巨块型肝细胞癌SBRT联合TACE治疗临床观察

目的随着介入技术的进步和三维适形调强放疗(intensity modulated radiotherapy,IMRT)及体部立体定向放疗(stereotactic body radiotherapy,SBRT)等精确放疗技术的日益成熟,肝动脉栓塞化疗(transarterial chemoembolization,TACE)联合放射治疗已成为综合治疗中晚期肝癌的重要方法,但SBRT治疗巨块型肝癌的研究较少。本研究旨在探讨体部伽玛刀SBRT联合TACE治疗巨块型肝细胞癌(hepatocellular carcinoma,HCC)的疗效及预后影响因素。方法回顾性分析2011-01-02-2016-06-30武警湖北总队医院81例TACE治疗后超级伽玛刀(SGS-Ⅰ型)SBRT的巨块型HCC患者临床资料。采用实体瘤疗效评价标准(modified respond evaluation criteria in solid tumors,mRECIST)标准评价近期疗效,检测治疗前后甲胎蛋白(alpha fetal protein,AFP)和谷丙转氨酶(alanine aminotransferase,ALT)水平,同时对患者进行远期随访并分析总生存期(overall survival,OS)及1、3、5年生存率。采用RTOG/EORTC标准评价毒副作用。结果81例患者均可评价疗效,1、3和5年随访率分别为100%、100%和59.26%。SBRT治疗结束后2~3个月复查CT,完全缓解(CR)29例,部分缓解(PR)48例,稳定(SD)2例,进展(PD)2例,总有效率为95.06%。1年局部控制率为71.60%。1、3、5年生存率分别为81.48%、40.74%和16.67%,中位生存时间15.0个月,95%CI:10.1~19.8个月;无疾病进展中位时间为11.0个月,95%CI:9.5~14.4个月。治疗后的AFP为(85.53±21.36)μg/L,低于治疗前的(635.62±125.83)μg/L,差异有统计学意义,t=8.189,P=0.002;治疗前后ALT水平分别为(70.34±16.60)和(54.95±12.02)U/L,差异无统计学意义,t=1.348,P=0.624。多因素分析结果显示,无门脉癌栓(HR=0.46,95%CI:0.16~0.64,P=0.016)和肝功能Child-Pugh分级A级是预后的影响因素(HR=3.45,95%CI:1.76~6.05,P=0.013)。亚组分析肿瘤临床靶体积(clinical target volume,CTV)≥120 cm^3与CTV<120 cm^3的1年局部控制率分别为72.03%和71.17%,中位生存期分别为16和14个月,差异均无统计学意义,均P>0.05。毒副作用主要为消化道反应、乏力及放射性肝损伤,均为1~2级,对症处理后缓解。结论SBRT联合TACE治疗巨块型HCC临床疗效显著,毒副作用轻微,值得临床推广应用。

Clinical effect and prognosis of stereotactic body radiotherapy combined with TACE for massive hepatocellular carcinoma

OBJECTIVE With the development of interventional therapy and precise radiotherapy,such as three-dimensional conformal intensity modulated radiation therapy and stereotactic body radiotherapy(SBRT),transarterial chemoembolization(TACE)combined with radiotherapy has become an important method to comprehensive treatment of advanced liver cancer,but there are few studies on the treatment of massive hepatocel-lular carcinoma(HCC)by SBRT.In the study,we investigate the effect and prognostic factors of body gamma knife SBRT combined with TACE in the treatment of massive HCC.METHODS A retrospective analysis was conducted on 81 patients with massive HCC who received super-gamma-knife(type SGS-Ⅰ)SBRT after TACE treatment between January 2,2011 and June 30,2016.The curative effect was evaluated by mRECIST criteria,The levels of alpha fetoprotein(AFP)and alanine aminotransferase(ALT)were measured before and after treatment,and patients were followed up for overall survival(OS)and 1,3 and5-year survival rates.The adverse reaction was evaluated by RTOG/EORTC criteria.RESULTS A total of 81 patients could be evaluated,among whom 29 obtained completely response,48 obtained partial response,2 reached stable status and2 was still in progress with the total response rate of 95.06%.One year local control rate was 71.60%.The overall survival rates of 1,3 and 5-year were 81.48%,40.74%and 16.67%,respectively.The median survival time was 15.0 months(95%CI:10.1-19.8 months);Progression-free time was 11.0 moths(95%CI:9.5-14.4 moths).The level of AFP after treatment was(85.53±21.36)μg/L,lower than(635.62±125.83)μg/L before treatment with significant statistical difference(t=8.189,P=0.002).The levels of ALT were(70.34±16.60)U/L and(54.95±12.02)U/L without significant difference(t=1.348,P=0.624).Multivariate analysis showed that absence of portal vein tumor thrombus was a favorable prognostic factors of OS(HR=0.46,95%CI:0.16-0.64,P=0.016),while Child-Pugh grade A of liver function was an adverse factor for prognosis(HR=3.45,95%CI:1.76-6.05,P=0.013).One year local control rate and the median survival time were 72.03%,71.17%and 16,14 months respectively between clinical target volume(CTV)≥120 cm3 subgroup and CTV<120 cm3 subgroup,there were no statistical difference(all P>0.05).The main adverse reactions during treatment were gastrointestinal reactions,fatigue and radioactive liver injury,mainly in grade 1-2,and all could be releaved by symptomatic treatment.CONCLUSION SBRT with supergamma-knife combined with TACE in the treatment of massive hepatocellular carcinoma has a significant clinical effect and mild side effects,which is worthy of clinical promotion and application.