Neoadjuvant Therapy Regimens for Hilar Cholangiocarcinoma Before Liver Transplant

Abstract

Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation. Neoadjuvant protocols often include radiotherapy (RT), however there is no standard approach. The purpose of this study is to characterize practice patterns of RT use prior to transplantation for hilar cholangiocarcinoma.A survey was administered to radiation oncologists practicing at liver transplantation centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey was distributed via SurveyMonkey and consisted of 13 questions regarding RT details including technique, brachytherapy use, target volumes, dose/fractionation, as well as approaches to systemic therapy. The cumulative tumor dose was standardized using the EQD2 method for cross comparison of regimens RESULTS: Twenty-three unique centers utilizing neoadjuvant therapy for hCCA were identified from an initial cohort of 124 radiation oncologists contacted. Most respondents (96%) integrate both systemic and RT as part of their protocol. SBRT to the primary alone without elective nodal coverage was utilized in 3 (13%) centers while most did include elective nodal regions in the RT fields. Elective nodal volumes commonly included the portal lymph nodes (91%), celiac artery lymph nodes (70%), and hepatic artery lymph nodes (61%). In total, 18 centers report using a boost with total EQD2 outlined in Table 1. Two centers used integrated boosts to 60 or 54 Gy in 25 fractions (fx). After an initial 45 Gy plan, a wide range of sequential boost regimens are used including 9 Gy (1.5 Gy BID n = 3, 1.8 Gy daily n = 2), 20 Gy (4-5 fx N = 3), 15Gy (10 fx n = 1), 16 Gy (4 fx n = 1), 30 Gy (1.5 Gy BID n = 1). The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a range of 40 -110 Gy. Concurrent chemotherapy with a fluoropyrimidine was utilized in most (96%). Chemotherapy after the RT was most common (78%), including Capecitabine in 10(43%) and Gemcitabine/Cisplatin in 6(26%) centers. Neoadjuvant chemotherapy was used in two centers (9%).These results suggest significant variability of neoadjuvant RT use for unresectable hilar cholangiocarcinoma prior to transplant. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 -110 Gy (EQD2). Further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.