血清细胞角蛋白19在预测进展期非小细胞肺癌患者化疗疗效及预后中的临床意义

Clinical Significance of Serum Cytokeratin 19 Fragment in the Prediction of Chemotherapy Efficacy and Prognosis in Patients with Advanced Non-small Cell Lung Cancer

背景与目的由于RECIST(Response Evaluation Criteria in Solid Tumors, RECIST)标准不能对存活肿瘤组织进行检测,也不能对所有无法测量病灶的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者的疗效进行准确评估,本研究通过检测进展期NSCLC患者化疗前后血清细胞角蛋白19片段(cytokeratin 19 fragment, CYFRA21-1) 表达水平的变化以评价其在预测进展期NSCLC患者化疗疗效及预后中的临床价值。方法采用全自动生化分析仪电化学发光免疫法检测112例初治的NSCLC患者化疗前和化疗2周期后血清CYFRA21-1表达水平的变化,应用受试者特征工作曲线(receiver operating characteristics curve, ROC)评价血清CYFRA21-1反应在诊断影像学缓解(objective response, OR)中的效能及其与预后的相关性。结果经一线铂类为基础的两药联合方案化疗2周期后,血清CYFRA21-1水平较化疗前基线水平明显下降。80例可评价影像学和血清学疗效的患者中,26.3%(21/80)的患者达到影像学OR。化疗2周期后40.0%(32/80)的患者血清CYFRA21-1水平下降≥60%(血清CYFRA21-1反应)。血清CYFRA21-1反应与影像学OR之间有明显的统计学相关性(P<0.001)。所有患者的中位生存期为9.9个月,血清CYFRA21-1水平下降≥60%患者的生存期明显长于CYFRA21-1水平下降<60%的患者(12.3个月 vs 8.9个月,P<0.001)。单因素分析结果显示,血清CYFRA21-1基线水平、CYFRA21-1反应、PS评分及影像学OR是影响生存期的重要预后因素。Cox多因素生存分析证实,仅血清CYFRA21-1基线水平、CYFRA21-1反应及PS评分是影响预后生存期的独立因素,而OR则与预后无关。结论血清CYFRA21-1水平可敏感地反映影像学肿瘤体积大小的变化,可能是评价进展期NSCLC患者化疗疗效的替代指标,同时也是预测预后生存期的可信指标。

Background and objective RECIST （Response Evaluation Criteria in Solid Tumors） criteria could not be used to detect viable tumor tissue and is not an accurate tool for evaluation of objective response （OR） in non-small cell lung cancer （NSCLC） patients without measurable lesions. The aim of this study is to detect the pre-and post-chemotherapy serum cytokeratin 19 fragment （CYFRA21-1） expression levels in advanced NSCLC patients to evaluate the clinical value of CYFRA21-1 in the prediction of chemotherapy response and prognosis in NSCLC patients. Methods A automatic electrochemiluminescence immunoassay analyzer was applied to detect the pre-and post-chemotherapy serum CYFRA21-1 expression levels in 112 cases of initial treatment patients with NSCLC. Application of receiver operating characteristics curve （ROC） curve in evaluation the significance of serum CYFRA21-1 response in the diagnosis of OR and its correlation with prognosis. Results After 2 cycles of platinum-based combined chemotherapy, post-chemotherapy serum CYFRA21-1 significantly decreased compared with baseline levels. 80 patients were evaluable for radiological and serological efficacy, and 26.3% （21/80） patients achieved radiological OR. The decrease ratio of post-chemotherapy serum CYFRA21-1 with CYFRA21-1 response was 40.0% （32/80）. There was significant correlation between serum CYFRA21-1 response and OR （P〈0.001）. The median survival time of all patients was 9.9 months; the survival of patients with CYFRA21-1 response were significantly longer than those without CYFRA21-1 responders （12.3 months vs 8.9 months, P〈0.001）. Univariate survival analysis showed that PS score, OR, baseline serum CYFRA21-1 level and CYFRA21-1 response were important prognostic factors. Cox multivariate survival analysis confirmed that only the PS score, serum CYFRA21-1 baseline levels and CYFRA21-1 response were indepen-dent prognostic factors of NSCLC patients; OR was not an independent prognostic factor. Conclusion Serum CYFRA21-1 level can be sensitive to reflect changes in tumor volume, which may be a reliable substitution index for evaluation the chemotherapy efficacy in advanced NSCLC patients and a good indicator for prediction the prognosis of survival.