Journal of the American College of Surgeons · 2024
Exploring the Clinical Use of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic.
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Purchla Julia, Ghabi Elie M, Burns William R, Lafaro Kelly J, Burkhart Richard A, Cameron John L, Yarchoan Mark, Shubert Christopher R, Baretti Marina, He Jin
Аннотация
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.
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.