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: 10614640
• 负责人: Kibo Nam
• 金额: $ 44.56万
• 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/10614640
• 关键词: 3-Dimensional; Academia; Acceleration; Accounting; Acoustics; Adjuvant Chemotherapy; Affect; Alopecia; Anthracycline; Biological Markers; Breast Cancer Patient; Breast Cancer therapy; Breast-Conserving Surgery; Cardiotoxicity; Clinical; Clinical Research; Computer software; Diagnosis; Diameter; Early treatment; Environment; Evaluation; Frequencies; Hematology; Industry; Institution; Intercellular Fluid; Local Therapy; 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; Toxic effect; Tumor Volume; Woman; advanced breast cancer; breast imaging; cancer subtypes; cancer therapy; chemotherapy; 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; timeline; 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标准治疗 （实验室检查）。手术前应用这种系统疗法可以提高患者的手术成功率，从而使患者受益。 保乳手术、化疗反应的早期迹象以及改善的结果 高危患者的某些亚组。 NAC 的临床反应与病理结果相关 手术时和术后生存率。此外，尽早识别无反应者也很重要 治疗过程，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（例如紫杉烷类）或心脏毒性（例如蒽环类药物）。它 也有报道称，对初始新辅助治疗方案没有反应但有反应的患者的存活率 不同的第二新辅助治疗方案与初始治疗方案的反应者的生存率相似。因此， 早期评估乳腺癌对 NAC 的反应可以通过早期治疗来提高患者的生存率 修改，并有可能加快有效 NAC 管理的时间表。最大的 监测 NAC 的挑战是量化治疗早期阶段的反应。反应评估 目前依赖于肿瘤缩小，但肿瘤大小的变化，即形态变化，可能会晚于 功能和生理变化。因此，需要探索新的功能评估来改善 早期治疗反应预测的准确性。间质液压力（IFP）被建议作为一个因素 影响治疗反应。增加的 IFP 会阻碍治疗药物的有效吸收并减少 癌症治疗的功效。乳腺肿瘤的 IFP 可以使用灯芯直接侵入式测量。 针技术。然而，这种侵入性方法很难应用于患者并且不是标准护理。我们的 研究小组提出了一种创新的超声技术，称为次谐波辅助压力估计（SHAPE） 用于无创 IFP 评估，并最近对 3D SHAPE 监测治疗的能力进行了初步研究 接受 NAC 的女性的反应。这项研究表明，肿瘤中的次谐波信号差异 相对于正常组织，早在仅施用 10% 的药物后就可以预测治疗反应 治疗方案（即 1 个周期的 NAC）。虽然令人鼓舞，但这项研究是基于有限的案例 在一个机构。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 为了进行多中心临床评估以验证先前的研究结果。我们的假设是 肿瘤相对于正常组织的次谐波信号差异可以预测乳腺癌 NAC 反应 10%的治疗方案后。