Hames Megan L, Chen Heidi, Iams Wade, Aston Jonathan, Lovly Christine M, Horn Leora
Department of Pharmaceutical Sciences, Vanderbilt University Medical Center (VUMC) 1211 Medical Center Drive, Nashville, TN 37232, United States.
Department of Cancer Biostatistics, Vanderbilt-Ingram Cancer Center (VICC)/Vanderbilt University Medical Center (VUMC) 2220 Pierce Avenue, 625 Preston Research Building, Nashville, TN 37232, United States.
Lung Cancer. 2016 Feb;92:29-34. doi: 10.1016/j.lungcan.2015.11.004. Epub 2015 Nov 10.
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.
KRAS 突变是肺非小细胞癌（NSCLC）腺癌组织学患者中最常见的突变类型。KRAS 突变在晚期 NSCLC 患者中的临床意义尚不明确。我们试图确定转移性或复发性 NSCLC 患者的 KRAS 突变状态、对细胞毒性化疗的反应和生存率之间是否存在相关性。
对转移性或复发性 NSCLC 患者及肿瘤突变分析进行常规化疗反应分析。采用 SNaPshot 检测法评估肿瘤突变的有无，该检测法可检测包括 KRAS 在内的 8 个基因中的>40 种体细胞突变。ALK 荧光原位杂交分析单独进行。评估 KRAS 突变状态与化疗反应和生存率之间的关联。
我们确定了 80 例转移性或复发性 NSCLC 且有 KRAS 激活突变的患者，并将这些患者与 70 例全阴性患者（SNaPshot 检测法未检测到突变且 ALK 阴性）进行比较。与全突变阴性患者相比，KRAS 突变的晚期 NSCLC 患者对一线化疗的无进展生存期明显缩短（4.5 个月对 5.7 个月，p = 0.008）。与无 KRAS 激活突变的患者相比，KRAS 突变的晚期 NSCLC 患者的总生存期也明显缩短（8.8 个月对 13.5 个月，p = 0.038）。
在这项单机构回顾性分析中，与无 KRAS 突变的晚期 NSCLC 患者相比，有 KRAS 激活突变的晚期 NSCLC 患者对细胞毒性化疗的反应较差，生存率降低。
