《中国癌症杂志》2010年第20卷第10期CHINA ONCOLOGY 2010 Vol.20 No.10769索拉非尼联合冷冻消融治疗进展期乙肝相关性肝细胞癌患者的疗效预测分析 ［摘要］　背景与目的：索拉非尼(Sorafenib)联合氩氦刀局部冷冻消融(argon-helium cryoablation)治疗进展期肝细胞癌(advanced hepatocellular carcinoma，AHCC)患者疗效确定，但患者之间的预后相差很大。

目前所采用的进展期肝癌预测系统(advanced liver cancer prognostic systems，ALCPS)、终末期肝病模型(model for end-stage liver disease，MELD)、Child-Pugh分级等评分系统对疗效的评价都有一定的意义，但对其优劣性缺乏相关的对比研究。

本研究采用上述系统对接受联合治疗的AHCC患者进行分层分析，以评价各个评分系统在联合治疗预后预测中的意义，为临床医生选择合适的治疗对象提供依据。

方法：50例进展期乙型肝炎相关性肝癌患者，给予索拉非尼联合氩氦刀局部冷冻消融治疗后，分别比较按照ALCPS、MELD、Child-Pugh评分系统划分的不同分值区间患者的疗效、生存期及疾病进展时间，分析各评分系统在预后评价中的意义。

结果：50例患者经治疗后中位总生存期(OS)为11.0个月、中位疾病进展时间(TTP)为6.0个月，其中2例(4％)患者获得完全缓解(CR)，8例(16％)部分缓解(PR)，23例(46％)病情稳定(SD)，治疗有效率达66％。

ALCPS评分≤8分、9～15分及≥16分的患者中位OS分别为16.5、8.6和6.8个月(P<0.05)，中位TTP分别为12.0、6.0和2.0个月(P<0.01)，治疗有效率分别为94.1％、70.6%和31.3%(P<0.01)。

MELD评分≤7分和>7分的患者中位OS分别为16.5和7.8个月(P<0.05)，中位TTP分别为10.0和2.5个月(P<0.05)；治疗有效率分别为78.8％和41.2%(P<0.01)；Child-Pugh A/B的患者OS及TTP差异无统计学意义(P>0.05)，治疗有效率分别为69.2％和54.6%(P>0.05)。

结论：ALCPS、Child-Pugh、MELD系统对AHCC患者治疗预后均有不同程度的预测意义，而ALCPS系统更能有效地预测AHCC的临床获益程度。

［关键词］　冷冻消融；　索拉非尼；　进展期肝细胞癌；　Child-Pugh分级；　终末期肝病模型；进展期肝癌预测系统 中图分类号：R735.7；R730.58 文献标识码：A 文章编号：1007-3639(2010)10-0769-06Therapeutic effects and prognostic analysis of Sorafenib combined with Cryoablation on hepatitis B-related advanced hepatocellular carcinoma LU Yin-ying,CHANG Xiu-juan,WANG Chun-ping,ZHOU Lin,CHEN Yan,WU Yu,QU Jian-hui,ZENG Zhen,BAI Wen-lin,YANG Yong-ping(Therapeutic Research Center of Hepatocarcinoma, 302 Hospital of PLA, Beijing 100039，China)Correspondence to：YANG Yong-ping　E-mail：yongpingyang@ ［Abstract］ Background and purpose：Recently, a few studies suggested that effective effects of Sorafenib combined argonhelium cryoablation on hepatitis B-related advanced hepatocellar carcinoma (AHCC) . However, the prognosis of the patients has a substantial difference. Advanced liver cancer prognostic systems (ALCPS), Model for endstage liver disease (MELD) and Child-Pugh scoring system has shown some value in the assessment of therapeutic effects for AHCC. Unfortunately, there were few comparative studies of these different scoring systems. This study was aimed to identify the potential predictive scoring system for the therapeutic response of argonhelium cryoablation when combined with sorafenib on hepatitis Brelated AHCC.Methods：Fifty patients with AHCC who underwent sorafenib combined with cryoablation were enrolled in this study. The therapeutic effect, overall median survival (OS) and time of progression (TTP) were compared in different groups and were later divided using Child-Pugh, model for endstage liver disease (MELD) and advanced liver cancer prognostic systems (ALCPS) scoring systems. The significance of predicting the prognoses by Child-Pugh, MELD and ALCPS scoring systems were respectively analyzed. Results：Median基金项目：国家重大专项基金资助项目(No：2008ZX10002-018)；军队医学杰出人才基金资助项目(No：04J020)。

