立体适形放射治疗联合肝动脉化疗栓塞治疗肝细胞性肝癌的临床研究

Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

目的观察立体适形放射治疗(3DCRT)联合肝动脉化疗栓塞(TACE)治疗肝细胞性肝癌(HCC)的疗效和患者的耐受性。方法46例HCC患者,先采用TACE治疗1～3次,再进行3DCRT。2Gy/次,每天1次,每周5d。肿瘤剂量30～54Gy,总疗程3～6周。放疗结束后采用世界卫生组织(WHO)标准评价疗效,采用美国国立癌症研究所(NCI)的毒性标准和美国放射治疗肿瘤组(RTOG)的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46例患者中,部分缓解(PR)8例,稳定(SD)35例,进展(PD)3例。全组患者中位生存时间16个月,1、2、3年生存率分别为60.9%、39.1%和28.3%。1、2、3年局部控制率分别为73.9%、56.5%和39.1%。1、2、3年远处转移率分别为15.2%、21.7%和34.8%。单因素分析表明,T分期、广州会议分期、门脉癌栓(PVT)、放疗前肝硬化Child Pugh分级和肿瘤照射剂量对生存率的影响有统计学意义。Cox多因素分析显示,肿瘤照射剂量和肝硬化Child Pugh分级是HCC患者预后的独立影响因素。5例患者发生急性肝脏毒副反应,1级2例,3级3例。3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。10例出现1或2级外周血白细胞降低。2例出现放射性肝病。结论3DCRT联合TACE综合治疗HCC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 three-dimensional conformal radiotherapy （3DCRT） combined with. transcatheter arterial chemoembolization （TACE）. Methods Fourty-six HCC patients confirmed by cytology or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received 3DCRT after an interval of about one month. 3DCRT was given with the field covering the tumor with a generous margin. 6 MV X-ray was used. The total dose was 30-54 Gy, in daily 2 Gy fractions. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after 3DCRT. Irradiation toxicities 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 8（ 17.4% ） patients. Stable disease and progressive disease was observed in 35（76. 1% ） patients and 3（6.5% ） patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 2- and 3-year was 60.9%, 39.1% and 28.3%, respectively, with a median survival period of 16 months. The 1-, 2- and 3-year local progression-free rate was 73.9%, 56.5% and 39.1%, respectively. The 1-, 2- and 3-year distant metastasis rate was 15.2% , 21.7% and 34.8%. Univariate analysis showed that favorable prognostic predictors for survival were： T3 stage, CACA 2001 stage Ⅰ , absence of portal thrombosis, Child-Pugh grade A and irradiation dose of 〉45 Gy. Irradiation dose 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. Three patients experienced RTOG grade 1acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia , and five patients experienced grade 2 leucopenia . Conclusion 3DCRT combined with TACE is safe and effective for HCC. It is worthy of a further dose escalation study.