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

项目摘要/摘要 据估计，美国每年有3.4万名患者被诊断为原发性肝病，患者的肝脏面积明显大于 许多患者将从广泛的原发肿瘤部位发展为肝转移。不幸的是， 这些患者中的绝大多数不适合手术切除，而手术切除是唯一可靠的治疗方法。 治疗肝脏肿瘤，患者的五年存活率约为10%至20% 患有原发病。临床上的主要挑战是大多数肿瘤形成于器官深处，靠近大脑皮层。 血管、胆管或神经，使手术切除变得复杂，并禁止其他第一线 治疗。阶段性算法控制电疗(PACE)是一种新的微创治疗技术 梯度医疗公司开发的超短高强度治疗不能手术的肿瘤 电脉冲破坏细胞膜的稳定性并诱导可调的坏死和凋亡的组合 细胞死亡。在这项建议中，我们探讨这种方法治疗肝肿瘤的可行性。 两个具体目标：1)表征使用ACE协议的选择性靶向。2)多阶段的发展 交变极性脉冲发生系统。在拟议的研究中，梯度医疗将设计和建造一个 一种新颖的脉冲产生系统，能够在多达四个脉冲之间实现瞬时电能传输 同步温度传感涂布器。此方法的可行性将使用 台式灌流肝脏模型，允许直接可视化由非 热脉冲电场介导的细胞死亡机制。初步的安全性和体内疗效将是 在活体大动物肝脏模型中进行了评估。这项可行性研究的结果将用于生成 体内第二阶段安全性和有效性研究所需的初步治疗计划算法 抗自发性肝肿瘤的兽医患者。

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.