通讯作者：杨永平　E-mail:yongpingyang@770陆荫英，等.　索拉非尼联合冷冻消融治疗进展期乙肝相关性肝细胞癌患者的疗效预测分析 在对进展期肝细胞癌(a d v a n c e d hepatocelluar carcinoma，AHCC)患者行氩氦刀局部冷冻消融的基础上联合甲苯磺酸索拉非尼全身治疗，取得了较好的疗效，延长了患者的生存期［1-2］，但患者之间的预后却相差很大(3.8～26.0个月)。

如何选择一个敏感而特异的评分系统，在治疗前对患者进行合理的评估，并有效预测治疗预后，使患者在现有医疗资源的前提下获益最大，有着重要的临床意义。

目前国内外在AHCC治疗术前评估方面报道较多的为Child-Pugh分级系统，一般主张A/B级的患者进行积极治疗，而C级患者行对症支持治 疗［3］，但Child-Pugh分级系统仅对肝功能进行评估，未能兼顾其他脏器功能及肿瘤的特征，有很大的缺陷。

由此本研究分别采用了进展期肝癌预测系统(advanced liver cancer prognostic systems，ALCPS)、终末期肝病模型(model for end-stage liver disease，MELD)、Child-Pugh分级系统对患者进行分层，用Kaplan-Meier法分析比较各系统在治疗预后预测中的临床意义，现报告如下。

1　资料和方法1.1　入选标准 2007年7月—2009年12月在我中心住院的50例乙肝相关性AHCC患者，诊断符合《原发性肝癌规范化诊治专家共识》［4］，按照巴塞罗那临床肝癌分期系统(Barcelona clinic liver cancer staging classification，BCLC)分期属于进展期肝癌［5］；入组前未接受过肝癌的overall survival (OS) and time of progression (TTP) were 11.0 months and 6.0 months, respectively. Complete response (CR) was observed in 2 patients (4%), partial response (PR) in 8 (16%), stable disease (SD) in 23 (46%) and therapeutic effective rate was 66%. According to the ALCPS, patients with a score of ≤8, 9-15 and ≥16 had different OS (16.5, 8.6, and 6.8 months, respectively (P <0.05), different TTP (12.0months, 6.0 months, and 2.0month, respectively (P <0.01) and different therapeutic effective rates (94.1%, 70.6%, and 31.3%, respectively (P <0.01) . OS and TTP of patients with a MELD score of ≤7 was 16.5 months and 10.0 months, which were longer than patients with a MELD score of >7 (7.8months, 2.5months) . The respective therapeutic effective rates were 78.2% versus 41.2% in the two groups. The OS and TTP of Child-pugh class A or B patients had no significant difference (P >0.05), but the therapeutic effective rates for Child-pugh class A patients were higher than that of class B patients (69.2% vs 54.6%, P >0.05). Conclusion ：Sorafenib combined with cryoablation on AHCC has advantages of prolonging OS and TTP. ALCPS, MELD and Child-Pugh scoring systems can be used to predict the feasibility and efficacy of that treatment on AHCC. ALCPS seems to be the most sensitive and specific predictor in patients with AHCC who underwent the treatment.　［Key words ］　Cryoablation; Sorafenib; Advanced hepatocellular carcinoma; Child-Pugh; MELD; ALCPS系统治疗。