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. 2024 Oct 31:37:13641.
doi: 10.3389/ti.2024.13641. eCollection 2024.

Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study

Marianna Maspero  1   2 , Carlo Sposito  1   2 , Marco A Bongini  1 , Tommaso Cascella  3 , Maria Flores  1 , Marco Maccauro  4 , Carlo Chiesa  4 , Monica Niger  5 , Filippo Pietrantonio  5 , Giuseppe Leoncini  6 , Valentina Bellia  1 , Sherrie Bhoori  1 , Vincenzo Mazzaferro  1   2
Affiliations

Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study

Marianna Maspero et al. Transpl Int. .

Abstract

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.

Keywords: Yttrium-90; biliary tract cancers; downstaging; gemcitabine-cisplatin; tare.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Neoadjuvant combined systemic therapy and radioembolization (SYS-TARE) protocol for unresectable intrahepatic. iCC, intrahepatic cholangiocarcinoma; GemCis, gemcitabine + cisplatin; SD, stable disease; PR, partial response; CR, complete response; PD, progressive disease; MDT, multidisciplinary team; WL, waitlist; CT, chemotherapy. Second-line chemotherapy was indicated according to standard of care, preferably with targeted therapy if actionable mutations were present at next-generation sequencing analysis. Maintenance chemotherapy included additional cycles of GemCis until transplant or disease progression.
FIGURE 2
FIGURE 2
Flowchart summarizing treatment allocation and evolution of 13 unresectable mass-forming iCC, according to tumor response after combined chemotherapy and radioembolization.
FIGURE 3
FIGURE 3
Downstaging sequences of the 4 responding patients who underwent liver transplantation. GemCis, gemcitabine + cisplatin; C, cycles; SD, stable disease; TARE, transarterial radioembolization; ExLap, exploratory laparotomy/laparoscopy; PD, progressive disease; NED, no evidence of disease.
FIGURE 4
FIGURE 4
Case 3 of Table 2: radiological [(A), before therapy; (B), after SYS-TARE], ex vivo (C) and histological (D) appearance of hepatic vein encasement without intimal penetration.
FIGURE 5
FIGURE 5
Kaplan Meier curves of overall survival from completion of SYS-TARE (i.e., last TARE within protocol) for transplanted and non-transplanted patients.
See this image and copyright information in PMC

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