Cholangiocarcinoma With FGFR Genetic Aberrations: A Unique Clinical Phenotype
Cholangiocarcinoma With FGFR Genetic Aberrations: A Unique Clinical Phenotype
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DOI：
10.1200/po.17.00080
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Javle, Milind
中科院分区：
文献类型：
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作者：
Jain, Apurva;Borad, Mitesh J.;Javle, Milind
目的：FGFR基因畸变发生在10%~ 16%的肝内胆管细胞癌中。CCA与FGFR GAs的自然史，共存的GAs的预后作用，与FGFR靶向抑制剂的结果是unknown.Patients和方法CCA与FGFR GAs的患者被确定使用下一代测序或荧光原位杂交从四个三级癌症中心，并与FGFR野生型同行相比。审查的数据包括人口统计学、治疗、总生存期（OS）和GA数据。结果共检出CCA患者377例，FGFR GAs患者95例。FGFR 2 GA最常见（n = 74，63例融合），见于肝内CCA。在CCA患者中，FGFR GAs更常发生于年轻患者（40岁; 6.7%; P < .001），在早期出现（TNM I/II v III/IV期：分别为35.8% v 22%; P = .001），与无FGFR GAs的患者相比，OS更长（分别为37 v 20个月; P < .001）。在排除36例接受FGFR抑制剂治疗的患者后，这种差异仍然显著。CCA与FGFR 2融合（n = 63）与其他FGFR GA（n = 29）之间的OS无差异（P = 0.60）。与标准治疗相比，FGFR GAs患者接受FGFR靶向治疗的OS更好（P = .01）。BAP 1突变是最常见的共存突变，无预后影响，而TP 53（P = 0.04）和CDKN 2A/B（P = 0.04）与较短的OS相关。结论FGFRGA的CCA代表了病程缓慢的年轻患者中发生的独特亚型。FGFR靶向治疗可能对该亚组的OS产生积极影响。(C)2018年美国临床肿瘤学会
Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown.Patients and Methods Patients with CCA with FGFR GAs were identified using nextgeneration sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher's exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis.Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients ( 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference (P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment (P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 (P = .04) and CDKN2A/B (P = .04) were correlated with a shorter OS.Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup. (C) 2018 by American Society of Clinical Oncology