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

• 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
• 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

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.

项目总结/摘要 据估计，美国每年有34，000名患者被诊断患有原发性肝脏， 许多患者将从广泛的原发性肿瘤部位发生肝转移。可惜 绝大多数患者不适合手术切除，手术切除是唯一可靠的治愈方法。 治疗肝肿瘤，患者的五年生存率约为10 - 20%。 原发性疾病。主要的临床挑战是大多数肿瘤形成于器官深处，靠近主要器官。 使手术切除复杂化且禁忌其他一线治疗的血管、胆管或神经 治疗。相控电疗法是一种新型的微创治疗技术 由Gradient Medical开发，用于治疗无法手术的肿瘤， 电脉冲使细胞膜不稳定并诱导坏死和凋亡的可调组合 细胞死亡在本提案中，我们研究了这种方法治疗肝脏肿瘤的可行性， 两个具体目的：1）用ACE方案表征选择性靶向。2)多阶段开发 交变极性脉冲发生系统。在拟议的研究中，Gradient Medical将设计并构建一个 新颖的脉冲发生系统，能够在多达四个脉冲之间瞬时输送电能， 同步的温度传感施加器。这种方法的可行性将通过使用 台式灌注肝脏模型，其能够直接可视化由非 热脉冲电场介导的细胞死亡机制。初步安全性和体内疗效将在 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 针对兽医患者的自发性肝肿瘤。