Liver Surgery Department, Shanghai Cancer Center, Fudan University, No. 270 Dongan Rd., Shanghai, 200032, People's Republic of China.
Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China.
J Transl Med. 2020 Jul 6;18(1):273. doi: 10.1186/s12967-020-02437-2.
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.
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.
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.
This study provides an overview of genetic alterations in Chinese ICC patients and indicates the potential clinical implications for NGS-based personalized therapies.
中国人群内的肝内胆管癌（ICC）的基因组改变尚未完全揭示。分子谱分析可为临床管理，特别是靶向治疗提供参考。
对 122 例 ICC 患者进行回顾性研究。所有患者的样本均进行了下一代测序（NGS），分析了 417 个基因。分析了遗传特征、临床管理和治疗反应。
最常见的突变基因是 TP53（34%）、KRAS（25%）和 ARID1A（17%）。根据分子谱分析，结合化疗，使用靶向药物。22 例 KRAS/NRAS/BRAF 野生型患者接受西妥昔单抗治疗。疾病控制率和反应率分别为 78%和 47%，高于单纯化疗（72%和 11%，P=0.16）。54 例患者接受贝伐单抗抗 VEGF 治疗。疾病控制率和反应率分别为 85%和 60%。与单纯化疗组相比，贝伐单抗组的治疗效果（P=0.001）和无进展生存期（PFS）更长（15.4 个月和 6.7 个月，P=0.04）。联合化疗和贝伐单抗治疗后行肝切除术的 10 例患者的 PFS 长于单纯手术治疗的 139 例患者（28.9 个月和 18.0 个月，P=0.03）。2 例（1.6%）患者存在微卫星不稳定（MSI-H）特征，均受益于免疫治疗。
本研究概述了中国 ICC 患者的遗传改变，并表明基于 NGS 的个性化治疗具有潜在的临床意义。
Zotero 插件
