Sergio Adriana, Cristofori Chiara, Cardin Romilda, Pivetta Giorgio, Ragazzi Roberto, Baldan Anna, Girardi Lisa, Cillo Umberto, Burra Patrizia, Giacomin Anna, Farinati Fabio
Istituto Oncologico Veneto, Padova, Italy.
Am J Gastroenterol. 2008 Apr;103(4):914-21. doi: 10.1111/j.1572-0241.2007.01712.x. Epub 2008 Jan 2.
Although transcatheter arterial chemoembolization (TACE) is effective in hepatocellular carcinoma (HCC), it is not considered a curative procedure. Among the factors potentially interfering with its effectiveness is a hypothetical neoangiogenic reaction due to ischemia. In our study, we evaluated the changes in the levels of two angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [b-FGF]) and one parameter of invasiveness (urokinase-type plasminogen activator [uPA]) in patients treated with TACE.
Three blood samples were provided from 71 HCC patients undergoing TACE: before TACE (t0), after 3 days (t1), and after 4 wk, when they had spiral computed tomography (sCT) scanning (t2). The referring radiologists blindly evaluated tumor burden and vascularization at t0 and residual activity at t2. The choice of TACE as treatment was based on the American Association for the Study of Liver Diseases (AASLD) guidelines.
Complete response at sCT was recorded in 27% of patients; mean survival was 35 months (confidence interval [CI] 31-40) and the 4-yr survival was 57%. VEGF levels were significantly correlated with the number of nodes and were higher in nonresponders at t2 (P = 0.01); below-median VEGF levels predicted a longer survival (P = 0.008). b-FGF correlated with VEGF, tumor size, vascularization, and residual activity, showing a borderline correlation with survival. uPA correlated with tumor size and VEGF. VEGF was singled out in the Cox multivariate analysis as an independent predictor of survival.
When TACE is not totally effective, it may induce a significant neoangiogenetic reaction, as suggested by an increase in VEGF and b-FGF following treatment; this affects patient survival. VEGF emerges as the most reliable prognostic parameter, so it could be measured for judging TACE efficacy. Finally, antiangiogenic drugs may be indicated in TACE-treated HCC.
尽管经动脉化疗栓塞术(TACE)对肝细胞癌(HCC)有效,但它并非一种根治性治疗手段。潜在干扰其疗效的因素之一是因缺血引发的一种假设性新生血管生成反应。在我们的研究中,我们评估了接受TACE治疗的患者体内两种血管生成因子(血管内皮生长因子 [VEGF] 和碱性成纤维细胞生长因子 [b - FGF])水平的变化以及侵袭性参数之一(尿激酶型纤溶酶原激活剂 [uPA])的变化。
从71例接受TACE治疗的HCC患者身上采集三份血样:TACE治疗前(t0)、治疗后3天(t1)以及4周后进行螺旋计算机断层扫描(sCT)时(t2)。阅片放射科医生在t0时对肿瘤负荷和血管生成情况进行盲法评估,并在t2时评估残余活性。TACE作为治疗方法的选择基于美国肝病研究协会(AASLD)的指南。
27%的患者在sCT检查时达到完全缓解;平均生存期为35个月(置信区间 [CI] 31 - 40),4年生存率为57%。VEGF水平与结节数量显著相关,且在t2时无反应者中更高(P = 0.01);VEGF水平低于中位数者预测生存期更长(P = 0.008)。b - FGF与VEGF、肿瘤大小、血管生成及残余活性相关,与生存期呈临界相关性。uPA与肿瘤大小和VEGF相关。在Cox多变量分析中,VEGF被确定为生存期的独立预测因子。
当TACE并非完全有效时,如治疗后VEGF和b - FGF升高所示,它可能会引发显著的新生血管生成反应;这会影响患者生存。VEGF成为最可靠的预后参数,因此可通过检测它来判断TACE疗效。最后,抗血管生成药物可能适用于接受TACE治疗的HCC患者。