TACE联合索拉非尼治疗原发性肝癌合并不同分型门静脉癌栓的临床观察

Clinical observation of transcatheter arterial chemoembolization plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis

目的 探讨经导管肝动脉化疗栓塞术（TACE）联合索拉非尼治疗原发性肝癌合并不同类型门静脉癌栓（PVTT）的疗效及预后.方法 2009年4月至2011年6月,中山大学附属第三医院32例原发性肝癌合并PVTT患者行TACE术,术后3～7d开始服用索拉非尼治疗,剂量为400 mg,每日2次.32例患者,以PVTT分布范围分为3组：A组10例,侵犯门静脉主干;B组10例,侵犯门静脉一级分支（门静脉左支或右支）;C组12例,侵犯门静脉二级及以上分支.随访观察指标包括疾病稳定率（DCR,按照RECIST修订标准）、总生存时间（OS）、疾病进展时间（TTP）、不良反应以及联合治疗后1个月的肝功能血清学指标水平变化.统计学分析3组间DCR、OS、TIP差异.结果 3组患者联合治疗前基线资料差异均无统计学意义（均P ＞0.05）.3组患者联合治疗后2个月DCR分别为20.0％,70.0％,91.7％;中位OS分别为3、9、14个月;中位TTP分别为0、3、6个月.统计学分析显示,B、C组DCR均高于A组（均P＜0.05）,中位OS及中位TTP也均长于A组（均P＜0.05）.3组患者联合治疗后1个月的肝功能血清学指标水平与治疗前比较差异均无统计学意义（均P＞0.05）.不良反应包括手足皮肤反应23例、高血压3例、腹泻25例、脱发12例、口腔溃疡1例、消化道出血2例.其中3级不良反应为手足皮肤反应3例、腹泻3例.结论 TACE联合索拉非尼治疗原发性肝癌合并PVTT是安全的,可能延长门静脉一级及以上分支癌栓患者的OS及TTP.

Objective To explore the efficacy and safety of transcatheter arterial chemoembolization （TACE） plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis.Methods A total of 32 patients of advanced hepatocellular carcinoma with tumor thrombosis in portal vein were retrospectively analyzed.All of them took oral sorafenib after TACE.They were divided into 3 groups according to imaging examinations of tumor thrombosis in portal vein.Tumor thrombosis in main portal vein was group A,tumor thrombosis in right/left portal branch group B and tumor thrombosis in the second branch of portal vein group C.Tumor response rate,disease control rate （DCR）,overall survival （OS） and time to tumor progression （TTP） was followed up.Liver functions were compared with the pre-treatment level.The occurrences of adverse events were recorded.Results DCR was 20.0% （Group A）,70.0% （Group B） and 91.7 % （Group C） at 2 months post-treatment.DCR in groups B and C had significant differences with group A （P 〈 0.05）.The median OS was 3 （Group A）,9 （Group B） and 14months （Group C） and the median TTP 0 （Group A）,3 （Group B） and 6 months （Group C） respectively.The median OS and median TTP were significantly longer in Groups B and C than those in Group A （P 〈0.05）.Liver function at 2 months post-treatment had no statistical difference with the baseline.The most common adverse effects included hand foot skin reaction （n =23,3 cases of grade 3）,hypertension （n =3）,diarrhea （n =25,3 cases of grade 3）,hair loss （n =12）,oral ulcers （n =1） and gastrointestinal bleeding （n =2）.Conclusion The combined use of TACE and sorafenib is both safe and efficacious in the treatment of advanced hepatocellular carcinoma with tumor thrombosis in portal vein.And it may prolong OS and TTP in hepatocellular carcinoma with tumor thrombosis in right/left portal vein and second branch of portal vein.