应用CT灌注成像观察益气除痰方加减治疗中晚期非小细胞肺癌的疗效

Efficacy Observation of Modified Yiqi Chutan Recipe Treating Mid-late Stage NSCLC Patients by CT Perfusion

目的应用多层螺旋CT灌注成像(CT perfusion,CTP)技术,观察益气除痰方加减对非小细胞肺癌(non-small cell lung cancer,NSCLC)瘤内血流灌注的影响,同时评价CTP各项参数变化与预后的关系。方法将87例中晚期NSCLC患者按1:1随机分为中药(参一胶囊加益气除痰方)联合化疗组(治疗组,44例)和单纯化疗组(对照组,43例),两组均21天为1个疗程,共4个疗程。分别于治疗前、治疗2、4个疗程后进行常规CT(平扫+增强)检查,并对原发肿瘤进行CTP成像,测定肿瘤的大小及CTP各项灌注参数[包括血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(mean transit time,MTT)、到达峰值时间(time to peak,TP)及表面渗透性(permeability surface,PS)],分析比较治疗前后肿瘤大小及各项灌注参数的变化,同时评估CTP参数变化和预后及疗效的关系。结果 87例患者脱落7例,可评价80例,其中治疗组40例,对照组40例。(1)治疗后治疗组缓解率为47.5%(19/40),总稳定率为77.5%(31/40),对照组缓解率为40.0%(16/40),总稳定率为65.0%(26/40),两组缓解率及总稳定率比较,差异均无统计学意义(χ~2=0.672、1.227,P>0.05)。(2)与本组治疗前比较,治疗组治疗2、4个疗程后BF和PS值降低,MTT值升高(均P<0.05),对照组治疗2个疗程后BF和PS值降低,MTT值升高(均P<0.05)。与对照组同期比较,治疗组治疗4个疗程后BF值降低更明显(P<0.05)。(3)治疗4个疗程后,根据RECIST标准将患者分为缓解组(35例)和未缓解组(45例)。与本组治疗前比较,治疗后缓解组BV、BF和PS值均下降,MTT值升高(均P<0.05),未缓解组BF值升高(P<0.05)。(4)根据治疗后BF值的变化将患者分为BF值升高组(34例)和BF值降低组(46例),结果显示BF值升高组中位生存期246天,1年累计生存率13.0%,BF值降低组中位生存期387天,1年累计生存率53.1%;与BF值升高组比较,BF值降低组生存期延长,1年累计生存率提高,差异有统计学意义(χ~2=19.057,P<0.01)。结论参一胶囊加益气除痰方的中医药治疗可减少中晚期NSCLC的血流灌注量,改善血管的通透性,与化疗药物有良好的协同作用。CTP不仅反映了治疗前后的瘤体大小变化,而且反映了肿瘤血管的功能变化。同时,CTP参数的变化与预后关系密切,治疗后BF值下降者预后较好,生存期较长。

Objective To observe the effect of Modified Yiqi Chutan Recipe（MYCR） on blood flow perfusion in treating mid-late stage non-small cell lung cancer（NSCLC） patients by using multislice CT perfusion（CTP）,and to assess the relationship between each CTP parameter and the prognosis as well.Methods Totally 87 mid-late stage NSCLC patients were randomly assigned to the treatment group（44 cases,Shenyi Capsule＋MYCR＋chemotherapy） and the control group（43 cases,chemotherapy alone） in the ratio of 1：1.And 21 days consisted of 1 therapeutic course,4 courses in total.All of them underwent CTP of primary tumor and routine thoracic CT examination（plain CT and enhancement CT） 3times（before therapy,after 2 and 4 cycles）.CT findings were analyzed for tumor size and perfusion parameters[blood flow（BF）,blood volume（BV）,permeability surface（PS）,mean transit time（MTT）,and time to peak（TP） before and after treatment,and relationship between perfusion parameters and prognosis was also assessed.Results In 87 cases,7 dropped out and 80 cases were available,40 in the treatment group and 40 in the control group.（1） The relief rate was 47.5%（19/40） and the total stable rate was 77.5%（31/40） in the treatment group,and they were 40.0%（16/40） and 65.0%（26/40） in the control group,with no statistical difference between the two groups（x^2 =0.672,1.227;P〉0.05）.（2） Compared with before treatment group in the same group,BF and PS decreased,and MTT increased in the two groups after 2 and 4 courses（P 〈0.05）;BF and PS decreased,and MTT increased in the control group after 2 courses（P 〈0.05）.Compared with the control group after 4 courses,BF decreased more significantly in the treatment group（P 〈0.05）.（3） After 4 courses,all patients were assigned to the remission group（35 cases） and the non-remission group（45 cases） according to the RECIST standard.Compared with before treatment in the same group,BV,BF,and PS all decreased,and MTT increased in the remission group after treatment（all P 〈0.05）;BF increased in the non-remission group after treatment（P〈0.05）.（4） All patients were assigned to the BF increase group（34 cases） and the BF decrease group（46 cases） according to changed BF values after treatment.Results showed the mean survival rate was 246 days in the BF increase group（the 1-year accumulative survival rate being13.0%） and 387 days in the BF decrease group（the 1-year accumulative survival rate being 53.1%）.The life span was prolonged and the 1-year accumulative survival rate was elevated in the BF increase group,with statistical difference as compared with the BF decrease group（x^2 =19.057,P〈0.01）.Conclusions Shenyi Capsule plus MYCR could reduce BF in mid-late stage NSCLC patients,improve vascular permeability,showing better synergistic effect with chemotherapy.CTP could not only reflect the change of tumor size,but also reflect vascular function of the tumor.Meanwhile,changes of CTP parameters were closely associated with prognosis.Patients with post-treatment decreased BF value had better prognosis and longer life span.