Early prediction of colorectal liver metastases treatment response with ultrasound microvessel imaging

项目总结/摘要 结直肠癌（CRC）是美国癌症死亡的第二大原因。转移 结直肠癌（mCRC），主要发生在肝脏，是CRC患者死亡的主要因素。 CRC肝转移的治疗对于mCRC患者的生存至关重要。目前，抗血管生成 该疗法在CRC肝转移的治疗中起重要作用。早期准确预测 对抗血管生成治疗的反应具有重要的临床意义，因为：1）早期识别 无应答者可以加快治疗方案的调整，以避免疾病进展， 患者免于不必要的毒性和无效治疗的医疗费用; 2）可靠的反应 评估可以帮助个体化治疗策略，优化剂量和治疗时间， 最大的治疗效果; 3）早期和准确的预测生物标志物也非常有益于 通过为临床试验提供可靠的替代终点来开发新的治疗药物。目前， 然而，临床上不存在用于抗血管生成治疗的可靠的治疗反应评估工具。 为了填补这一空白，在这里，我们提出开发一种新的超声微血管成像技术，VesselQuest， 通过定量检测肿瘤微血管来早期预测抗血管生成治疗反应， 血液动力学和形态学测量。VesselQuest可以精确测量宽动态范围的 微血管流速，并提供了空间超分辨率，不能实现目前的临床 成像方式。与其他超声技术类似，VesselQuest也是无创、安全和成本低廉的 有效VesselQuest的这些特征为结直肠肝脏的临床评估提供了极好的潜力 转移治疗对抗血管生成治疗的反应。本研究的目的1和2将集中在 VesselQuest的技术开发，为研究的目标3和4铺平了道路， 在动物肿瘤模型上验证VesselQuest，并对CRC肝脏进行初步临床研究 转移患者以评估对抗血管生成疗法的治疗反应。成功完成本 该项目将为早期预测抗血管生成治疗提供一种新颖可行的技术， CRC肝转移患者的治疗结果和生存率。为该项目开发的技术可以 也可用于评估新兴的新治疗方法，如免疫疗法。

Project Summary/Abstract Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Metastasized colorectal cancer (mCRC), primarily in liver, is the predominate factor for the mortality of CRC patients. Treatment of CRC liver metastases is essential to the survival of mCRC patients. Currently, anti-angiogenesis therapy plays a significant role in the treatment of CRC liver metastases. Early and accurate prediction of response to anti-angiogenesis therapy is of vital clinical significance because: 1) early identification of nonresponders can expedite the adjustment of treatment regimens to avoid disease progression and spare patients from unnecessary toxicity and medical expense of ineffective therapies; 2) reliable response assessment can help individualize treatment strategy and optimize dose and time course of therapy to achieve maximal treatment efficacy; 3) an early and accurate predictive biomarker is also very beneficial to development of new therapy agents by providing a reliable surrogate endpoint for clinical trials. At present, however, a reliable treatment response assessment tool for anti-angiogenesis therapy does not exist clinically. To fill this gap, here we propose to develop a novel ultrasound microvessel imaging technology, VesselQuest, to early predict anti-angiogenesis therapy response by examining tumor micro-vasculature with quantitative hemodynamic and morphologic measurements. VesselQuest can accurately measure a wide dynamic range of microvessel flow speed and offers a spatial super-resolution that cannot be achieved by current clinical imaging modalities. Similar to other ultrasound techniques, VesselQuest is also noninvasive, safe, and cost effective. These features of VesselQuest provide excellent potential for clinical assessment of colorectal liver metastases treatment response to anti-angiogenic therapy. Aims 1 and 2 of this study will be focused on technical development of VesselQuest, paving the way for the aims 3 and 4 of the study which will be focused on validating VesselQuest on an animal tumor model and conducting a pilot clinical study on CRC liver metastases patients to assess treatment response to anti-angiogenesis therapy. Successful completion of this project will provide a novel and viable technology for early prediction of anti-angiogenic therapy to improve treatment outcome and survival of CRC liver metastases patients. Technologies developed for this project can also be used for assessment of emerging novel treatment method such as immunotherapy.