Breast Cancer Stage I, Fibroadenoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREHarmonic motion imaging guided focused ultrasound (HMIgFUS)
Harmonic motion imaging guided focused ultrasound (HMIgFUS) is a combined treatment and imaging method, in which focused ultrasound (FUS) is used to thermally ablate tissue and harmonic motion imaging (HMI) is used for FUS guidance and monitoring. FUS applies high intensity focused ultrasound waves at its specified target to heat the tissue over a specified duration, causing cell death at the target area. HMI is an elasticity imaging technique which induces dynamic tissue vibrations at the target for tissue elasticity characterization. One of the inclusion criteria for this study is that participants must be scheduled for surgical excision of their breast tumor. In this study, HMIgFUS will be applied to anesthetized participants immediately prior to their scheduled surgery. HMI imaging will also be performed immediately prior to and after HMIgFUS application.
PROCEDUREMicrobubble-mediated Low Intensity Focused Ultrasound (LIFU)
Microbubble-mediated Low Intensity Focused Ultrasound (LIFU) is a minimally invasive procedure which delivers localized ultrasound energy to the target region, causing cavitation of microbubbles to safely and transiently increase the permeability of vessels that aids local delivery of medicine.
DRUGMicrobubbles
Definity is a diagnostic ultrasound enhancing agent used to improve the clarity of echocardiograms and other ultrasound images. It consists of tiny, gas-filled lipid microspheres (about the size of a red blood cell) that circulate in the bloodstream to reflect ultrasound waves.
Sponsors
Columbia University
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with ablation | 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 depth | 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 | 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. |
| R2 value of ablated lesion area | 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. |
Countries
United States
Contacts
CONTACTShiqi Hu, MSc
PRINCIPAL_INVESTIGATORBret Taback, MD
Columbia University
Outcome results
None listed