Correlation between KRAS mutation status and response to chemotherapy in patients with advanced non-small cell lung cancer☆.
Correlation between KRAS mutation status and response to chemotherapy in patients with advanced non-small cell lung cancer☆.
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DOI：
10.1016/j.lungcan.2015.11.004
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Horn L
中科院分区：
文献类型：
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作者：
Hames ML;Chen H;Iams W;Aston J;Lovly CM;Horn L
KRAS 突变是非小细胞肺癌 (NSCLC) 腺癌组织学患者中最常见的突变。 KRAS 突变对晚期 NSCLC 患者的临床影响尚不明确。我们试图确定 KRAS 突变状态、对细胞毒性化疗的反应以及转移性或复发性 NSCLC 患者的生存率之间是否存在相关性。对转移性或复发性 NSCLC 患者和肿瘤突变分析患者对常规化疗的反应进行分析。通过 SNaPshot 测定评估肿瘤突变的存在或不存在，该测定可检测包括 KRAS 在内的 8 个基因中超过 40 种体细胞突变。单独进行ALK荧光原位杂交分析。评估了 KRAS 突变状态与化疗反应和生存之间的关联。我们确定了 80 名患有转移性或复发性 NSCLC 且具有 KRAS 激活突变的患者，并将这些患者与 70 名全阴性患者（通过 SNaPshot 检测未检测到突变且 ALK 阴性）进行了比较。与泛突变阴性患者相比，KRAS 突变晚期 NSCLC 患者对一线化疗的无进展生存期显着缩短（4.5 个月与 5.7 个月，p = 0.008）。与没有 KRAS 激活突变的患者相比，KRAS 突变的晚期 NSCLC 患者的总生存期也显着缩短（8.8 个月 vs 13.5 个月，p = 0.038）。在这项单一机构回顾性分析中，与患有 KRAS 突变的晚期 NSCLC 患者相比，患有 KRAS 激活突变的晚期 NSCLC 患者对细胞毒性化疗的反应较差，且生存率较低。
KRAS mutations are the most commonly found mutations in patients with non-small cell lung cancer (NSCLC) adenocarcinoma histology. The clinical implications of KRAS mutations in patients with advanced NSCLC are not well defined. We sought to determine if there is a correlation between KRAS mutation status, response to cytotoxic chemotherapy, and survival in patients with metastatic or recurrent NSCLC. Patients with metastatic or recurrent NSCLC and tumor mutation analyses were analyzed for response to conventional chemotherapy. The presence or absence of tumor mutations was assessed with the SNaPshot assay, which detects >40 somatic mutations in eight genes, including KRAS. ALK fluorescence in-situ hybridization analysis was done separately. Associations between KRAS mutation status and response to chemotherapy and survival were assessed. We identified 80 patients with metastatic or recurrent NSCLC and a KRAS activating mutation, and we compared these patients to 70 patients who were pan negative (no detectable mutation by the SNaPshot assay and ALK negative). Patients with KRAS-mutant advanced NSCLC demonstrated a significantly shorter progression-free survival in response to first line chemotherapy (4.5 months versus 5.7 months, p = 0.008) compared to pan-mutation negative patients. Overall survival was also significantly shorter in patients with KRAS-mutant advanced NSCLC compared to patients without KRAS activating mutations (8.8 months versus 13.5 months, p = 0.038). Within this single institution retrospective analysis, patients with advanced NSCLC and a KRAS activating mutation exhibited inferior responses to cytotoxic chemotherapy and decreased survival compared to patients with advanced NSCLC and no KRAS mutation.