Medical Imaging and Focused Ultrasound Treatment for Breast Tumors Using Harmonic Motion Imaging (HMI)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Number of patients with ablation
研究概览
简要总结
This study will investigate Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) method for ablation and sonoporation monitoring of breast tumors. The aim of this study is to evaluate the efficacy of real-time guidance/monitoring and ablation/sonoporation method. The hypothesis behind this proposed study is that High Intensity Focused Ultrasound (HIFU) can be used to ablate tumor tissue, and microbubble-mediated Low Intensity Focused Ultrasound (LIFU) can be used to sonoporate tumor vasculature. The investigators of this study also hypothesize that HMI can be used to monitor HIFU ablation by measuring the changes in tissue stiffness that occur as a result of thermal ablation, guide LIFU sonoporation and HIFU ablation targeting stiff tumor tissue, and the HMI-monitored stiffness changes during ablation will correlate with post-treatment immune response. The ultimate goals of this study are: first, to assess whether these techniques can be used in the clinic in order to provide a well-monitored, noninvasive tumor ablation/sonoporation method for benign tumors and breast cancers, to minimize side effects due to invasiveness and enhance therapeutic effects of current methods; second, to make full use of the real-time monitoring capability of HMIgFUS for more precise, point-of-care treatment planning to ensure success of ablation/sonoporation and immune activation.
详细描述
The objectives of this study are to demonstrate the initial clinical feasibility of using Harmonic Motion Imaging (HMI) for guiding and monitoring 1) Focused Ultrasound Surgery (FUS) in patients with benign tumors and stage 1 non-metastatic breast cancers and 2) microbubble-mediated Low Intensity Focused Ultrasound (LIFU), i.e., sonoporation, in early-stage, non-metastatic breast cancer patients. The secondary objective is to investigate the correlation between HMI-informed treatment response with patients' post-treatment immune profile.
FUS is a non-invasive, non-ionizing treatment procedure that precisely focuses and delivers a large amount of ultrasound energy to the target area, causing a localized temperature rise and cell necrosis at the target. Patients with small solid tumors without positive lymph nodes have the highest survival rate. However, especially for patients with benign tumors (most common in younger women) and older patients (>65 years old) who fit these criteria, an alternative treatment technique that is far less invasive than the current surgical or invasive ablative intervention may be more beneficial. The main advantage of treating breast tumors with focused ultrasound ablation (FUS) is its noninvasiveness, i.e., no need for surgery. Without surgery, recovery from the procedure is much faster, patients may experience less pain, and cosmetic results may be improved.
On the other hand, microbubbles have been approved for use by the FDA in contrast-enhanced ultrasound imaging, e.g., cardiac and liver imaging. Research has shown that microbubble mediated LIFU can improve intratumoral drug uptake via a phenomenon termed sonoporation, as a result of cavitation of microbubbles. Sonoporation does not cause any unexpected bias or additional toxicity compared with chemotherapy alone. Currently, sonoporation lacks imaging guidance. In this study, HMI and contrast-enhanced power Doppler will be investigated to guide and monitor sonoporation. Microbubbles will be injected at an FDA-approved dose and route.
HMI is an ultrasound elasticity method that can provide measurements of the locally generated mechanical response and inherent mechanical properties of tissues. The result is a new image that contains unique localized information on the relative stiffness in and around the tumor. HMI can be performed simultaneously with HIFU ablation so that HIFU ablation can be monitored with HMI without interruption of HIFU treatment. When used for monitoring thermal ablation using FUS, the integrated system is referred to as HMIgFUS, which stands for Harmonic Motion Imaging for Focused Ultrasound. The resulting synchronous monitoring system has the ability to follow and identify the areas of necrosis. This study aims to evaluate the HMI technique for monitoring FUS ablation in a clinical setting and investigate the correlation between HMI-monitored displacement and patients' immune response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Focused Ultrasound Surgery
- •Inclusion criteria:
- •Women age 18 years or older with benign tumors or early-stage, non-metastatic breast cancer (stage I without the involvement of axillary lymph nodes)
- •Scheduled to receive surgical resection of the tumor by their clinical care team
排除标准
- •Patients who have received or are scheduled to receive thermal ablation or treatment of the tumor as part of their clinical care
- •Pregnant or lactating
- •Presence of breast implants
- •Have a history of laser or radiation therapy to the targeted breast.
- •Microbubble-mediated LIFU, i.e., sonoporation
- •Inclusion criteria:
- •Women 18 years or older
- •Deemed eligible to receive neoadjuvant systemic therapy as per the treating physician, with the dose and schedule deemed appropriate by the treating physician
- •Any stage invasive breast cancer provided the primary breast tumor size is at least 4 mm
- •Exclusion criteria:
- •Pregnant or lactating
- •Presence of breast implants
- •History of laser or radiation therapy to the affected breast
- •Contraindication history or hypersensitivity to ultrasound contrast agents, e.g., Definity, including polyethylene glycol (PEG) allergy.
研究组 & 干预措施
HMIgFUS
Each study participants' tumors will be imaged using Harmonic Motion Imaging (HMI), an ultrasound elastography method. A central portion of the tumor will then be ablated and monitored using Harmonic Motion Imaging guided Focus Ultrasound (HMIgFUS). Only one portion of the tumor will be ablated; the other portions of the tumor, including tumor margins, will not be ablated. Following ablation, the tumor will be imaged again using HMI.
干预措施: Harmonic motion imaging guided focused ultrasound (HMIgFUS) (Procedure)
HMIgLIFU
Eligible participants have early-stage breast cancers and are scheduled to receive neoadjuvant chemotherapy as part of their clinical care. On the day of chemotherapy infusion, elasticity images of the lesions and surrounding tissues will be collected using HMI before infusion after tumor identification on ultrasound imaging. Within an hour after infusion, the participants' tumors will be treated with microbubble-mediated Low-Intensity Focused Ultrasound (LIFU), i.e. sonoporation.
干预措施: Microbubble-mediated Low Intensity Focused Ultrasound (LIFU) (Procedure)
HMIgLIFU
Eligible participants have early-stage breast cancers and are scheduled to receive neoadjuvant chemotherapy as part of their clinical care. On the day of chemotherapy infusion, elasticity images of the lesions and surrounding tissues will be collected using HMI before infusion after tumor identification on ultrasound imaging. Within an hour after infusion, the participants' tumors will be treated with microbubble-mediated Low-Intensity Focused Ultrasound (LIFU), i.e. sonoporation.
干预措施: Microbubbles (Drug)
结局指标
主要结局
Number of patients with ablation
时间窗: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
To identify markers of ablation progression using HMIgFUS images, thereby predicting whether ablation occurred or not. The investigators will also use differences in HMI imaging performed before and after ablation to assess the presence of ablation. The results from both of these methods will be validated with pathological findings, to determine whether ablation was achieved.
R2 value of ablated lesion area
时间窗: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
The area of the lesion (in mm\^2) as shown on HMIgFUS images will be compared and validated with pathological findings.
R2 value of ablated lesion depth
时间窗: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
The depth of the lesion (in mm away from the surface of the skin) as shown on HMIgFUS images will be compared and validated with pathological findings.
R2 value of ablated lesion width
时间窗: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
The width of the lesion (in mm laterally across the lesion) as shown on HMIgFUS images will be compared and validated with pathological findings.
次要结局
未报告次要终点
研究者
Bret Taback
Assistant Professor of Surgery
Columbia University