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

Abstract

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 had results of 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, with a combination of 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; 15.4 vs 6.7 months, P=0.04) were observed in the bevacizumab-treated group than in the chemotherapy alone group. 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.