Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Liver Cancer Centre Heidelberg, Heidelberg, Germany.
Br J Cancer. 2022 Nov;127(9):1701-1708. doi: 10.1038/s41416-022-01932-1. Epub 2022 Aug 19.
Advanced cholangiocarcinoma has a poor prognosis. Molecular targeted approaches have been proposed for patients after progression under first-line chemotherapy treatment. Here, molecular profiling of intrahepatic cholangiocarcinoma in combination with a comprehensive umbrella concept was applied in a real-world setting.
In total, 101 patients received molecular profiling and matched treatment based on interdisciplinary tumour board decisions in a tertiary care setting. Parallel DNA and RNA sequencing of formalin-fixed paraffin-embedded tumour tissue was performed using large panels.
Genetic alterations were detected in 77% of patients and included gene fusions in 21 patients. The latter recurrently involved the FGFR2 and the NRG1 gene loci. The most commonly altered genes were BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4 and FGFR3. Molecular targets were detected in 59% of patients. Of these, 32% received targeted therapy. The most relevant reason for not initiating therapy was the deterioration of performance status. Patients receiving a molecular-matched therapy showed a significantly higher survival probability compared to patients receiving conventional chemotherapy only (HR: 2.059, 95% CI: 0.9817-4.320, P < 0.01).
Molecular profiling can be successfully translated into clinical treatment of intrahepatic cholangiocarcinoma patients and is associated with prolonged survival of patients receiving a molecular-matched treatment.
晚期胆管癌预后较差。对于一线化疗后进展的患者，已经提出了分子靶向治疗方法。在此，在真实环境中应用了肝内胆管癌的分子谱分析与综合伞式概念相结合的方法。
在三级护理环境中，共有 101 名患者接受了分子谱分析，并根据跨学科肿瘤委员会的决定进行了匹配治疗。使用大型面板平行对福尔马林固定石蜡包埋的肿瘤组织进行了 DNA 和 RNA 测序。
在 77%的患者中检测到了遗传改变，其中包括 21 例基因融合。后者反复涉及 FGFR2 和 NRG1 基因座。最常改变的基因是 BAP1、ARID1A、FGFR2、IDH1、CDKN2A、CDKN2B、PIK3CA、TP53、ATM、IDH2、BRAF、SMARCA4 和 FGFR3。在 59%的患者中检测到了分子靶点。其中，32%的患者接受了靶向治疗。未启动治疗的最相关原因是体能状态恶化。接受分子匹配治疗的患者的生存概率明显高于仅接受常规化疗的患者（HR：2.059，95%CI：0.9817-4.320，P<0.01）。
分子谱分析可以成功转化为肝内胆管癌患者的临床治疗，并与接受分子匹配治疗的患者的生存延长相关。
