CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients
CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients
复制标题
DOI：
10.1007/s13277-015-3269-6
复制
发表时间：
2015-08-01
期刊：
影响因子：
--
通讯作者：
Tiseo, Marcello
中科院分区：
文献类型：
--
作者：
Facchinetti, Francesco;Aldigeri, Raffaella;Tiseo, Marcello
考虑到癌胚抗原（CEA）血清水平作为化疗治疗期间潜在有用的预测标志物的作用，我们研究了其在接受表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗的晚期非小细胞肺癌（NSCLC）患者中的适用性。我们的回顾性队列包括79例受晚期NSCLC影响的患者（33例EGFR突变和46例EGFR野生型或未知），这些患者在TKI治疗开始时和治疗第一个月后的CEA血清值可用，无论治疗线如何。根据EGFR突变状态，基线CEA值、1个月后CEA降低的百分比以及1个月后CEA降低20%的患者百分比（CEA应答）与疾病控制率（DCR）、无进展（PFS）和总（OS）生存率相关。EGFR突变患者的中位基线CEA水平（40.9 ng/ml;四分位距（IQR）8.9-197.6）显著高于野生型患者（6.2 ng/ml; IQR 2.8-12.8; p = 0.003）。突变型患者的CEA水平降低百分比（-10.7 vs.+13.4%）和CEA应答病例百分比（42 vs. 20%）均显著高于野生型/未知患者（分别为p = 0.007和p = 0.027）。在野生型/未知患者中，CEA应答与DCR显著相关，（p = 0.001），并且在单变量中均作为PFS的显著预测因子（p = 0.002）和多变量分析（风险比（HR）0.27; 95%置信区间（CI）0.11-0.66; p = 0.004）;仅发现OS预测的趋势（p = 0.082）。在EGFR突变组中，CEA降低与PFS或OS均未显示任何相关性。EGFR-TKI治疗1个月后的CEA应答可能是一个有用的标志物，值得进一步研究，作为EGFR野生型/未知NSCLC病例治疗结果的早期预测因子，尚未获得分子预测因子。
Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with a parts per thousand yen20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available.