JHEP reports : innovation in hepatology · 2026
Liver transplantation in unresectable intrahepatic cholangiocarcinoma following neoadjuvant chemotherapy and SIRT.
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Giguet Baptiste, Artru Florent, Jeddou Heithem, Houssel-Debry Pauline, Jegonday Marc-Antoine, Coirier Valentin, Jezequel Caroline, Chebaro Alexandre, Robin Fabien, Boudjema Karim, Rolland Yan, Garin Etienne, Beuzit Luc, Turlin Bruno, Bardou-Jacquet Edouard, Edeline Julien, Uguen Thomas
Аннотация
BACKGROUND & AIMS: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis, with limited curative options. Chemotherapy combined with selective internal radiation therapy (SIRT) has shown promising results in tumor response and survival. We evaluated liver transplantation (LT) outcomes following this neoadjuvant approach in patients with liver-limited iCCA in our center.
METHOD: We retrospectively included all patients who underwent LT in the Rennes University Hospital for unresectable, locally advanced iCCA following neoadjuvant treatment with a combination of chemotherapy and SIRT.
RESULTS: Six patients underwent transplantation between 2010 and 2024. The median timeframe from diagnosis to listing was 351 days (IQR 250-558 days). The median time from listing to LT was 114 days (44-192 days). Age was 50.7 years (39.9-59.3 years) with a sex ratio of 1:1. The initial total tumor size was 100 mm (65-115 mm), with one tumoral lesion (1-1). Neoadjuvant treatment consisted of a gemcitabine-cisplatin regimen in four of six patients (66.7%), while one patient received cisplatin combined with 5-fluorouracil. The median follow-up was 4.9 years (1.8-8.8 years). The median length of hospitalization following LT was 12 days (10-20 days). Five-year overall survival was 100%, while 5-year progression-free survival was 44.4% (95% CI 8.9-88.0%) with three patients who experienced iCCA recurrence on Days 573, 577, and 1,180 after LT. No patient has yet died from tumor progression.
CONCLUSIONS: This study presents one of the first series of unresectable iCCA cases treated with a neoadjuvant combination of SIRT and chemotherapy. Very selected patients (six patients over 15 years) who underwent LT demonstrated high long-term survival rates and an acceptable recurrence rate, even in the presence of large tumor sizes. Prospective trials evaluating this neoadjuvant combination are awaited.
IMPACT AND IMPLICATIONS: Liver transplantation is not currently considered a standard therapeutic option for patients with unresectable, liver-limited intrahepatic cholangiocarcinoma because of historically poor outcomes. This study provides a scientific rationale for reconsidering transplantation in a highly selected subgroup of patients who achieve sustained disease control after neoadjuvant chemotherapy combined with selective internal radiation therapy. The results are particularly relevant for transplant hepatologists, oncologists, and surgeons, as they suggest that treatment response and prolonged disease stability may better predict post-transplant outcomes than tumor size alone. Clinically, these findings support a multidisciplinary, response-based selection strategy with a 'test-of-time' approach, while acknowledging the small sample size and retrospective design, and highlight the need for prospective studies and structured allocation frameworks to safely expand this approach.
METHOD: We retrospectively included all patients who underwent LT in the Rennes University Hospital for unresectable, locally advanced iCCA following neoadjuvant treatment with a combination of chemotherapy and SIRT.
RESULTS: Six patients underwent transplantation between 2010 and 2024. The median timeframe from diagnosis to listing was 351 days (IQR 250-558 days). The median time from listing to LT was 114 days (44-192 days). Age was 50.7 years (39.9-59.3 years) with a sex ratio of 1:1. The initial total tumor size was 100 mm (65-115 mm), with one tumoral lesion (1-1). Neoadjuvant treatment consisted of a gemcitabine-cisplatin regimen in four of six patients (66.7%), while one patient received cisplatin combined with 5-fluorouracil. The median follow-up was 4.9 years (1.8-8.8 years). The median length of hospitalization following LT was 12 days (10-20 days). Five-year overall survival was 100%, while 5-year progression-free survival was 44.4% (95% CI 8.9-88.0%) with three patients who experienced iCCA recurrence on Days 573, 577, and 1,180 after LT. No patient has yet died from tumor progression.
CONCLUSIONS: This study presents one of the first series of unresectable iCCA cases treated with a neoadjuvant combination of SIRT and chemotherapy. Very selected patients (six patients over 15 years) who underwent LT demonstrated high long-term survival rates and an acceptable recurrence rate, even in the presence of large tumor sizes. Prospective trials evaluating this neoadjuvant combination are awaited.
IMPACT AND IMPLICATIONS: Liver transplantation is not currently considered a standard therapeutic option for patients with unresectable, liver-limited intrahepatic cholangiocarcinoma because of historically poor outcomes. This study provides a scientific rationale for reconsidering transplantation in a highly selected subgroup of patients who achieve sustained disease control after neoadjuvant chemotherapy combined with selective internal radiation therapy. The results are particularly relevant for transplant hepatologists, oncologists, and surgeons, as they suggest that treatment response and prolonged disease stability may better predict post-transplant outcomes than tumor size alone. Clinically, these findings support a multidisciplinary, response-based selection strategy with a 'test-of-time' approach, while acknowledging the small sample size and retrospective design, and highlight the need for prospective studies and structured allocation frameworks to safely expand this approach.