Comprehensive molecular profiling of intrahepatic cholangiocarcinoma in the Chinese population and therapeutic experience

Autor:	Yun Feng, Xigan He, Longrong Wang, Anrong Mao, Zhenhai Lin, Yi-Lin Wang, Miao Wang, Yiming Zhao, Qi Pan, Weiping Zhu, Ning Zhang, Hongxu Zhu, Jiamin Zhou, Yong Fa Zhang, Weiqi Xu, Lu Wang
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine Oncology China medicine.medical_specialty Bevacizumab medicine.medical_treatment lcsh:Medicine medicine.disease_cause Target therapy General Biochemistry Genetics and Molecular Biology Targeted therapy Cholangiocarcinoma 03 medical and health sciences Molecular profiling 0302 clinical medicine Internal medicine medicine Humans Intrahepatic Cholangiocarcinoma Retrospective Studies Intrahepatic cholangiocarcinoma Chemotherapy Cetuximab business.industry Research lcsh:R Microsatellite instability Retrospective cohort study General Medicine medicine.disease Bile Ducts Intrahepatic 030104 developmental biology Bile Duct Neoplasms Immune therapy 030220 oncology & carcinogenesis Mutation Next-generation sequencing KRAS business medicine.drug
Zdroj:	Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-11 (2020) Journal of Translational Medicine
ISSN:	1479-5876
DOI:	10.1186/s12967-020-02437-2
Popis:	PURPOSE: The genomic alterations of intrahepatic cholangiocarcinoma (ICC) in the Chinese population have not been fully revealed. Molecular profiling may provide a reference for clinical management, especially targeted therapy. METHODS: A retrospective study was conducted in 122 ICC patients. All patients have been performed next-generation sequencing (NGS) assays that analyzed 417 cancer-associated genes. The genetic characteristics, clinical management and therapeutic responses were analyzed. RESULTS: The most commonly mutated genes were TP53 (34%), KRAS (25%) and ARID1A (17%). Targeted agents were used referring to molecular profiling, in combination with chemotherapy. Twenty-two patients with wild-type KRAS/NRAS/BRAF were treated with cetuximab. The disease control and response rates were 78% and 47%, respectively, which were higher than those achieved with chemotherapy alone (72% and 11%, P=0.16). Fifty-four patients underwent anti-VEGF treatment with bevacizumab. The disease control and response rates were 85% and 60%, respectively. Better therapeutic efficiency (P=0.001) and longer progression-free survival (PFS) were observed in the bevacizumab-treated group compared to chemotherapy alone group (15.4 and 6.7 months, respectively; P=0.04) . The PFS of ten patients who underwent hepatectomy after combined treatment with chemotherapy and bevacizumab was longer than that of 139 patients who underwent surgical treatment (28.9 vs 18.0 months, P=0.03). Two patients (1.6%) had signatures of microsatellite instability (MSI-H), and both benefited from immunotherapy. CONCLUSIONS: This study provides an overview of genetic alterations in Chinese ICC patients and indicates the potential clinical implications for NGS-based personalized therapies.
Databáze:	OpenAIRE
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