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Overall Tumor Burden Dictates Outcomes For Patients Undergoing Resection Of Multinodular Hepatocellular Carcinoma Beyond The Milan Criteria
*Diamantis I. Tsilimigras1, *Rittal Mehta1, *Dimitrios Moris1, *Anghela Z Paredes1, *Kota Sahara1, *James Madison Hyer1, *Fabio Bagante2, *Francesca Ratti3, *Hugo P. Marques4, *Olivier Soubrane5, *Vincent Lam6, *George A. Poultsides7, *Irinel Popescu8, *Sorin Alexandrescu8, *Guillaume Martel9, *Aklile Workneh9, *Alfredo Guglielmi2, *Tom Hugh10, *Luca Aldrighetti3, *Itaru Endo11, Timothy M Pawlik1
1The Ohio State University, Columbus, OH;2University of Verona, Verona, Italy3Ospedale San Raffaele, Milano, Italy4Curry Cabral Hospital, Lisbon, Portugal5Beaujon Hospital, Clichy, France6Westmead Hospital, Sydney, Australia7Stanford University, Palo Alto, CA;8Fundeni Clinical Institute, Bucharest, Romania9University of Ottawa, Ottawa, ON, Canada10The University of Sydney, Sydney, Australia11Yokohama City University School of Medicine, Yokohama, Japan

OBJECTIVE(S): Liver resection for multinodular HCC (MHCC), especially beyond the Milan criteria, remains controversial. We sought to define surgical outcomes following resection of MHCC, as well as develop a prediction tool to identify which patients likely benefit most from resection of MHCC.
METHODS: Patients who underwent curative-intent resection for MHCC beyond Milan criteria between 2001-2017 were identified using a multi-institutional database. Pre-and post-operative overall survival(OS) prediction models that included HCC tumor burden score(TBS) defined as distance from the origin on a Cartesian plane that incorporated maximum tumor size and lesion number were developed and validated.
RESULTS: Among 1,287 patients who underwent resection for HCC, 164(12.7%) had MHCC beyond the Milan criteria. Among patients with MHCC, 31(18.9%) patients experienced a serious complication and 90-day mortality was 3.6%(n=6). 5-year OS following MHCC resection was 53.6%. A preoperative TBS-based model (5-year OS: low-risk,73.8% vs. mid-risk,46.8% vs. high-risk,13.1%), as well as post-operative TBS-based model (5-year OS: low-risk,80.6% vs. mid-risk,38.8% vs. high-risk,16.0%) categorized patients into distinct prognostic groups relative to long-term prognosis (both p<0.001)(Figure). Predictive accuracy of the pre- and postoperative models was very good in the training (c-index;pre:0.68; post:0.70) as well as validation (c-index,pre:0.68; post:0.71) datasets.
CONCLUSIONS: Prognosis of patients with MHCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with MHCC beyond the Milan criteria who have a low-or mid-TBS based risk.



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