Circulating Cell-Free DNA in Plasma of Never Smokers with Advanced Lung Adenocarcinoma Receiving Gefitinib or Standard Chemotherapy as First-Line Therapy
Circulating Cell-Free DNA in Plasma of Never Smokers with Advanced Lung Adenocarcinoma Receiving Gefitinib or Standard Chemotherapy as First-Line Therapy
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DOI：
10.1158/1078-0432.ccr-11-0400
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发表时间：
2011-08-01
影响因子：
11.5
通讯作者：
Lee, Jin Soo
中科院分区：
文献类型：
--
作者：
Lee, Young Joo;Yoon, Kyong-Ah;Lee, Jin Soo
目的：研究循环游离DNA（CFDNA）作为多种癌症的潜在筛查或预后标志物。本研究探讨了其临床意义在一个同质组的肺癌patients.Experimental Design：我们分析了134个从不吸烟的晚期肺腺癌，谁参加了前瞻性随机III期研究（第一信号）比较吉非替尼与吉西他滨加顺铂（GP）作为一线治疗的血液样本。通过靶向人ACTB基因组序列的实时定量PCR测量血浆CFDNA的量。结果：基线血浆CFDNA水平与原发灶大小无相关性（P = 0.961），而转移灶数目与基线血浆CFDNA水平显著相关（P = 0.015）。在GP组中，低CFDNA组的缓解率低于中或高CFDNA组（分别为26.1%、57.9%和60.9%; P = 0.035）。然而，在吉非替尼组中，三个CFDNA组之间的缓解率没有差异（分别为57.1%、47.4%和51.9%; P = 0.825）。高三分位数CFDNA组的生存期显著短于低三分位数CFDNA组（中位总生存期分别为16.0和28.6个月; P = 0.030）。随着CFDNA水平的升高，患者死亡的危险性增加（HR = 1.23，95%CI，1.01-1.50; P = 0.045）。临床癌症研究; 17（15）; 5179-87。(C)2011年AACR。
Purpose: Circulating cell-free DNA (CFDNA) was investigated as potential screening or prognostic markers in a variety of cancers. This study investigated its clinical significance in a homogeneous group of lung cancer patients.Experimental Design: We analyzed the blood samples of 134 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy. The amount of plasma CFDNA was measured by real-time quantitative PCR targeting the human ACTB genomic sequence. The patients were divided into three groups according to the tertiles of baseline plasma CFDNA.Results: Baseline plasma CFDNA did not correlate with primary tumor size (P = 0.961), whereas the number of metastatic sites correlated significantly with baseline plasma CFDNA (P = 0.015). In the GP arm, the low-CFDNA group showed a lower response rate than the middle-or high-CFDNA group (26.1%, 57.9%, and 60.9%, respectively; P = 0.035). However, in the gefitinib arm, there was no difference in response rate between the three CFDNA groups (57.1%, 47.4%, and 51.9%; respectively; P = 0.825). The high tertile CFDNA group showed a significantly shorter survival than the low tertile CFDNA group (median overall survival, 16.0 vs. 28.6 months, respectively; P = 0.030). The risk of death increased with increased baseline plasma CFDNA (HR = 1.23, 95% CI, 1.01-1.50; P = 0.045).Conclusion: High plasma CFDNA is associated with aggressive tumor behavior and poor survival outcomes in these patients. Clin Cancer Res; 17(15); 5179-87. (C) 2011 AACR.