Department of Imaging, Ultrasonography Unit, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.
Radiology. 2011 Jan;258(1):291-300. doi: 10.1148/radiol.10091870. Epub 2010 Oct 27.
To investigate whether there is any correlation between standard efficacy endpoints-specifically, tumor response, progression-free survival, and overall survival-and tumor perfusion parameters measured by using dynamic contrast material-enhanced ultrasonography (US) in patients with advanced hepatocellular carcinoma (HCC) treated with bevacizumab.
The institutional review board approved the study, and all patients provided written informed consent before their enrollment. Between June 3, 2005, and September 28, 2007, 42 patients (33 men, nine women; median age, 62 years; age range, 23-84 years) participated in this phase II study of single-agent bevacizumab treatment. Tumor response (based on RECIST [response evaluation criteria in solid tumors]) at 2 months was assessed in 37 patients, and progression-free survival and overall survival were assessed in all 42 patients. Dynamic contrast-enhanced US (ie, dynamic US) was performed before treatment (day 0); on days 3, 7, 14, and 60 after treatment; and every 2 months thereafter. Tumor perfusion parameters were estimated quantitatively from contrast material uptake curves constructed from raw linear data. The changes in dynamic US functional parameters between day 0 and the later time points were compared between treatment responders and nonresponders by using nonparametric tests. Given multiple comparisons, P < .001 indicated significance.
The percentage decrease in several dynamic US parameters between day 0 and day 3 showed trends toward correlation with (a) tumor response in terms of total area under the time-intensity curve (AUC) (P = .02), AUC during wash in (P = .04), AUC during washout (P = .02), and time to peak intensity (P = .03); (b) progression-free survival in terms of time to peak intensity (P = .028); and (c) overall survival in terms of AUC (P = .002) and AUC during washout (P = .003).
Dynamic US can be used to quantify dynamic changes in tumor vascularity as early as 3 days after bevacizumab administration in patients with HCC. These early changes in tumor perfusion may be predictive of tumor response at 2 months, progression-free survival, and overall survival, and they may be potential surrogate measures of the effectiveness of antiangiogenic therapy in patients with HCC.
研究在接受贝伐单抗治疗的晚期肝细胞癌（HCC）患者中，标准疗效终点（具体为肿瘤反应、无进展生存期和总生存期）与通过动态对比增强超声（US）测量的肿瘤灌注参数之间是否存在相关性。
机构审查委员会批准了该研究，所有患者在入组前均签署了书面知情同意书。在 2005 年 6 月 3 日至 2007 年 9 月 28 日期间，共有 42 例患者（33 例男性，9 例女性；中位年龄 62 岁；年龄范围 23-84 岁）参加了这项单药贝伐单抗治疗的 II 期研究。在 37 例患者中评估了 2 个月时的肿瘤反应（基于 RECIST [实体瘤反应评价标准]），在所有 42 例患者中评估了无进展生存期和总生存期。在治疗前（第 0 天）、治疗后第 3、7、14 和 60 天以及此后每 2 个月进行动态对比增强 US（即动态 US）。从原始线性数据构建的对比材料摄取曲线中定量估计肿瘤灌注参数。使用非参数检验比较治疗反应者和无反应者之间在第 0 天和稍后时间点之间的动态 US 功能参数的变化。由于进行了多次比较，因此 P <.001 表示具有统计学意义。
在第 0 天和第 3 天之间，几个动态 US 参数的百分比下降趋势与（a）总时间-强度曲线（AUC）的肿瘤反应（P =.02）、洗脱期 AUC（P =.04）、洗脱期 AUC（P =.02）和峰值强度时间（P =.03）相关；（b）无进展生存期与峰值强度时间（P =.028）相关；（c）总生存期与 AUC（P =.002）和洗脱期 AUC（P =.003）相关。
在 HCC 患者中，贝伐单抗给药后最早 3 天即可使用动态 US 定量测量肿瘤血管的动态变化。这些肿瘤灌注的早期变化可能预测 2 个月时的肿瘤反应、无进展生存期和总生存期，并且它们可能是 HCC 患者抗血管生成治疗有效性的潜在替代指标。
