1130例非小细胞肺癌手术患者术前血清CEA水平预后价值的倾向性匹配研究

发布时间：2018-12-27 10:08

【摘要】：原发性肺癌是全球范围内发病率和病死率最高的癌症,其中85%为非小细胞肺癌(NSCLC)。临床对NSCLC患者远期生存风险的准确评估,有利于正确选择治疗方案和制定随诊计划。癌胚抗原(CEA)是NSCLC患者最常用的肿瘤标记物,广泛用于NSCLC的辅助诊断和疗效监测。研究表明,血清CEA水平对NSCLC患者远期预后有预测价值,但目前缺乏大样本、设计良好的临床研究为此提供高循证级别证据。目的通过临床大样本队列研究,探讨NSCLC患者术前血清CEA水平的远期预后价值,并应用循证医学方法,为研究结论提供高循证医学级别的证据。方法本研究为回顾性队列研究,连续纳入2006年7月至2011年6月在大连医科大学附属第一医院胸外科接受手术治疗的NSCLC患者1130例,根据患者术前血清CEA水平分为两组,探究术前血清CEA水平对远期预后的预测价值,并通过倾向性评分匹配(PSM)控制混杂变量组间差异,提升研究结论的可靠性,再通过累积Meta分析的方法将研究结果与既往发表的研究结果进行合并,以提供最高循证级别的临床证据。结果1130患者中位生存期为44(0-61)个月,总体生存率为47.1%;中位无病生存时间为35(0-61)个月,未复发率为46.3%。两组患者总体生存时间(p=0.004)和无病生存时间(p=0.009)有统计学差异;倾向性评分匹配后,两组患者逐渐混杂因素匹配良好,预后差值明显减小,术前血清CEA水平仍能够影响远期预后;COX模型单因素分析显示高CEA患者远期死亡HR=1.595(95%CI1.329-1.863,p=0.004),复发风险HR=1.498(95%CI 1.271-1.881,p=0.004);COX模型多因素分析显示,高CEA患者远期死亡HR=1.586(95%CI 1.398-1.812,p=0.016),复发风险HR=1.413(95%CI 1.22-1.734,p=0.022);累积Meta分析显示本研究总体生存风险HR与既往研究总体HR合并后,总体生存和无病生存的累积HR均与前相仿,且具有统计学意义。结论(1)队列研究表明:术前血清CEA水平可以作为总体生存期和无病生存期的独立影响因素之一。(2)倾向性评分匹配提供的更高循证级别证据表明:对于无差别的NSCLC患者总体,术前血清CEA水平影响患者远期预后,CEA高的患者预后差。(3)累积Meta分析最高循证级别证据表明:术前血清CEA水平对术后总体生存风险和无病生存风险均有预测价值。
[Abstract]:Primary lung cancer is the highest morbidity and fatality rate in the world, 85% of which are non-small cell lung cancer (NSCLC). Accurate assessment of long-term survival risk in patients with NSCLC is beneficial to correct treatment and follow-up plan. Carcinoembryonic antigen (CEA) is the most commonly used tumor marker in patients with NSCLC. Studies have shown that serum CEA levels can predict the long-term prognosis of NSCLC patients, but there is a lack of large samples at present, and well-designed clinical studies provide high evidence-based evidence for this purpose. Objective to evaluate the long-term prognostic value of serum CEA levels in patients with NSCLC by a large clinical cohort study and to provide evidence of high Evidence-Based Medicine (EBM) grade for the conclusions of Evidence-Based Medicine (EBM). Methods A retrospective cohort study was conducted in 1130 NSCLC patients who received surgical treatment in thoracic surgery of the first affiliated Hospital of Dalian Medical University from July 2006 to June 2011. The patients were divided into two groups according to the preoperative serum CEA level. To explore the predictive value of preoperative serum CEA level for long-term prognosis, and to control the differences between confounding variables by matching (PSM) with tendentiousness score, so as to improve the reliability of the study conclusions. The results were combined with previously published results by cumulative Meta analysis to provide the highest level of evidence-based clinical evidence. Results the median survival time of 1130 patients was 44 (0-61) months, the overall survival rate was 47.1, the median disease-free survival time was 35 (0-61) months, and the non-recurrence rate was 46.3%. There were significant differences between the two groups in total survival time (p0. 004) and disease-free survival time (p0. 009). After the tendentiousness score matching, the two groups gradually mixed factors matched well, and the difference of prognosis was obviously reduced. The preoperative serum CEA level could still affect the long-term prognosis. Univariate analysis of COX model showed that HR=1.595 (95CI1.329-1.863p0.004) and HR=1.498 (95%CI 1.271-1.881p0.004) were long-term mortality in patients with high CEA. The multivariate analysis of COX model showed that HR=1.586 (95%CI 1.398-1.812) and HR=1.413 (95%CI 1.22-1.734) were long-term mortality (95%CI 1.398-1.812) and HR=1.413 (95%CI 1.731.734) in patients with high CEA. Cumulative Meta analysis showed that the cumulative HR of total survival and disease-free survival were similar to those of previous studies after the combination of HR and HR. Conclusion (1) the cohort study showed that preoperative serum CEA level could be one of the independent factors of overall survival and disease-free survival. There was no difference in the overall number of NSCLC patients, Preoperative serum CEA level affects the long-term prognosis of patients, and the prognosis of patients with high CEA is poor. (3) the cumulative Meta analysis of the highest evidence-based evidence shows that preoperative serum CEA level can predict the overall survival risk and disease-free survival risk.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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