From Palliation to Cure: Liver Transplantation in Oncologic Practice by Dr. George Therapondos, MD

Overview

This lecture by Dr. George Therapondos explores the expanding role of liver transplantation in oncologic practice, focusing on cholangiocarcinoma subtypes and colorectal liver metastases, with emphasis on living donor liver transplantation as the preferred approach for these indications.

Key Clinical Topics

• Liver transplantation for hepatocellular carcinoma (HCC) as a reference standard
• Perihilar cholangiocarcinoma and the Mayo Protocol
• Intrahepatic cholangiocarcinoma transplant indications
• Colorectal liver metastases and transplant eligibility
• Living donor liver transplantation (LDLT) as the optimal strategy for oncologic indications
• Role of immunotherapy in pre- and post-transplant phases
• OPTN/UNOS policy changes and MELD exception scores

Key Learning Points

• Transplant oncology: an evolving field combining transplantation and oncology principles, offering potential cure in carefully selected patients based on tumor chronology, biology, and morphology
• MELD exception scoring: recent OPTN policy changes allow exception scores for non-HCC oncologic indications — perihilar cholangiocarcinoma receives median MELD minus 3, intrahepatic cholangiocarcinoma/mixed HCC receives median MELD minus 3, and colorectal metastases receive median MELD minus 20 with a minimum floor of MELD 15
• Living donor liver transplantation: bypasses MELD allocation constraints, allows transplantation at the optimal oncologic window prior to distant metastasis, and offers scheduling flexibility — particularly important for patients with low MELD scores who cannot compete for deceased donor organs
• Milan criteria: transplantation within Milan criteria yields the highest survival and lowest recurrence rates for HCC; downstaging and outside-Milan transplants carry progressively worse outcomes
• RETREAT score: predicts HCC recurrence post-transplant using AFP at transplant, microvascular invasion, largest tumor size, and viable tumor count at explant; score >5 indicates significantly increased recurrence risk
• Immunotherapy and transplantation: checkpoint inhibitors can bridge patients to transplant but carry risk of acute rejection and liver failure in ~50% of cases; optimal washout period is approximately 3–6 months before transplantation
• Perihilar cholangiocarcinoma diagnosis: requires positive biliary cytology/biopsy or combination of malignant-appearing stricture, elevated CA 19-9, and suspicious cytology; AASLD recommends transplantation for tumors <3 cm without intrahepatic or extrahepatic metastases
• Mayo Protocol: neoadjuvant chemoradiation with external beam radiation and 5-FU, followed by brachytherapy and maintenance capecitabine, then staging laparotomy prior to transplantation; pre-transplant tumor biopsy is contraindicated due to seeding risk
• Contraindications for perihilar cholangiocarcinoma transplant: lymph node metastases are an absolute contraindication; tumor plane violation excludes candidacy
• Patient selection framework: combines tumor chronology (duration and response to treatment), tumor biology (aggressiveness), and morphology

Clinical Data & Study Results

• Mayo Protocol original series (2005): 1-, 3-, and 5-year survival rates of 92%, 82%, and 82% for unresectable early-stage perihilar cholangiocarcinoma
• Multi-center perihilar cholangiocarcinoma study: recurrence-free survival of 78%, 65%, and 59% at 1, 5, and 10 years in patients with CA 19-9 >100 µg/mL who completed neoadjuvant therapy
• TRANSFER trial (preliminary): compared neoadjuvant radiochemotherapy plus transplantation versus resection in 20 patients per arm; intention-to-treat analysis showed no transplant benefit due to a >50% dropout rate before transplantation; outcomes among those transplanted were favorable
• Toronto group/Pittsburgh cohort (n=837): LDLT associated with higher 3-year survival and shorter