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Exploring the Clinical Use of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive
Julia Purchla1, Elie M Ghabi1, William R Burns1
1From the Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD (Purchla, Ghabi, Burns, Lafaro, Burkhart, Cameron, Shubert, He).
Background:
Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic.
Study Design:
Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded.
Results:
Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02).
Conclusions:
Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.
Insights
Molecular profiling frequently detects actionable alterations in intrahepatic cholangiocarcinoma (ICC). Identifying these molecular targets is linked to improved overall survival (OS) for ICC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Intrahepatic cholangiocarcinoma (ICC) molecular profiling aids in identifying actionable molecular alterations.
- These alterations can guide the selection of targeted therapies for ICC patients.
- This study examines the clinical utility of molecular profiling within a multidisciplinary ICC clinic.
Purpose of the Study:
- To investigate the clinical application and impact of molecular profiling in intrahepatic cholangiocarcinoma (ICC).
- To determine the frequency of actionable molecular alterations in ICC patients.
- To assess the association between detected alterations and overall survival (OS).
Main Methods:
- Retrospective review of 194 patients with ICC diagnosed between 2019-2023.
- Analysis of molecular profiles and targeted therapy use.
- Correlation of actionable molecular alterations with overall survival (OS), excluding patients with OS < 2 months.
Main Results:
- Molecular profiling was performed on 125 (64%) of 194 ICC patients.
- Actionable molecular alterations were found in 56 (45%) profiled patients, including various genetic mutations and fusions.
- Detection of actionable alterations was associated with improved mean OS (34.1 vs 23.6 months, p=0.008) in 120 patients.
Conclusions:
- Actionable molecular alterations are common in intrahepatic cholangiocarcinoma (ICC).
- Identifying these alterations is associated with enhanced overall survival (OS).
- Further prospective studies are needed to explore the role of targeted therapies in ICC management.
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