Precision oncology for intrahepatic cholangiocarcinoma in clinical practice
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Published:2022-08-19
Issue:9
Volume:127
Page:1701-1708
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ISSN:0007-0920
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Container-title:British Journal of Cancer
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language:en
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Short-container-title:Br J Cancer
Author:
Tomczak Aurelie, Springfeld Christoph, Dill Michael T., Chang De-Hua, Kazdal DanielORCID, Wagner Ursula, Mehrabi Arianeb, Brockschmidt Antje, Luedde TomORCID, Naumann Patrick, Stenzinger Albrecht, Schirmacher Peter, Longerich ThomasORCID
Abstract
Abstract
Background
Advanced cholangiocarcinoma has a poor prognosis. Molecular targeted approaches have been proposed for patients after progression under first-line chemotherapy treatment. Here, molecular profiling of intrahepatic cholangiocarcinoma in combination with a comprehensive umbrella concept was applied in a real-world setting.
Methods
In total, 101 patients received molecular profiling and matched treatment based on interdisciplinary tumour board decisions in a tertiary care setting. Parallel DNA and RNA sequencing of formalin-fixed paraffin-embedded tumour tissue was performed using large panels.
Results
Genetic alterations were detected in 77% of patients and included gene fusions in 21 patients. The latter recurrently involved the FGFR2 and the NRG1 gene loci. The most commonly altered genes were BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4 and FGFR3. Molecular targets were detected in 59% of patients. Of these, 32% received targeted therapy. The most relevant reason for not initiating therapy was the deterioration of performance status. Patients receiving a molecular-matched therapy showed a significantly higher survival probability compared to patients receiving conventional chemotherapy only (HR: 2.059, 95% CI: 0.9817–4.320, P < 0.01).
Conclusions
Molecular profiling can be successfully translated into clinical treatment of intrahepatic cholangiocarcinoma patients and is associated with prolonged survival of patients receiving a molecular-matched treatment.
Funder
Bundesministerium für Bildung und Forschung
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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