β-CTX和N-MID对预测老年肺癌骨转移患者发生骨相关事件和总生存的临床价值  

Clinical value of β-CTX and N-MID as predictors for skeletal-related events and overall survival in elderly lung cancer patients with bone metastases

作　　者：乔丹[1] 王智煜[1] 文孝婷 李洪涛[1] 赵晖[1] 

机构地区：[1]上海交通大学附属第六人民医院肿瘤内科,上海200233

出　　处：《肿瘤》2015年第4期414-422,共9页Tumor

基　　金：国家自然科学基金资助项目(编号:81201628)~~

摘　　要：目的 :分析血清骨代谢标志物Ⅰ型胶原羧基端肽β特殊序列(βisomer of the C-terminal telopeptide of typeⅠcollagen,β-CTX)和骨钙素N-端中分子片段(N-terminal midfragment of osteocalcin,N-MID)在老年肺癌骨转移患者接受唑来膦酸治疗过程中的变化情况,探讨二者对老年肺癌骨转移患者临床预后的预测价值。方法:在本项前瞻性研究中,选取年龄>60岁的肺癌骨转移患者126例,肺癌无骨转移患者110例,同时入组的正常对照为89例。所有肺癌骨转移患者均应用唑来膦酸治疗,每4周1次(4 mg静脉滴注)。采用放射免疫法动态监测肺癌骨转移患者在治疗前和唑来膦酸治疗后2、4、6、8、10和12个月的血清β-CTX和N-MID水平,并记录研究期间患者发生骨相关事件(skeletal-related events,SREs)和总生存的情况。结果:肺癌骨转移组血清β-CTX和N-MID基线水平明显高于肺癌无骨转移组及正常对照组(P值均<0.001),而唑来膦酸治疗后肺癌骨转移组的β-CTX和N-MID水平较治疗前基线水平明显下降(P值均<0.01)。多因素分析结果显示,β-CTX和N-MID是影响SREs发生的独立危险因素[比值比(odds ratio,OR)=6.367,P=0.001;OR=3.015,P=0.025)。高水平β-CTX组发生SREs的中位时间和中位生存时间均短于低水平β-CTX组,差异均有统计学意义(6.0个月vs 10.5个月,P=0.031;13.0个月vs 16.5个月,P=0.028);高水平N-MID组发生SREs的中位时间也低于低水平N-MID组(6.5个月vs 10.5个月,P=0.046),但是二者的中位生存时间无明显差异(14.5个月vs 17.0个月,P=0.226)。结论:血清β-CTX和N-MID是预测老年肺癌骨转移患者发生SREs的有效指标,同时β-CTX可能对评估老年肺癌骨转移患者的预后有一定价值。Objective： To quantitatively measure the changes of β isomer of the C-terminal telopeptide of typeⅠ collagen（β-CTX） and N-terminal midfragment of osteocalcin（N-MID） levels in elderly lung cancer patients with bone metastases undergoing treatment withz oledronic acid, and to evaluate their predictive value in clinical prognosis of these patients.Methods： This was an observational and prospective study including 126 cases（a ged 〉60 years） of lung cancer with bone metastases, 110 caseso f lung cancer without bone metastases and 89 normal controls. All of cases with bonem etastases were treated with4 mg zoledronic acid by intravenous infusion every 4 weeksT. he serum β-CTX and N-MID levels were dynamically monitored by radioimmunoassay at baseline and2, 4, 6, 8, 10 and 12 months after the beginning of treatment. Data ons keletal-related events（SREs）development and overall survival were recorded.Results： At baseline, serum β-CTX and N-MID levels were significantly higher in patients with bone metastases than those in patients without bone metastasesa nd the normal controls（all P 〈 0.001）. Zoledronic acid resulted in a significant reduction of serum β-CTX and N-MID levels comparing with baseline（both P 〈 0.01）. Multivariate logistic regression analysis showed the elevated β-CTX and N-MID were risk factors of SREs [odds ratio（OR） =6.367, P = 0.001; OR = 3.015, P = 0.025]. The median time to SREs and median survival time（MST） of patients with elevated β-CTX were significantly shorter than those of patients with declined β-CTX（6.0 vs 10.5 months, P = 0.031; 13.0 vs 16.5 months, P = 0.028）. The median time to SREs in patients with elevated N-MID was significantly shorter than that in patients with declined N-MID（6.5 vs 10.5 months, P = 0.046）, but the MST in two groups had no signif cant difference（14.5 vs 17.0 months, P = 0.226）.Conclusion： Serum β-CTX and N-MID may be useful predictors for SREs in elderly lung cancer patients with bone metastases, and �

关 键 词：肺肿瘤 肿瘤转移 骨 纤维胶原类 骨钙素 β-CTX N-MID 唑来膦酸 

分 类 号：R734.2[医药卫生—肿瘤]