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Published on: May 8, 2018
Applied precision cancer medicine in metastatic biliary tract cancer
H Taghizadeh1,2, L Müllauer3, R Mader1,2
1Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Introduction:
Advanced therapy-refractory biliary tract cancer (BTC) has poor prognosis and constitutes a major challenge for adequate treatment strategies. By mapping the molecular profiles of advanced BTC patients, precision cancer medicine may provide targeted therapies for these patients.
Objective:
In this analysis, we aimed to show the potential of PCM in metastatic BTC.
Methods:
In this single-center, real-world retrospective analysis of our PCM platform, we describe the molecular profiling of 30 patients diagnosed with different types of metastatic BTC. Tumor samples of the patients were examined using a 161-gene next-generation sequencing panel, immunohistochemistry (IHC), and fluorescence in situ hybridization for chromosomal translocations.
Results:
In total, we identified 35 molecular aberrations in 30 patients. The predominant mutations were KRAS (n = 8), TP53 (n = 7), IDH2 (n = 4), and IDH1 (n = 3) that accounted for the majority of all molecular alterations (62.86%). BRAF mutations were observed in two patients. Less frequent alterations were noted in ARID1A, CTNNB1, ESR1, FBXW7, FGFR2, MET, NOTCH2, PIK3CA, PTCH1, SMAD4, and SRC1, each in one case. FGFR fusion gene was detected in one patient. No mutations were detected in eight patients. IHC revealed EGFR and p-mTOR expression in 28 patients. Applying these results to our patients, targeted therapy was recommended for 60% of the patients (n = 18). One patient achieved stable disease.
Conclusions:
PCM is a feasible treatment approach and may provide molecular-guided therapy recommendations for metastatic BTC.
Insights
Precision cancer medicine (PCM) shows promise for advanced biliary tract cancer (BTC). Molecular profiling identified actionable targets in 60% of patients, guiding personalized therapy recommendations for this challenging disease.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Advanced, therapy-refractory biliary tract cancer (BTC) presents a significant clinical challenge with a poor prognosis.
- Precision cancer medicine (PCM) offers a potential strategy by identifying molecular profiles to guide targeted therapies in BTC.
Purpose of the Study:
- To evaluate the potential of precision cancer medicine (PCM) in patients with metastatic biliary tract cancer (BTC).
- To demonstrate the feasibility of molecular profiling for guiding treatment decisions in advanced BTC.
Main Methods:
- A retrospective analysis of 30 metastatic BTC patients using a PCM platform.
- Molecular profiling included a 161-gene next-generation sequencing panel, immunohistochemistry (IHC), and fluorescence in situ hybridization.
- Analysis focused on identifying actionable molecular aberrations and targetable alterations.
Main Results:
- Thirty-five molecular aberrations were identified across 30 patients, with KRAS, TP53, IDH2, and IDH1 mutations being predominant.
- Actionable mutations or fusions were detected in a significant proportion of patients, including BRAF mutations and an FGFR fusion gene.
- Immunohistochemistry revealed EGFR and p-mTOR expression in 28 patients, and targeted therapy was recommended for 60% (18/30) of patients.
Conclusions:
- Precision cancer medicine (PCM) is a feasible approach for patients with metastatic biliary tract cancer (BTC).
- Molecular profiling can provide valuable data for recommending targeted therapies, potentially improving treatment strategies for advanced BTC.
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