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Complete Pathologic Response to Pretransplant Locoregional Therapy for Hepatocellular Carcinoma Defines Cancer Cure after Liver Transplantation: Analysis of 501 Consecutively Treated Patients
Vatche G. Agopian*, Maud Morshedi*, Michael Harlander-Locke*, Justin McWilliams*, Ali Zarrinpar*, Fady M. Kaldas*, Douglas G. Farmer, Daniela Markovic*, Hasan Yersiz*, Jonathan R. Hiatt, Ronald W Busuttil
UCLA, Los Angeles, CA

OBJECTIVE: Patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) have variable risks of tumor progression, waitlist dropout, and post-transplant recurrence. Pretransplant locoregional therapies (LRT; percutaneous ablations, transarterial embolizations) mitigate these risks by inducing tumor necrosis. We evaluated the rate of complete pathological response (cPR) in patients undergoing LRT, the effect of LRT on post-LT HCC recurrence and survival, and factors associated with cPR.
METHODS: Comparisons were made among HCC recipients with and without cPR who received pre-LT LRT from 1994 to 2013. Multivariate logistic regression identified predictors of achieving cPR.
RESULTS: Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT. Post-LT HCC recurrence developed in 57 of 375 patients (15.2%) without cPR compared to 3 of 126 patients (2.4%) with cPR (P<0.001). Recipients with cPR had significantly superior 1-, 3-, and 5-year disease-specific and recurrence-free survival, and only 1 disease-specific death (Figure). Multivariate predictors accurately identified recipients with cPR (c-statistic 0.75, Table).
CONCLUSIONS: Achieving cPR in HCC patients receiving LRT strongly predicts tumor free survival with a negligible risk of HCC recurrence. We identify important factors predicting cPR, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence.

Multivariate Predictors of cPR after LRT for HCC
Odds Ratio95% CIP-value
Radiologic Assessment prior to LT
- No recurrent/residual tumor1.00refref
- Possible recurrent/residual tumor0.450.26-0.780.004
- Definite recurrent/residual tumor0.230.11-0.45<0.001
Post LRT AFP prior to LT = Max pre-LT AFP0.230.06-0.840.027
Lab MELD, per SD decrease1.351.04-1.750.024
Radiological max tumor diameter, per log SD decrease1.250.98-1.590.074
Time from last LRT to LT (days), per SD increase1.241.11-1.39<0.001

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