Servicio de Oncología Médica, Hospital General Universitario, Valencia, Spain.
Lung Cancer. 2011 Jun;72(3):365-9. doi: 10.1016/j.lungcan.2010.09.005. Epub 2010 Nov 12.
Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients.
We examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination.
The median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p=0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p=0.514).
In advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS.
血液中循环 DNA 的定性分析是一种很有前途的非侵入性诊断和预后工具。我们的目的是研究 KRAS 密码子 12 点突变的存在与晚期非小细胞肺癌（NSCLC）患者的几个临床变量之间的关系。
我们检查了 308 名接受顺铂和多西他赛治疗的 IIIB 和 IV 期 NSCLC 患者。在化疗前采集血液样本，并使用商业吸附柱从血浆中提取循环 DNA。KRAS 突变状态通过基于等位基因鉴别法的 RT-PCR 方法确定。
患者的中位年龄为 60 岁[31-80]，84%为男性，98%的体能状态为 0-1，84%的患者为 IV 期。组织学亚型如下：30%为鳞状细胞癌（SCC），51%为腺癌（ADC），19%为其他类型。在 277 名可评价反应的患者中，1%达到完全缓解（CR），26%达到部分缓解（PR），34%疾病稳定（SD），39%疾病进展（PD）。此外，27（8.8%）名患者存在 KRAS 突变；26 名患者存在 KRAS 密码子 12 TGT 突变，1 名患者存在密码子 12 GTT 突变。血浆 DNA 中存在 KRAS 突变的患者中位无进展生存期（PFS）为 5.77 个月[3.39-8.14]，而 KRAS 野生型（wt）患者的 PFS 为 5.43 个月[4.65-6.22]（p=0.277）。KRAS 突变患者的中位总生存期（OS）为 9.07 个月[4.43-13.70]，而 wt 患者为 10.03 个月[8.80-11.26]（p=0.514）。
在晚期 NSCLC 患者中，血浆游离 DNA 中是否存在 KRAS 突变与基线特征、反应率、PFS 或 OS 均无显著差异。
