unresectable neoadjuvant treated (chemotherapy AND selective internal radiotherapy) intrahepatic cholangiocarcinoma.

Вмешательства

• Процедура Living donor liver transplantation
  Liver transplantation from living donor donation (SII/III as left-lateral donation during a "two stage"-procedure or left lobe donation or right lobe donation) in patients with unresectable intrahepatic cholangiocarcinoma.

Первичные конечные точки

• Five year overall survival [Срок оценки: Five years]

Вторичные конечные точки (2)

• Recurrence-free survival [Срок оценки: Five years]
• Donor and Recipient morbidity [Срок оценки: Five years]

Критерии участия

Критерии включения

• non-resectable intrahepatic cholangiocarcinoma (either for localization / distribution of the carcinoma or for estimated function of the liver in case of liver fibrosis / cirrhosis)
• biopsy proven grading G1 / G2
• in case of mixed hepatocellular carcinoma / cholangiocarcinoma, the cholangiocarcinoma also must have a grading of G1 / G2
• response to chemotherapy in terms of stable or regressive disease (imaging studies, tumor marker CA19-9, any chemotherapy regime allowed, a local-ablative therapy in means of a SIRT is mandatory
• peritoneal carcinosis / extrahepatic spread ruled out in PET-CT and/or MRT/CT and, at latest, during exploration
• age ≥ 18
• blood-group compatible living donor available
• in female patients: negative pregnancy test
• written informed consent before study enrolment of donor and recipient (all other procedures are clinical routine procedures in the management of these patients)

Критерии исключения

• extrahepatic tumor/metastases
• G3 tumors
• progress under neoadjuvant treatment according to the RECIST-criteria
• pregnancy or breastfeeding
• patients unwilling to consent to saving and propagation of pseudonymized medical data for study reasons
• general contraindications for liver transplantation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma. Liver Transpl. 2018 Feb;24(2):294-303. doi: 10.1002/lt.24955. PMID 29024405
• Ziogas IA, Giannis D, Economopoulos KP, Hayat MH, Montenovo MI, Matsuoka LK, Alexopoulos SP. Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates. Transplantation. 2021 Oct 1;105(10):2263-2271. doi: 10.1097/TP.0000000000003539. PMID 33196623
• Chan KM, Tsai CY, Yeh CN, Yeh TS, Lee WC, Jan YY, Chen MF. Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence. BMC Gastroenterol. 2018 Dec 4;18(1):180. doi: 10.1186/s12876-018-0912-x. PMID 30514231
• Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, Mobley CM, Saharia A, Victor DW, Nguyen DT, Graviss EA, Kaseb AO, McFadden RS, Aloia TA, Conrad C, Li XC, Monsour HP, Gaber AO, Vauthey JN, Ghobrial RM; Methodist-MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant PMID 29548617
• McMillan RR, Javle M, Kodali S, Saharia A, Mobley C, Heyne K, Hobeika MJ, Lunsford KE, Victor DW 3rd, Shetty A, McFadden RS, Abdelrahim M, Kaseb A, Divatia M, Yu N, Nolte Fong J, Moore LW, Nguyen DT, Graviss EA, Gaber AO, Vauthey JN, Ghobrial RM. Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma. Am J Transplant. 2022 Mar;22(3):823-832. doi PMID 34856069

Идентификаторы

NCT: NCT06539377 · 2024-3430-BO

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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