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Multicenter Study
. 2023 Mar 7;7(2):zrad025.
doi: 10.1093/bjsopen/zrad025.

Role of neoadjuvant chemoradiotherapy in liver transplantation for unresectable perihilar cholangiocarcinoma: multicentre, retrospective cohort study

Frederik J H Hoogwater  1 , Hendrien Kuipers  1 , Vincent E de Meijer  1 , Charlotte Maulat  2 , Fabrice Muscari  2 , Wojciech G Polak  3 , Bart van Hoek  4 , Caroline Jézéquel  5 , Ian P J Alwayn  6 , Jan N M Ijzermans  3 , Kayvan Mohkam  7 , Jean-Yves Mabrut  7 , Frederike G I Van Vilsteren  8 , Jean-Philippe Adam  9 , Laurence Chiche  9 , Alexandre Chebaro  10 , Emmanuel Boleslawski  10 , Jeroen Dubbeld  6 , Sarwa Darwish Murad  11 , Michel Rayar  12   13 , Robert J Porte  1
Affiliations
Multicenter Study

Role of neoadjuvant chemoradiotherapy in liver transplantation for unresectable perihilar cholangiocarcinoma: multicentre, retrospective cohort study

Frederik J H Hoogwater et al. BJS Open. .

Abstract

Background: The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy.

Methods: This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence.

Results: Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044).

Conclusion: In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.

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Figures

Fig. 1
Fig. 1
Kaplan–Meier curves of time to recurrence after liver transplantation for unresectable perihilar cholangiocarcinoma The No-NAT group included only patients who did not receive neoadjuvant chemoradiation therapy with confirmed malignancy. The NAT group included patients who did receive neoadjuvant chemoradiation therapy. HR, hazards ratio; c.i., confidence interval; NAT, neoadjuvant therapy.
Fig. 2
Fig. 2
Kaplan–Meier curves of overall patient survival after liver transplantation for unresectable perihilar cholangiocarcinoma The No-NAT group included patients who did not receive neoadjuvant chemoradiation therapy. The NAT group included patients who did receive neoadjuvant chemoradiation therapy. HR, hazards ratio; NAT, neoadjuvant therapy.
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