Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma

Abstract

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n ‫؍‬ 6), subsequent development of malignant ascites (n ‫؍‬ 1), or death from intrahepatic biliary sepsis (n ‫؍‬ 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients G 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma. (Liver Transpl 2000;6:309-316.)

Liver transplantation for cholangiocellular carcinoma: Analysis of a single-center experience and review of the literature

“…Two such investigations using different regimens of adjuvant and neoadjuvant chemoirradiation have been published to date. 24,28 In the earlier study, Goldstein et al 24 from Baylor University Medical Center administered an adjuvant chemoirradiation protocol consisting of regional radiotherapy and systemic 5-fluorouracil to 14 patients with CCC undergoing LT. Although toxicities were limited, poor disease-free survival led the investigators to conclude that this regimen offered little benefit.…”

“…However, the allocation of limited donor organs to this patient population has been extremely controversial. In the literature, several centers reported the use of LT for patients with CCC 10,[17][18][19][20][21][22][23][24][25][26][27][28] with limited results because of high recurrence rates. The purpose of this study is to retrospectively review our experience with LT for patients with IH-CCC and EH-CCC to determine prognostic variables that may impact on patient selection and outcome.…”

The perspective of liver transplantation for cholangiocarcinoma

“…[1][2][3][4][5][6] Other attempts have included adjuvant and neoadjuvant treatment protocols applying radiotherapy with or without chemotherapy. [7][8][9][10][11] Overlooking more than a decade of experience with these different attempts, the Mayo Clinic group has emerged as the most successful among these pioneers. Their results with liver transplantation and neoadjuvant radiochemotherapy for patients suffering from cholangiocarcinoma are comparable to results of liver transplantation for early hepatocellular carcinoma as well as other chronic liver diseases.…”

“…Their results with liver transplantation and neoadjuvant radiochemotherapy for patients suffering from cholangiocarcinoma are comparable to results of liver transplantation for early hepatocellular carcinoma as well as other chronic liver diseases. 7,12,13 A 5-year-survival rate of 83% is an outstanding and unprecedented figure that a few years ago would not have been considered to be a realistic goal in any type of treatment for cholangiocarcinoma.…”

Hilar Cholangiocarcinoma: No Longer Hopeless

“…We proposed that liver transplantation-after careful selection of patients with early stage disease, neoadjuvant therapy, and operative staging-could achieve reasonable survival. We reported our initial results with treatment of 19 patients between 1993 and 2000 [3].…”