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

使用 3D 分谐波辅助压力估计监测乳腺癌新辅助化疗

• 批准号: 10406360
• 负责人: Kibo Nam
• 金额: $ 43.18万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406360
• 关键词: 3-Dimensional; Academia; Accounting; Acoustics; Affect; Alopecia; Anthracycline; Biological Markers; Breast Cancer Patient; Breast-Conserving Surgery; Caliber; Cardiotoxicity; Clinical; Clinical Research; Computer software; Diagnosis; Early treatment; Environment; Evaluation; Frequencies; Hematology; Industry; Institution; Intercellular Fluid; Mammary Neoplasms; Measurement; Measures; Methods; Microbubbles; Modification; Monitor; Morphology; Nausea; Needles; Needs Assessment; Neoadjuvant Therapy; Normal tissue morphology; Operative Surgical Procedures; Outcome; Pathologic; Patients; Physiological; Pilot Projects; Prediction of Response to Therapy; Regimen; Reporting; Research Personnel; Signal Transduction; Subgroup; System; Techniques; Technology; Testing; Therapeutic Agents; Time; TimeLine; Toxic effect; Tumor Volume; Woman; advanced breast cancer; base; breast imaging; cancer subtypes; cancer therapy; chemotherapy; clinical center; contrast enhanced; cost; high risk; improved; improved outcome; ineffective therapies; innovation; malignant breast neoplasm; neurotoxicity; novel; novel marker; predicting response; pressure; pressure sensor; prevent; research clinical testing; response; screening; side effect; standard of care; taxane; treatment response; tumor; ultrasound; uptake

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.

项目摘要 新辅助化疗（NAC）是治疗局部晚期乳腺癌的护理标准 （LABC）。通过提供提高的率 乳腺癌手术，早期表明对化学疗法的反应以及改善的结果 高危患者的某些亚组。对NAC的临床反应与病理结局相关 在手术和手术后生存时。此外，重要的是在早期识别非反应者 治疗过程以使他们免于不必要的成本和无效治疗的副作用，例如 恶心，脱发，血液学毒性，神经毒性（例如紫杉烷）或心脏毒性（例如蒽环类药物）。它 还据报道，对初始新辅助方案不反应的患者的存活率，但反应 对于不同的第二新辅助方案，与初始方案的响应者的存活相似。因此， 乳腺癌对NAC的反应的早期评估可以通过允许早期治疗来改善患者的生存率 修改，并有可能加速时间表有效的NAC。最大 监测NAC的挑战是在治疗的早期阶段量化反应。响应评估 目前依赖肿瘤收缩 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。已建议将间质流体压力（IFP）作为一个因素 影响治疗反应。增加IFP可防止有效摄取治疗剂并减少 癌症治疗的功效。乳腺肿瘤的IFP可以直接使用oo侵入性测量 针技术。但是，这种侵入性方法难以在患者而不是标准护理中应用。我们的 小组提出了一种创新的超声技术，称为亚锤子辅助压力估计（Shape） 对于非侵入性IFP评估，最近对3D形状监测治疗的能力进行了试点研究 接受NAC的妇女的反应。这项研究表明肿瘤的亚谐波信号差 相对于正常组织，只要在给药后，就可以预测治疗反应 治疗方案（即NAC的1个周期）。在鼓励的同时，这项研究是基于数量有限的案例 在一个机构。在这个项目中，我们建议将来自学术界和行业的研究人员聚集在一起 为了进行多中心临床评估以验证先前的发现。我们的假设是 肿瘤相对于正常组织的亚谐波信号差异可以预测乳腺癌NAC反应 经过10％的治疗方案。