Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12967-020-02437-2
Keywords
Intrahepatic cholangiocarcinoma; Next-generation sequencing; Molecular profiling; Target therapy; Immune therapy
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Funding
- Wu Jieping Medical Foundation [320.2710.1857]
- National Natural Science Foundation of China [81874182, 81874056]
- National Key Project of China [2017ZX10203204-007-004]
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Background 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' samples underwent next-generation sequencing (NGS), which analyzed 417 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.
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