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.

项目概要/摘要据估计，美国每年有 34,000 名患者被诊断出患有原发性肝脏疾病，其中规模更大许多患者会从广泛的原发肿瘤部位发生肝转移。不幸的是，这些患者中的绝大多数不适合手术切除，这是唯一可靠的治愈方法治疗肝肿瘤，患者五年生存率约为 10% 至 20% 伴有原发病。主要的临床挑战是大多数肿瘤形成于器官深处，靠近主要部位。血管、胆管或神经使手术切除变得复杂并且不适合其他一线治疗治疗。相控算法控制电疗 (PACE) 是一种新型微创技术由 Gradient Medical 开发，用于治疗无法手术的肿瘤，使用超短高强度电脉冲破坏细胞膜的稳定性并诱导坏死和凋亡的可调组合细胞死亡。在本提案中，我们通过以下方式研究了这种方法治疗肝肿瘤的可行性两个具体目标：1）使用 ACE 协议表征选择性靶向。 2) 多相的开发交替极性脉冲发生系统。在拟议的研究中，梯度医疗将设计和建造一个新颖的脉冲发生系统，可在多达四个之间实现瞬时电能传输同步温度传感涂抹器。该方法的可行性将通过台式灌注肝脏模型，可以直接可视化由非肝脏创建的治疗区域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在体内大型动物肝脏模型中进行评估。该可行性研究的结果将用于生成后续 II 期体内安全性和有效性研究所需的初步治疗计划算法对抗兽医患者的自发性肝肿瘤。