Precision oncology for intrahepatic cholangiocarcinoma in clinical practice

被引:27
作者
Tomczak, Aurelie [1 ,2 ]
Springfeld, Christoph [2 ,3 ]
Dill, Michael T. [2 ,4 ,5 ]
Chang, De-Hua [2 ,6 ]
Kazdal, Daniel [1 ]
Wagner, Ursula [1 ,2 ,3 ]
Mehrabi, Arianeb [2 ,7 ]
Brockschmidt, Antje [2 ,8 ]
Luedde, Tom [9 ]
Naumann, Patrick [2 ,10 ]
Stenzinger, Albrecht [1 ]
Schirmacher, Peter [1 ,2 ]
Longerich, Thomas [1 ,2 ]
机构
[1] Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany
[2] Liver Canc Ctr Heidelberg, Heidelberg, Germany
[3] Natl Ctr Tumor Dis, Med Oncol, Heidelberg, Germany
[4] Heidelberg Univ Hosp, Dept Gastroenterol, Intoxicat, Infect Dis, Heidelberg, Germany
[5] German Canc Res Ctr, Expt Hepatol Inflammat & Canc Res Grp, Heidelberg, Germany
[6] Heidelberg Univ Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany
[7] Heidelberg Univ Hosp, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany
[8] Natl Ctr Tumor Dis, Clin Canc Registry, Heidelberg, Germany
[9] Univ Hosp Dusseldorf, Clin Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany
[10] Heidelberg Univ Hosp, Dept Radiat Oncol, Heidelberg, Germany
关键词
BILIARY-TRACT CANCER; OPEN-LABEL; METASTATIC CHOLANGIOCARCINOMA; SINGLE-ARM; MULTICENTER; CHEMOTHERAPY; METAANALYSIS; MEDICINE; GENOMICS;
D O I
10.1038/s41416-022-01932-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1701 / 1708
页数:8
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