Patterns of Recurrence and Progression for Unresectable Cholangiocarcinoma on Orthotopic Liver Transplant Protocol

Abstract

<h3>Purpose/Objective(s)</h3> Neoadjuvant radiotherapy and chemotherapy (CHT) followed by orthotopic liver transplant (OLT) offers the highest chance of disease-free survival for patients with unresectable cholangiocarcinoma (CCA). The purpose of this study was to evaluate patterns of disease recurrence and progression in patients treated on OLT protocol. <h3>Materials/Methods</h3> Through retrospective chart review, we identified patients treated on institutional OLT protocol for unresectable intrahepatic or hilar CCA at a single academic institution from 2012-2019. Patients received SBRT to a total dose of 40 Gy in 5 fractions, delivered over 7-12 days followed by adjuvant CHT (gemcitabine/cisplatin, fluorouracil [5FU] or a capecitabine based regimen). Per protocol, restaging scans were obtained every 3 months until progression or OLT. <h3>Results</h3> Of 26 patients treated on protocol, nine underwent OLT (34.6%), of which six were male (66.7%), median age 51 (36-66), eight hilar tumors (88.9%), one intrahepatic (11.1%), and median size 2.85 cm (2.2-4.3). All patients were treated to 40 Gy in five fractions with a median PTV of 66.6 cc (30.4-202) and median time of 20.4 weeks (8.7-89.1) on adjuvant CHT. Median time from completion of SBRT to OLT was 61.4 weeks (26.6-97.6). Following OLT, four of nine (44.4%) achieved a pathologic complete response (ypT0) in the explanted liver, of which two patients developed recurrence (one at the porta hepatis, one in the lung). Five of nine OLT patients (55.6%) developed recurrent disease (three local, one local and distant, one distant) with median time to recurrence of 49.9 weeks (35.9-127.7) and median time to death of 124.0 weeks (39.3-200.9). Four patients remain in remission with median follow-up of 166.1 weeks (2.4-370.7). 17/26 patients did not proceed to OLT due to disease progression in 13 (10 local, 3 distant), with a median time to progression after SBRT of 37.0 weeks (3.7-81.4), death following recurrent cholangitis in three, and liver failure in one. Median OS for patients who underwent OLT versus those who did not was 172.2 (135.3-285.0) and 78.4 (26.1-219.6) weeks, respectively. <h3>Conclusion</h3> In this small group of patients with unresectable CCA treated with SBRT, CHT, and OLT, there were encouraging rates of pathologic complete response; however, a subset of patients will still develop disease recurrence. All patients who did not make it to OLT developed progression, illustrating a continued unmet need to improve therapeutic options for CCA.