Impact of Molecular Alterations on Survival in Biliary Tract Cancers: A Retrospective Belgian Cohort Study
6 affiliations
- 1Department of Pathology Antwerp University Hospital Edegem Belgium
- 2Department of Oncology Antwerp University Hospital Edegem Belgium
- 3Center for Oncological Research (CORE), University of Antwerp Wilrijk Belgium
- 4Department of Pathology University of Maastricht, Maastricht University Medical Center Maastricht the Netherlands
- 5Department of Hepatobiliary, Transplant and Endocrine Surgery Antwerp University Hospital Edegem Belgium
- 6Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), University of Antwerp Wilrijk Belgium
Abstract
Biliary tract cancers (BTCs) are aggressive malignancies associated with a poor prognosis. Although molecular profiling is recommended to guide therapeutic decision‐making, real‐practice data on the prevalence and prognostic significance of genomic alterations in European BTC cohorts remain limited. This retrospective cohort study characterized the molecular landscape of BTCs in a Belgian real‐practice setting and evaluated its prognostic relevance. Patients with BTC who underwent informative molecular testing as part of routine diagnostics at Antwerp University Hospital between 2016 and 2024 were included. Demographic, clinical, and molecular data were extracted from electronic health records. Survival outcomes were analyzed using Kaplan–Meier methods and Cox proportional hazards regression. Among 224 included patients, genomic alterations were identified in 59.4% of tumors, with clear subtype‐specific patterns. IDH1 mutations (17.3%) and FGFR2 fusions (13.9%) were exclusively observed in intrahepatic cholangiocarcinoma, KRAS mutations were most prevalent in extrahepatic cholangiocarcinoma (42.9%), and ERBB2 amplification was enriched in gallbladder cancer (16.7%). Co‐occurring alterations were present in 7.8% of cases. KRAS mutation was the most frequent alteration overall (20.4%) and remained significantly associated with worse overall survival in multivariate analysis adjusted for tumor subtype and tumor stage (HR = 1.54, 95% CI: 1.03–2.31, p = 0.04). Although 32.6% of tumors harbored a potentially actionable alteration, only 31.6% of eligible patients received matched targeted therapy. These findings underscore the clinical value of routine molecular profiling in BTC and highlight its importance for identifying therapeutic opportunities in clinical practice.
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BibTeX
@article{arnouts2026impact,
title = {{Impact of Molecular Alterations on Survival in Biliary Tract Cancers: A Retrospective Belgian Cohort Study}},
author = {Jorine Arnouts and Léon C. van Kempen and Senada Koljenović and Helena Oliveres and Pieterjan Vanclooster and Hans Prenen and Caro De Weerdt and Siddharth Chhajlani and Geert Roeyen and Laure Sorber and Koen De Winne and Jonas Dahnoun and Greetje Vanhoutte and Timon Vandamme and Karen Zwaenepoel},
journal = {International Journal of Cancer},
year = {2026},
month = aug,
doi = {10.1002/ijc.70711},
url = {https://doi.org/10.1002/ijc.70711},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Impact of Molecular Alterations on Survival in Biliary Tract Cancers: A Retrospective Belgian Cohort Study
AU - Jorine Arnouts
AU - Léon C. van Kempen
AU - Senada Koljenović
AU - Helena Oliveres
AU - Pieterjan Vanclooster
AU - Hans Prenen
AU - Caro De Weerdt
AU - Siddharth Chhajlani
AU - Geert Roeyen
AU - Laure Sorber
AU - Koen De Winne
AU - Jonas Dahnoun
AU - Greetje Vanhoutte
AU - Timon Vandamme
AU - Karen Zwaenepoel
PY - 2026
DA - 2026/08/21
JO - International Journal of Cancer
DO - 10.1002/ijc.70711
UR - https://doi.org/10.1002/ijc.70711
AB - Biliary tract cancers (BTCs) are aggressive malignancies associated with a poor prognosis. Although molecular profiling is recommended to guide therapeutic decision‐making, real‐practice data on the prevalence and prognostic significance of genomic alterations in European BTC cohorts remain limited. This retrospective cohort study characterized the molecular landscape of BTCs in a Belgian real‐practice setting and evaluated its prognostic relevance. Patients with BTC who underwent informative molecular testing as part of routine diagnostics at Antwerp University Hospital between 2016 and 2024 were included. Demographic, clinical, and molecular data were extracted from electronic health records. Survival outcomes were analyzed using Kaplan–Meier methods and Cox proportional hazards regression. Among 224 included patients, genomic alterations were identified in 59.4% of tumors, with clear subtype‐specific patterns. IDH1 mutations (17.3%) and FGFR2 fusions (13.9%) were exclusively observed in intrahepatic cholangiocarcinoma, KRAS mutations were most prevalent in extrahepatic cholangiocarcinoma (42.9%), and ERBB2 amplification was enriched in gallbladder cancer (16.7%). Co‐occurring alterations were present in 7.8% of cases. KRAS mutation was the most frequent alteration overall (20.4%) and remained significantly associated with worse overall survival in multivariate analysis adjusted for tumor subtype and tumor stage (HR = 1.54, 95% CI: 1.03–2.31, p = 0.04). Although 32.6% of tumors harbored a potentially actionable alteration, only 31.6% of eligible patients received matched targeted therapy. These findings underscore the clinical value of routine molecular profiling in BTC and highlight its importance for identifying therapeutic opportunities in clinical practice.
SN - 0020-7136
SN - 1097-0215
ER -