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 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.