Objective: Liver transplantation (LT) combined with neoadjuvant chemoradiation (NCR) in well-selected patients with unresectable cholangiocarcinoma (CCA) achieves excellent long-term recurrence-free survival. Current criteria for NCR-LT remain restricted to small and early-stage hilar tumors, excluding patients with locally-advanced CCA from potential cure. This study analyzed outcomes after NCR-LT in locally-advanced CCA to identify factors that predict mortality.

Methods: We analyzed all 24 patients referred to our transplant center for unresectable CCA from January 2013 to August 2017. Inclusion criteria for our NCR-LT treatment protocol were unresectable CCA size ≤8 cm for intrahepatic and ≤3.5 cm for hilar, disease confined to the operative field for total hepatectomy and regional lymphadenectomy during LT, and absence of distant metastasis. 18 patients met our protocol criteria for NCR-LT. Median follow-up was 15 months.

Results: 15 of the 18 patients who initiated NCR presented with tumor burden beyond the Mayo criteria: intrahepatic CCA (n=3), intrahepatic tumor size ≥5 cm or hilar ≥3 cm (n=6), PET-positive lymph nodes (n=8), and prior resection (n=3) and chemotherapy (n=2). 5 patients were successfully downstaged and received LT (median wait time 13.2 months); 3 await LT; and 10 were removed from the waitlist due to tumor progression while on NCR (n=6), or uncontrolled infection and failure to thrive (n=4).

On multivariable analysis, hilar tumor and large size predicted dropout while on NCR (95% credible interval 0.58-0.99). Median NCR duration was significantly shorter for patients who progressed than those who survived to LT (4.9 vs 13.3 months, p=0.048). Of the 5 LT patients, 3 are alive with no recurrence (8.6-19.9 months post-LT), 1 died of non-tumor-related cause, and 1 recurred at 12 months. Patients who did not receive LT died at a median of 11.8 months after diagnosis.

Conclusion: NCR-LT for locally-advanced CCA achieved acceptable short-term disease-free survival. Our study shows that patients with unfavorable tumor biology progressed early despite NCR. As such, those with favorable tumor response to NCR would benefit from a shorter wait time for an expedited LT.

CITATION INFORMATION: Wong M., Kim J., Eriksen C., Pearson T., Robbins J., George B., Zimmerman M., Hong J. Outcomes Analysis of Liver Transplantation Combined with Neoadjuvant Therapy in Patients with Unresectable Locally-Advanced Cholangiocarcinoma Am J Transplant. 2017;17 (suppl 3).

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