Reduced Temperature Thermal Ablation for HCC and other Liver Tumors

HCC 和其他肝脏肿瘤的低温热消融

• 批准号: 8114667
• 负责人: Michael Jude Borrelli
• 金额: $ 15.77万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114667
• 关键词: Ablation; Affect; Antineoplastic Agents; Blood Vessels; Chemicals; Chemoembolization; Colon Carcinoma; Diffusion; Disease; Dose; Emulsions; Excision; Heating; Human; Incidence; Liver; Liver neoplasms; Liver parenchyma; Mediating; Modeling; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Organ Temperatures; Patients; Permeability; Pharmaceutical Preparations; Primary carcinoma of the liver cells; Probability; Procedures; Property; Quality of life; Rattus; Recurrence; Resistance; Safety; Skin; Solid; Staging; Structure; Temperature; Testing; Thermal Ablation Therapy; Time; Tissues; Treatment Efficacy; Unresectable; Viral Vector; Walkers; advanced disease; chemotherapy; cold temperature; improved; killings; liver function; liver transplantation; nanoparticle; neoplastic cell; outcome forecast; palliation; patient population; radiofrequency; research study; targeted delivery; treatment strategy; tumor

DESCRIPTION (provided by applicant): Cyclopentadecanolide (CPDL) emulsions markedly lower the threshold temperature required to thermally ablate solid tissues. The proposed study will test the hypothesis that targeted delivery of CPDL into liver tumors will preferentially sensitize them to thermal ablation at temperatures of 44-55oC and that this CPDL-mediated reduced temperature thermal ablation (CPDL-RTTA) strategy will result in safer and more effective thermal ablation of liver tumors with improved sparing of normal liver tissue. Experiments will be performed using the rat Walker 256 liver tumor model. Specific aim one is to identify the most effective means for localizing delivery of effective doses of CPDL to liver tumors and to confirm that the prescribed CPDL dose has been delivered to tumors before initiating thermal ablation. The second aim is to demonstrate that CPDL-RTTA increases tumor ablation volume, can overcome the vascular heat sink effect, and will improve the ability to establish local tumor control. If this study is successful the developed treatment strategies can be directed towards treating patients that are currently ineligible for thermal ablation therapy for their liver tumors. Thermal ablation will then have broader applicability and utility as a treatment for establishing local tumor control, downstaging liver tumors so that resection or liver transplant become treatment options, or palliating advanced disease to improve quality of life. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to develop a better procedure for thermally ablating human hepatocellular carcinoma (HCC) and other liver tumors such that tumor killing is improved while more normal tissue is spared and remains functional. This will be accomplished by targeting delivery of a chemical emulsion (active ingredient cyclopentadecanolide (CPDL)) that markedly lowers the temperature threshold required to ablate the tumor. Effective tumor ablation will be performed using temperatures between 45-55oC, which will not harm normal liver tissues since they will not have received the thermal sensitizing CPDL. If successful, the CPDL procedure will improve tumor ablation efficacy and should make tumor thermal ablation available to patients that are currently excluded because their liver tumors are too numerous and/or massive.

描述（由申请方提供）：环十五烷（CPDL）乳剂可显著降低热消融实体组织所需的阈值温度。该拟议研究将测试以下假设：将CPDL靶向递送到肝肿瘤中将优先使它们对44- 55 ℃温度下的热消融敏感，并且这种CPDL介导的降低温度热消融（CPDL-RTTA）策略将导致更安全和更有效的肝肿瘤热消融，同时改善正常肝组织的保留。实验将使用大鼠步行者256肝肿瘤模型进行。具体目标之一是确定将有效剂量的CPDL局部递送到肝肿瘤的最有效方法，并确认在开始热消融之前已将规定的CPDL剂量递送到肿瘤。第二个目的是证明CPDL-RTTA增加肿瘤消融体积，可以克服血管散热效应，并将提高建立局部肿瘤控制的能力。如果这项研究是成功的，所开发的治疗策略可以针对治疗目前不适合热消融治疗肝肿瘤的患者。然后，热消融将具有更广泛的适用性和实用性，作为建立局部肿瘤控制的治疗方法，降低肝脏肿瘤的分期，使切除或肝脏移植成为治疗选择，或缓解晚期疾病以改善生活质量。 公共卫生关系：该提案的目的是开发一种更好的用于热消融人肝细胞癌（HCC）和其他肝脏肿瘤的程序，使得肿瘤杀伤得到改善，同时更多的正常组织得以保留并保持功能。这将通过靶向递送化学乳剂（活性成分环十五烷（CPDL））来实现，该乳剂显著降低消融肿瘤所需的温度阈值。将使用45- 55 ℃之间的温度进行有效的肿瘤消融，这不会伤害正常的肝组织，因为它们不会接受热敏CPDL。如果成功，CPDL手术将提高肿瘤消融疗效，并应使肿瘤热消融术适用于目前因肝脏肿瘤太多和/或太大而被排除在外的患者。