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Prediction of Recurrence Beyond Milan Criteria After Resection of Hepatocellular Carcinoma- An International Validation of a Clinical Risk Score
Jian Zheng1, Joanne Chou1, Mithat Gonen1, Neeta Vachharajani2, William C. Chapman2, Maria B. Majella Doyle*2, Simon Turcotte*3, Franck Vandenbroucke-Menu*3, Réal Lapointe3, Stefan Buettner4, Bas Groot Koerkamp*4, Chung Yip Chan*5, Brian KP Goh*5, Jin Yao Teo*5, Juinn Huar Kam*5, Jeyaraj P. Raj*5, Peng Chung Cheow*5, Alexander YF Chung*5, Pierce KH Chow6, London LPJ Ooi*5, Vinod P. Balachandran*1, T Peter Kingham1, Peter J. Allen1, Michael I. D'Angelica1, Ronald P. DeMatteo1, William R. Jarnagin1, Ser Yee Lee*5
1Memorial Sloan Kettering Cancer Center, New York, NY;2Washington University School of Medicine, St. Louis, MO;3Université de Montréal, Montreal, QC, Canada4Erasmus Medical Center, Rotterdam, Netherlands5Singapore General Hospital, Singapore, Singapore6Singapore General Hospital and National Cancer Center, Singapore, Singapore

Objective: Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations. This study aims to validate previously reported recurrence clinical risk score (CRS).
Methods: Patients submitted to R0 resection of HCC from 5 international centers were categorized by MC status at presentation and recurrence. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidence was estimated using competing risks methods.
Results: From 1992-2015, 1023 patients were included, of whom 613 (60%) recurred at median follow-up of 50 months. Recurrence beyond MC (n=336, 55%) was more common when initial disease was beyond MC (n=213, 63%) vs. within MC (n=123, 37%). CRS variables were all independent predictors of recurrence beyond MC (HR 1.5-2.1, all p<0.001) and effectively stratified recurrence risk beyond MC, ranging from 19% (CRS=0) to 67% (CRS=3) at 5 years (Figure). Risk of recurrence beyond MC for all patients was 14% if recurrence-free for 2 years and 7% if recurrence-free for 5 years; this risk was 18% and 2%, respectively, with initial disease beyond MC and 11% and 6%, respectively, with initial disease within MC.
Conclusions: HCC recurrence risk beyond MC correlated with initial disease extent but was more accurately predicted by CRS, and while risk decreased over time, never reached zero.

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