Volume 122, Issue 5 pp. 955-963
RESEARCH ARTICLE

Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: A novel tumor-burden based prediction model

Diamantis I. Tsilimigras MD

Diamantis I. Tsilimigras MD

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio

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Rittal Mehta MPH

Rittal Mehta MPH

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio

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Alfredo Guglielmi MD

Alfredo Guglielmi MD

Department of Surgery, University of Verona, Verona, Italy

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Francesca Ratti MD

Francesca Ratti MD

Department of Surgery, Ospedale San Raffaele, Milano, Italy

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Hugo P. Marques MD

Hugo P. Marques MD

Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

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Olivier Soubrane MD

Olivier Soubrane MD

Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France

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Vincent Lam MD

Vincent Lam MD

Department of Surgery, Westmead Hospital, Sydney, Australia

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George A. Poultsides MD

George A. Poultsides MD

Department of Surgery, Stanford University, Stanford, California

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Irinel Popescu MD

Irinel Popescu MD

Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania

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Sorin Alexandrescu MD

Sorin Alexandrescu MD

Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania

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Guillaume Martel MD

Guillaume Martel MD

Department of Surgery, University of Ottawa, Ottawa, Canada

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Tom Hugh MD

Tom Hugh MD

Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia

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Luca Aldrighetti MD

Luca Aldrighetti MD

Department of Surgery, Ospedale San Raffaele, Milano, Italy

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Itaru Endo MD, PhD

Itaru Endo MD, PhD

Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan

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Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon)

Corresponding Author

Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon)

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio

Correspondence Timothy M. Pawlik, MD, MPH, PhD, FACS, FRACS (Hon), Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, 395 W, 12th Ave, Suite 670, 43210.

Email: [email protected]

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First published: 29 June 2020
Citations: 21

Abstract

Background

Accurate prediction of recurrence patterns of hepatocellular carcinoma (HCC) may allow for prioritization of patients for resection or transplantation as well as guide post-resection surveillance strategies.

Methods

Patients who underwent curative-intent R0 resection for HCC between 2000 and 2017 were identified using a multi-institutional database. A prognostic model that incorporated HCC tumor burden score (TBS) to predict recurrence beyond the Milan criteria (MC) was developed and validated.

Results

Among 718 patients who underwent R0 resection for HCC, 185 (25.8%) recurred within and 110 (15.3%) beyond the MC. On multivariable analysis, AFP more than 400 ng/mL (hazard ratio [HR] = 2.26; 95% confidence interval [CI]: 1.27-4.02), lymphovascular invasion (HR = 2.00; 95% CI: 1.14-3.50), and TBS (HR = 1.08; 95% CI: 1.03-1.12) were associated with recurrence beyond the MC. A weighted TBS-based score was constructed: [0.074*TBS + 0.692*lymphovascular invasion (yes: 1, no: 0) + 0.816*AFP > 400 (yes:1, no:0)]. Patients with a low, medium, and high TBS-based risk score had a 5-year incidence of recurring beyond the MC of 16.2%, 28.6%, and 47.2%, respectively (P < .001). The predictive accuracy of the model was very good in the training (C-index: 0.761) and validation (C-index: 0.706) datasets and outperformed the previously reported clinical risk score (CRS; C-index: 0.680).

Conclusion

A TBS-based model accurately predicted recurrence beyond MC after curative-intent resection of HCC and outperformed the CRS. Incorporating TBS allows for better risk stratification and identifies patients in need of closer surveillance.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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