Feasibility of a Multi-Phase Algorithmic Non-Thermal Ablation Technology for the Treatment of Inoperable Tumors

多阶段算法非热消融技术治疗无法手术肿瘤的可行性

基本信息

批准号：
10547371
负责人：
Jordan Fong
金额：
$ 25.95万
依托单位：
GRADIENT MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-16 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10547371
关键词：
3-Dimensional Ablation Algorithms Animals Apoptotic Appointment Automobile Driving Benign Biomedical Engineering Blood Vessels Cancer Etiology Cell Death Cell Nucleus Cell membrane Cells Cellular Morphology Characteristics Charge Chemotherapy and/or radiation Clinical Comprehensive Cancer Center Computer Models Cryosurgery Custom Cytoplasm Data Deposition Development Diagnosis Disease Dose Electric Stimulation Therapy Electrodes Electronics Electroporation Environment Excision Feasibility Studies Feedback Focused Ultrasound Therapy Generations Geometry Goals Institution Interdisciplinary Study Intervention Joints Life Liver Liver neoplasms Malignant - descriptor Malignant Neoplasms Malignant neoplasm of liver Manuals Mediating Medical Membrane Metastatic Neoplasm to the Liver Metastatic to Modality Modeling Morphology Necrosis Nerve Operative Surgical Procedures Organ Pathologist Patients Phase Physiologic pulse Population Positioning Attribute Primary Neoplasm Prognosis Protocols documentation Public Health Radiation therapy Radiofrequency Interstitial Ablation Reproducibility Research Personnel Resectable Safety Site Solid Solid Neoplasm Source Structure Surgical Oncologist Survival Rate System Techniques Technology Temperature Temperature Sense Testing Thermal Ablation Therapy Time Tissues Toxic effect Treatment Protocols Unresectable Visualization Work base bile duct cancer cell cancer therapy chemotherapy curative treatments design efficacy study electric field electrical property flexibility gastrointestinal high resolution imaging imaging approach in vivo innovation instrumentation medical schools microwave ablation millisecond minimally invasive mortality neoplastic cell novel pancreatic neoplasm pre-clinical preservation response safety study standard care survival outcome treatment optimization treatment planning tumor tumor ablation voltage

项目摘要

Project Summary / Abstract An estimated 34,000 patients are diagnosed in the US with primary liver each year with a substantially larger number of patients will developing liver metastasis from a broad range of primary tumor sites. Unfortunately, the vast majority of these patients are not candidates for surgical resection, which is the only reliably curative treatment for liver tumors, yielding a five year survival rate of approximately between 10 and 20% for patients with primary disease. The primary clinical challenge is that most tumors form deep within organs, near major blood vessels, bile ducts, or nerves which complicate surgical removal and contraindicate other first line treatments. Phased Algorithmically Controlled Electrotherapy (PACE) is a new minimally invasive technique developed by the Gradient Medical for the treatment of inoperable tumors which uses ultrashort high intensity electrical pulses to destabilize the cell membrane and induce a tunable combination of necrotic and apoptotic cell death. In this proposal we investigate the feasibility of this approach for the treatment of liver tumors through two specific aims: 1) Characterization of Selective Targeting with ACE protocols. 2) Development of a Multiphase Alternating Polarity Pulse Generation System. In the proposed study Gradient Medical will design and build a novel pulse generation system which enables instantaneous electrical energy delivery between up to four synchronized temperature sensing applicators. Feasibility of this approach will be demonstrated using a benchtop perfused liver model which enables direct visualization of the treatment zones created by the non- thermal pulsed electric field mediated cell death mechanisms. Preliminary safety and in vivo efficacy will be evaluated in an in vivo large animal liver model. The results from this feasibility study will be used to generate preliminary treatment planning algorithms necessary for subsequent Phase II in vivo safety and efficacy studies against spontaneous liver tumors in veterinary patients.

项目摘要 /摘要估计每年在美国诊断出34,000名患者患有原发性肝脏的患者，其较大的患者数量将从广泛的原发性肿瘤部位发展肝转移。不幸的是，这些患者中的绝大多数不是手术切除的候选者，这是唯一可靠的治疗方法肝肿瘤的治疗，患者的生存率约为10％至20％原发性疾病。主要的临床挑战是，大多数肿瘤在器官内部深处形成，附近血管，胆管或神经使手术清除复杂并禁忌其他第一线治疗。分阶段算法控制电疗（PACE）是一种新的微创技术由梯度医疗开发用于治疗使用超短强度的无法操作的肿瘤电脉冲可破坏细胞膜并诱导坏死和凋亡的可调组合细胞死亡。在此提案中，我们调查了这种方法通过两个具体的目的：1）用ACE协议对选择性定位的表征。 2）开发多相交替的极性脉冲产生系统。在拟议的研究中，渐变医疗将设计和建造新型脉搏生成系统，可实现多达四个的瞬时电能输送同步温度传感涂抹器。这种方法的可行性将使用台式灌注肝模型，可直接可视化非 - 热脉冲电场介导的细胞死亡机制。初步安全性和体内功效将是在体内大动物肝模型中进行评估。可行性研究的结果将用于生成随后的II期体内安全性和有效性研究所需的初步治疗计划算法针对兽医患者的自发肝肿瘤。