Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy
Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy
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DOI：
10.1016/j.ejca.2014.04.001
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发表时间：
2014-07-01
影响因子：
8.4
通讯作者：
Dome, Balazs
中科院分区：
文献类型：
--
作者：
Cserepes, Mihaly;Ostoros, Gyula;Dome, Balazs
背景：以铂为基础的化疗是晚期肺腺癌最常见的治疗方法。由于KRAS突变状态在这一背景下的临床意义尚未明确，我们对接受铂类化疗的高加索突变晚期肺腺癌患者中迄今为止最大的一组KRAS突变亚型特异性突变进行了分析。方法：505例已知氨基酸替代特异性KRAS突变状态的高加索人晚期肺腺癌患者接受铂类化疗。结果：338例KRAS野生型患者、147例密码子12突变患者和20例密码子13突变患者的PFS和OS差异无统计学意义(P值分别为0.534和0.917)。东部合作肿瘤组(ECOG)状况和临床分期是影响预后的重要独立因素。KRAS基因突变与吸烟状态显著相关(P=0.018)。然而，重要的是，在从不吸烟者中，G12VKRAS突变患者的发生率显著高于所有其他12KRAS突变(G12x)亚型(P=0.016)。此外，这一亚组有较高的应答率(66%对47%；P=0.077)。G12V突变组的中位PFS也略长(233d；G12x组为175d；P=0.145)。结论：虽然KRAS突变状态本身既不能预测III-IV期肺腺癌的预后，也不能预测其预后，但亚型特异性分析确实可以确定临床上相关的患者亚组，可能最终影响治疗决定。(C)2014年提交人。由爱思唯尔有限公司出版。这是CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/3.0/).下的一篇开放获取文章
Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy.Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed.Results: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145).Conclusions: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).