Gemcitabine and Cisplatin as Neo-Adjuvant for Cholangiocarcinoma Patients Prior to Liver Transplantation: Case-Series

Abstract

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.

Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision

“…The last decade witnessed a scientific revolutionof the transplant oncology field that provides an excellent option to treat patients with iCCA by liver transplant [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Two main scenarios are worth attention in the transplant perspective.…”

“…First, evidence supports liver transplantation (LT) in “very early” iCCA (in which the tumor isno more than 2 cm) arising in the context of hepatic cirrhosis and not amenable to liver resection because of poor liver function. A key study in 2016 reported lower recurrence and improved survival after LT in such patients compared to those with more advanced iCCAs [ 13 , 24 ]. Moreover, a recent multicentric experience in France has observed for patients with larger lesions (2–5 cm) a post-LT 5-year OS and RFS comparable to those of patients with tumors ≤2 cm, noting that differentiation rather than size correlated with tumor recurrence on multivariate analysis [ 25 ].…”

Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pretransplant Setting: A Case Report

“…Other risk factors include non-alcohol-associated steatohepatitis (NASH), or patients with chronic hepatitis B and C virus infection [ 2 , 3 , 4 ]. HCC comprises 75% of primary liver tumors with cholangiocarcinoma accounting for the remaining cases [ 1 , 5 , 6 , 7 ].…”

“…In the last decade, the transplant oncology field has been evolving and advances in locoregional and systemic therapies including immunotherapy have provided additional options for further exploration of neoadjuvant and adjuvant strategies to improve HCC resection rates [ 6 , 7 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. We report an interesting case of a patient with HCC who developed pseudo-progression followed by an excellent response with significant downstaging after neoadjuvant treatment with atezolizumab plus bevacizumab.…”

Timeline of FDA-Approved Targeted Therapy for Cholangiocarcinoma

“…Depending on the type of CCA and the locality of the disease, surgical resection remains a treatment option with long-term survival [ 20 ]. This includes liver transplantation which has treated hepatobiliary malignancies with significantly improved outcomes [ 21 , 22 , 23 , 24 ]. Unfortunately, CCA is often diagnosed at an advanced stage where surgical intervention will not be sufficient.…”