Monitoring neoadjuvant chemotherapy of breast cancer using 3D subharmonic aided pressure estimation

项目摘要 新辅助化疗(NAC)是治疗局部晚期乳腺癌的标准护理 (LABC)。手术前应用这一系统治疗使患者受益，提高了患者的 保乳手术，化疗反应的早期指征，以及改善的预后 高危患者的某些亚群。对NAC的临床反应与病理结果相关 手术时及术后存活情况。此外，在早期确定无响应者也很重要 疗程，以避免不必要的费用和无效治疗的副作用，例如 恶心、脱发、血液毒性、神经毒性(如紫杉烷)或心脏毒性(如蒽环类药物)。它 也有报道称，对初始新辅助方案没有反应，但有反应的患者的存活率 对不同的第二种新辅助方案的反应类似于最初方案的应答者的存活率。因此， 早期评估乳腺癌对NAC的反应可以通过允许更早的治疗来提高患者的生存率 修改，并有可能加快有效管理NAC的时间表。最大的 监测NAC的挑战是在治疗的早期阶段量化反应。响应评估 目前依赖于肿瘤的缩小，但肿瘤的大小变化，即形态变化，可以晚于 功能和生理变化。因此，需要探索新的功能评估，以改善 早期治疗反应预测的准确性。间质流体压力(IFP)已被认为是一个因素 影响治疗反应的。IFP的增加阻碍了治疗剂的有效摄取，并减少了 癌症治疗的疗效。乳腺肿瘤的IFP可以直接用芯子有创地测量-- 针灸技术。然而，这种侵入性方法很难在患者身上应用，也不是标准的护理。我们的 研究小组提出了一种名为次谐波辅助压力估计(SHAPE)的创新超声技术 用于非侵入性IFP评估，最近进行了一项3D SHAPE监测治疗能力的试点研究 接受NAC治疗的妇女的反应。这项研究表明，亚谐信号在肿瘤中的差异 相对于正常组织来说，最早可以预测治疗反应的只有10%的药物 治疗方案(即1个NAC周期)。虽然令人鼓舞，但这项研究是基于有限数量的案例 在一家机构。在这个项目中，我们建议将学术界和工业界的研究人员聚集在一起 以便进行多中心临床评估，以验证先前的发现。我们的假设是 肿瘤相对正常组织的亚谐信号差异可预测乳腺癌NAC反应 在10%的治疗方案后。

Project Abstract Neoadjuvant chemotherapy (NAC) is the standard of care for treatment of locally advanced breast cancer (LABC). Application of this systematic therapy before surgery benefits patients by providing improved rates of breast-conserving surgery, early indication of response to chemotherapy, as well as improved outcomes for certain subgroups of high-risk patients. The clinical response to NAC is correlated with the pathologic outcome at the time of surgery and post-surgery survival. Also, it is important to identify non-responders early in the course of treatment to save them from unnecessary cost and side effects of ineffective treatment, such as nausea, alopecia, haematological toxicity, neurotoxicity (e.g. taxanes) or cardiotoxicity (e.g. anthracyclines). It has also been reported that survival of patients not responding to an initial neoadjuvant regimen, but responding to a different second neoadjuvant regimen is similar to the survival of responders to the initial regimen. Thus, early assessment of breast cancer response to NAC can improve patients' survival by allowing for earlier therapy modification, and potentially accelerating the timeline to administration of an effective NAC. The biggest challenge in monitoring NAC is to quantify response at an early stage of therapy. Response assessment currently relies on tumor shrinkage, but the tumor size changes, i.e. morphologic changes, can happen later than functional and physiologic changes. Thus, new functional assessments need to be explored to improve the accuracy of early therapy response prediction. Interstitial fluid pressure (IFP) has been suggested as a factor affecting therapeutic response. Increased IFP prevents an effective uptake of therapeutic agents and reduces the efficacy of cancer therapy. The IFP of breast tumors can be directly measured invasively using a wick-in- needle technique. However, this invasive method is difficult to apply in patients and not standard of care. Our group has proposed an innovative ultrasound technique called subharmonic-aided pressure estimation (SHAPE) for noninvasive IFP evaluation and recently conducted a pilot study of 3D SHAPE's ability to monitor treatment response in women undergoing NAC. This study showed that the subharmonic signal difference in the tumor relative to the normal tissue could predict treatment response as early as after administration of only 10% of therapy regimen (i.e., 1 cycle of NAC). While encouraging, this study was based on a limited number of cases at a single institution. In this project we propose to bring together researchers from academia and industry in order to conduct a multi-center clinical evaluation to validate previous findings. Our hypothesis is that the subharmonic signal difference in the tumor relative to the normal tissue can predict breast cancer NAC response after 10% of therapy regimen.