Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma: The Synergistic Impact of the FIB-4 Index and Tumor Burden Score on Post-hepatectomy Outcomes

Miho Akabane; Jun Kawashima; Selamawit Woldesenbet; Amanda B Macedo; François Cauchy; Feng Shen; Shishir K Maithel; Bas Groot Koerkamp; Sorin Alexandrescu; Minoru Kitago; Matthew Weiss; Guillaume Martel; Carlo Pulitano; Luca Aldrighetti; George A Poultsides; Yuki Imaoka; Alfredo Guglielmi; Todd W Bauer; Itaru Endo; Ana Gleisner; Hugo P Marques; Timothy M Pawlik

doi:10.1245/s10434-024-16455-7

Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma: The Synergistic Impact of the FIB-4 Index and Tumor Burden Score on Post-hepatectomy Outcomes

Ann Surg Oncol. 2025 Feb;32(2):1011-1020. doi: 10.1245/s10434-024-16455-7. Epub 2024 Nov 7.

Authors

Miho Akabane¹, Jun Kawashima¹, Selamawit Woldesenbet¹, Amanda B Macedo¹, François Cauchy², Feng Shen³, Shishir K Maithel⁴, Bas Groot Koerkamp⁵, Sorin Alexandrescu⁶, Minoru Kitago⁷, Matthew Weiss⁸, Guillaume Martel⁹, Carlo Pulitano¹⁰, Luca Aldrighetti¹¹, George A Poultsides¹², Yuki Imaoka¹², Alfredo Guglielmi¹³, Todd W Bauer¹⁴, Itaru Endo¹⁵, Ana Gleisner¹⁶, Hugo P Marques¹⁷, Timothy M Pawlik^{18

19}

Affiliations

¹ Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
² Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France.
³ Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
⁴ Department of Surgery, Emory University, Atlanta, GA, USA.
⁵ Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
⁶ Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania.
⁷ Department of Surgery, Keio University, Tokyo, Japan.
⁸ Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
⁹ Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.
¹⁰ Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia.
¹¹ Department of Surgery, Ospedale San Raffaele, Milan, Italy.
¹² Department of Surgery, Stanford University, Stanford, CA, USA.
¹³ Department of Surgery, University of Verona, Verona, Italy.
¹⁴ Department of Surgery, University of Virginia, Charlottesville, VA, USA.
¹⁵ Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
¹⁶ Department of Surgery, University of Colorado, Denver, CO, USA.
¹⁷ Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal.
¹⁸ Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. [email protected].
¹⁹ Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Oncology, Health Services Management and Policy, Wexner Medical Center, The Ohio State University, Columbus, OH, USA. [email protected].

PMID: 39511008
DOI: 10.1245/s10434-024-16455-7

Abstract

Background: The prognostic role of the fibrosis-4 (FIB-4) index relative to intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study sought to characterize the impact of the FIB-4 index and tumor burden score (TBS) on recurrence and overall survival (OS).

Methods: ICC patients undergoing hepatectomy (2000-2020) were identified using a multi-institutional database. Patients were categorized as low (low TBS/low FIB-4 index), intermediate (low TBS/high FIB-4 index or high TBS/low FIB-4 index), and high (high TBS/high FIB-4 index).

Results: Among 1168 patients in different TBS and FIB-4 index cohorts, 3-year recurrence varied considerably. For instance, among the patients with low TBS, individuals with a high FIB-4 index had a greater risk of recurrence than patients with a low FIB-4 index (59.9 vs. 47.7%; P = 0.01). Among patients with a high TBS, individuals with a high versus a low FIB-4 index had a higher incidence of recurrence (76.8 vs. 69.0%; P = 0.04). A similar pattern was observed among patients with both a low FIB-4 index (low [47.7%] vs. high [69.0%] TBS) and a high FIB-4 index (low [59.9%] vs. high [76.8%] TBS; both P < 0.001). Patients with a high [27.5%] versus a low [48.8%] TBS; P < 0.001) and patients with a high [34.2%] versus a low [43.5%] FIB-4 index; P = 0.01) had a worse OS. The multivariable analysis demonstrated an increasing risk of recurrence in the intermediate-index (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.20-2.16; P = 0.001) and high-index (HR, 2.13; 95% CI 1.45-3.13; P < 0.001) groups versus the low-index group.

Conclusions: Both tumor-related and non-tumorous characteristics should be used to predict risk of recurrence and survival more accurately among patients with ICC following hepatic resection.

Keywords: Fibrosis-4 (FIB-4) index; Hepatectomy; Intrahepatic cholangiocarcinoma (ICC); Overall survival (OS); Recurrence; Tumor Burden Score (TBS).

MeSH terms

Aged
Bile Duct Neoplasms* / pathology
Bile Duct Neoplasms* / surgery
Cholangiocarcinoma* / pathology
Cholangiocarcinoma* / surgery
Female
Follow-Up Studies
Hepatectomy* / mortality
Humans
Male
Middle Aged
Neoplasm Recurrence, Local* / pathology
Prognosis
Retrospective Studies
Survival Rate
Tumor Burden*