International Validation and Refinement of Oncological Borderline Resectability Criteria for Hepatocellular Carcinoma Using Tumor Burden Score to Predict Survival

Miho Akabane, MD; Jun Kawashima, MD; Abdullah Altaf, MD; Selamawit Woldesenbet, PhD; François Cauchy, MD; Federico Aucejo, MD; Irinel Popescu, MD, PhD; Minoru Kitago, MD, PhD; Guillaume Martel, MD; Francesca Ratti, MD; Luca Aldrighetti, MD; George A. Poultsides, MD; Yuki Imaoka, MD, PhD; Andrea Ruzzenente, MD, PhD; Itaru Endo, MD, PhD; Ana Gleisner, MD, PhD; Hugo P. Marques, MD; Sara Oliveira, MD; Jorge Balaia, MD; Vincent Lam, MD; Tom Hugh, MD; Nazim Bhimani, PhD; Feng Shen, MD; Timothy M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS, FSSO, FRACS (Hon.)

doi:10.1097/as9.0000000000000557

Annals of Surgery Open (Mar 2025)

International Validation and Refinement of Oncological Borderline Resectability Criteria for Hepatocellular Carcinoma Using Tumor Burden Score to Predict Survival

Miho Akabane, MD,
Jun Kawashima, MD,
Abdullah Altaf, MD,
Selamawit Woldesenbet, PhD,
François Cauchy, MD,
Federico Aucejo, MD,
Irinel Popescu, MD, PhD,
Minoru Kitago, MD, PhD,
Guillaume Martel, MD,
Francesca Ratti, MD,
Luca Aldrighetti, MD,
George A. Poultsides, MD,
Yuki Imaoka, MD, PhD,
Andrea Ruzzenente, MD, PhD,
Itaru Endo, MD, PhD,
Ana Gleisner, MD, PhD,
Hugo P. Marques, MD,
Sara Oliveira, MD,
Jorge Balaia, MD,
Vincent Lam, MD,
Tom Hugh, MD,
Nazim Bhimani, PhD,
Feng Shen, MD,
Timothy M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS, FSSO, FRACS (Hon.)

Affiliations

Miho Akabane, MD: From the * Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
Jun Kawashima, MD: From the * Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
Abdullah Altaf, MD: From the * Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
Selamawit Woldesenbet, PhD: From the * Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
François Cauchy, MD: † Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
Federico Aucejo, MD: ‡ Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
Irinel Popescu, MD, PhD: § Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
Minoru Kitago, MD, PhD: ‖ Department of Surgery, Keio University, Tokyo, Japan
Guillaume Martel, MD: ¶ Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Francesca Ratti, MD: # Department of Surgery, Ospedale San Raffaele, Milan, Italy
Luca Aldrighetti, MD: # Department of Surgery, Ospedale San Raffaele, Milan, Italy
George A. Poultsides, MD: ** Department of Surgery, Stanford University, Stanford, CA
Yuki Imaoka, MD, PhD: ** Department of Surgery, Stanford University, Stanford, CA
Andrea Ruzzenente, MD, PhD: †† Department of Surgery, University of Verona, Verona, Italy
Itaru Endo, MD, PhD: ‡‡ Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
Ana Gleisner, MD, PhD: §§ Department of Surgery, University of Colorado, Denver, CO
Hugo P. Marques, MD: ‖‖ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
Sara Oliveira, MD: ‖‖ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
Jorge Balaia, MD: ‖‖ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
Vincent Lam, MD: ¶¶ Department of Surgery, Westmead Hospital, Sydney, New South Wales, Australia
Tom Hugh, MD: ## Department of Surgery, School of Medicine, The University of Sydney, Sydney, New South Wales, Australia
Nazim Bhimani, PhD: ## Department of Surgery, School of Medicine, The University of Sydney, Sydney, New South Wales, Australia
Feng Shen, MD: *** Department of Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Timothy M. Pawlik, MD, PhD, MPH, MTS, MBA, FACS, FSSO, FRACS (Hon.): From the * Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH

DOI: https://doi.org/10.1097/as9.0000000000000557
Journal volume & issue: Vol. 6, no. 1
p. e557

Abstract

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Objective:. The aim of this study is to externally validate the original borderline resectability (BR) category for predicting overall survival (OS) in hepatocellular carcinoma (HCC) following resection and to assess whether incorporating the tumor burden score (TBS) and other clinical factors could enhance predictive accuracy. Background:. A recent Japanese expert panel introduced a new HCC classification scheme: resectable (R), borderline resectable 1 (BR1), and borderline resectable 2 (BR2). Methods:. Patients undergoing curative-intent hepatectomy for HCC (2000–2023) were classified as R, BR1, and BR2 using the original BR and a novel TBS-BR category. The TBS-BR category replaces BR’s categorical tumor morphology factors with the continuous TBS (TBS² = [maximum tumor diameter]² + [number of tumors]²). Multivariable analysis identified oncologic, morphometric, and patient-level factors associated with OS, which were incorporated into an online predictive tool. Results:. Among 1766 patients, the original BR category grouped 1504 (85.2%) as R, 249 (14.1%) as BR1, and 13 (0.7%) as BR2. Utilizing the TBS-BR category, patients were reclassified as TBS-BR R (n = 684, 38.7%), BR1 (n = 1009, 57.1%), and BR2 (n = 73, 4.1%). Both the original and TBS-BR categories correlated with 5-year OS (original: 65.1%, 48.2%, 46.4%; TBS-BR: 70.8%, 58.3%, 40.0%; P 2 (HR: 1.40 [1.09–1.80]; P = 0.007), albumin-bilirubin (ALBI) score (HR: 1.51 [1.21–1.88]; P < 0.001), and log α-fetoprotein (AFP) (HR: 1.07 [1.03–1.11]; P < 0.001) were independently associated with OS. A TBS-BR composite model based on these factors (TBS-BR category, ASA class, ALBI score, and log AFP) was developed and made available online (https://makbn.shinyapps.io/BRHCC/). The model’s area under the receiver operating characteristic at 5 years (0.70) outperformed both the original BR (0.57) and Barcelona Clinic Liver Cancer classification (0.64). Conclusions:. The TBS-BR composite model, integrating tumor morphology (TBS), tumor biology (log AFP), overall physical status (ASA class), and liver function (ALBI score) demonstrated superior predictive accuracy for OS compared with the original BR and Barcelona Clinic Liver Cancer classifications.

Published in Annals of Surgery Open

ISSN: 2691-3593 (Online)
Publisher: Wolters Kluwer Health
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: https://journals.lww.com/aosopen/pages/default.aspx

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