肝脏微血管密度在索拉非尼联合冷冻消融治疗进展期肝癌疗效评价中的意义

目的探讨索拉非尼联合局部冷冻消融治疗进展期肝细胞癌(HCC)的疗效，评价肿瘤微血管密度(microvessel density, MVD)与HCC患者治疗预后的关系。方法102例进展期肝癌患者随机分为索拉非尼联合冷冻消融治疗组(S&C组, 50例)和冷冻消融治疗组(C组, 52例)，分别给予索拉非尼联合冷冻消融治疗及单独冷冻消融治疗，治疗终点为肿瘤进展或出现不能耐受的毒性；治疗前留取肝癌组织标本，并通过计数CD34免疫组化数值来评估肝癌组织微血管密度(MVD)，每4~6周按照RECIST标准进行疗效评价，随访生存期及肿瘤进展情况，分析肝癌组织MVD值与预后的关系。结果S&C组2例完全缓解(CR)，9例部分缓解(PR)，22例疾病稳定(SD)，疾病控制率(disease control rate，DCR)66%；C组4例PR，19例SD，DCR 44.2%(P=0.027)；S&C组患者中位生存期(OS)和中位肿瘤进展时间(TTP)分别为12.5和9.6个月，而C组患者仅为8.6和5.3个月(P=0.019)。CR&PR组的肝组织平均微血管密度(111/0.74 mm2)明显低于疾病进展组(339/0.74 mm2，P=0.000 1)。具有较低肝组织微血管密度的患者在接受索拉非尼联合氩氦刀冷冻消融联合治疗后其中位总生存期和中位肿瘤进展时间明显长于单纯氩氦刀冷冻消融组；具有较高肝组织微血管密度的患者其中位总生存期和中位肿瘤进展时间在两组治疗方式中无区别。结论索拉非尼联合局部冷冻消融治疗能显著延长进展期HCC患者的生存期及肿瘤进展时间，使进展期HCC患者临床获益；进展期肝癌患者肝组织中较高的微血管密度预示较差的治疗应答。

Liver microvessel density in evaluating therapeutic effect of sorafenib combined with argon-helium cryoablation in treatment of advanced hepatocellular carcinoma

[Abstract]ObjectiveTo investigate the therapeutic effect of argon-helium cryoablation combined with sorafenib on hepatitis B-related advanced hepatocellular carcinoma (HCC)and to evaluate the role of microvessel density (MVD) in prognostic evaluation. MethodsA total of 102 patients with advanced HCC were randomly divided into two groups, with 50 receiving sorafenib plus cryoablation(group S&C) and 52 receiving only cryoablation (group C). The endpoint of the treatment was tumor progression or untolerable adverse reaction. Tumor tissues were obtained before treatment. MVD was evaluated by immunohistochemical analysis using CD34 antibody. The therapeutic effects were evaluated according to RECIST criterion every 4-6 weeks. The adverse events were observed in both groups; the therapeutic effect, overall survival time(OS), and time to progression(TTP) were compared between two groups. MethodsIn group S&C, complete response (CR) was achieved in 2 patients(4%), partial response(PR)in 9 (18%), and stable disease(SD) in 22(44%), with the disease control rate(DCR) being 66%; in group C, no CR, PR in 4(7.6%), and SD in 19(36.5%), with the DCR being 44.2% (P<0.05). The overall survival (OS) and the time to progression (TTP) were significantly longer in group S&C than in group C (12.5 months vs 8.6 months, 9.6 months vs 5.3 months; P<0.01). The mean MVD in group CR&PR (111/0.74 mm2)was significantly lower than that in group PD(339/0.74 mm2, P<0.01). Patients with lower MVD receiving sorafenib plus cryoablation had longer OS and TTP than those only receiving cryoablation. The OS and TTP in patients with higher MVD had no significant difference between different groups. MethodsSorafenib plus cryoablation is a safe and effective therapy for patients with advanced HCC; it can improve the OS and TTP of patients. Patients with higher MVD have a lower response to therapy and poor prognosis.