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动态微泡超声造影评估靶向治疗的肿瘤反应:一项临床方案研究,入组接受抗血管生成治疗的肾癌患者的结果。

Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

机构信息

Imaging Research, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Room S6-39, Toronto, ON, Canada M4N 3M5.

出版信息

Radiology. 2011 Aug;260(2):581-90. doi: 10.1148/radiol.11101893. Epub 2011 May 9.

DOI:10.1148/radiol.11101893
PMID:21555352
Abstract

PURPOSE

To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US).

MATERIALS AND METHODS

The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected.

RESULTS

In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P < .002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days.

CONCLUSION

DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome.

摘要

目的

通过使用动态对比增强超声(DCE-US),开发并实施一种基于循证的方案,以描述肾细胞癌(RCC)对靶向治疗的血管反应。

材料与方法

本研究经机构研究伦理委员会批准,所有患者均签署书面知情同意书。2007 年 5 月至 2009 年 10 月,对 17 例转移性 RCC 患者(4 例女性,中位年龄 58 岁;范围 42-72 岁;13 例男性,中位年龄 62 岁;范围 45-81 岁)进行了 DCE-US 检查,检查时间为使用舒尼替尼治疗前和治疗后 2 周。比较了两种对比剂技术-团注和微泡破坏-再充盈输注。两种方法均测量肿瘤血流速度和部分血容量的变化,以及重复性和呼吸运动补偿的效果。通过使用实体瘤反应评估标准(RECIST)和无进展生存期(PFS),对肿瘤变化进行了计算机断层扫描评估。随后以 6 周为间隔进行随访 RECIST 测量,直至发现疾病进展。

结果

治疗后,使用破坏-再充盈输注方法测量的中位肿瘤部分血容量下降 73.2%(四分位距,46%-87%)(P<0.002),重复测量的可重复性为 9%-15%。团注法也观察到显著下降,但与输注测量相比,团注峰值(r=0.46,P=0.066)和曲线下面积(r=0.47,P=0.058)的变化相关性差。2 周内 DCE-US 参数的变化与 PFS 不相关,无法用于预测 RECIST 对最佳反应的长期评估。随访时间范围为 28-501 天,中位数为 164 天。

结论

DCE-US 可提供对血管反应的可重复性和敏感性评估,适用于多种肿瘤类型。破坏-再充盈输注方案是一种灵活的方法,但需要进一步研究以评估该方案是否可预测患者的结局。

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