粒子植入放疗联合肝动脉化疗栓塞治疗肝癌的临床研究

Iodine-125 seed implantational radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

目的观察局部125I粒子植入放疗联合肝动脉化疗栓塞(TACE)治疗肝细胞性肝癌疗效和患者耐受性。方法56例患者先采用TACE治疗1-3次,再行CT引导下125I粒子植入放疗。125I粒子植入12周后采用世界卫生组织标准评价疗效,采用美国国立癌症研究所毒性标准和美国放疗肿瘤组毒副反应评价标准评价急慢性肝脏毒副反应及其他毒副反应。结果56例中部分缓解18例,稳定36例,进展2例。全组中位生存时间31个月,1、3年生存率分别为88%、54%。1、3年局部控制率分别为93%、70%。1、3年远处转移率分别为9%、13%。单因素分析表明T分期、门脉癌栓、放疗前肝硬化Child-pugh分级、肿瘤数目和125I粒子空间排列对生存率有影响。多因素分析显示125I粒子空间排列、肿瘤数目和肝硬化Child-pugh分级是患者预后独立影响因素。5例发生急性肝脏毒副反应,1级2例,3级3例。9例出现1级上消化道急性损伤,其中1例出现轻度上消化道出血,8例表现为恶性、呕吐。10例出现1、2级外周血白细胞降低。2例出现放射性肝病。结论局部125I粒子植入放疗联合TACE综合治疗安全、有效,值得进一步研究。

Objective To evaluate the response and tolerance in hepatocellular carcinoma（HCC） patients treated by the iodine-125 seed implantational local radiotherapy combined with transcatheter arterial chemoembolization（TACE）. Methods Fifty-six HCC patients confirmed by cytology, AFP or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received iodine-125 seed implantation guided by CT after an interval of about one month. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after iodine-125 seed implantation. Irradiation toxicity were scored by the RTOG criteria. Acute liver toxicity was graded according to the common toxicity criteria （CTC） of National Cancer Institute. Late toxicity was focused on radiation-induced liver disease （RILD）. Results Partial response was observed in 18 patients. Stable disease and progressive disease was observed in 36 patients and 2 patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 3-year was 88% , 54%, respectively with a median survival period of 31 months. The 1-, 3-year local progression-free rate was 93%, 70%, respectively. The 1-, 3-year distant metastasis rate was 9%, 13%. Univariatc analysis showed that favorable prognostic predictors for survival were T3 stage, absence of portal thrombosis, Child-Pugh grade A and tumor irradiation dose of 〉 90 Gy. Tumor irradiation dose, the umber of tumor and liver cirrhosis were identified by Cox-regression analysis as independent predictors for survival. Two patients experienced CTC grade 1 acute hepatic toxicity and three patients experienced grade 3 acute hepatic toxicity. Two patients developed RILD. Nine patients experienced RTOG grade 1 acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia and five patients experienced grade 2 leucopenia. Conelusion Iodine-125 seed local radiotherapy combined with TACE is safe and effective for HCC. It is worth of further dose escalation study.