INTRAOPERATIVE RADIATION THERAPY AND HYPERTHERMIA

术中放射治疗和热疗

• 批准号: 3192068
• 负责人: THOMAS ANTHONY COLACCHIO
• 金额: $ 34.94万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3192068
• 关键词: carcinoma; clinical biomedical equipment; colon neoplasms; combination cancer therapy; dogs; electrophysiology; neoplasm /cancer diagnosis; neoplasm /cancer radiation therapy; neoplasm /cancer surgery; neoplasm /cancer thermotherapy; pancreatic islet neoplasm; radiation dosage; radiobiology; ultrasound

The objective of this study is to evaluate the use of intraoperative hyperthermia (IOHT) in combination with intraoperative radiation therapy (IORT) for the treatment of locally unresectable or recurrent pancreatic and colorectal carcinomas. There are three components of the study which are necessary to meet this objective. First, our experience with single element ultrasound transducers in heating large, complexly shaped and deep seated tumors has emphasized the need for the development of a hyperthermia system with multiple element flexible transducers with the power to each element under computer control. Thus, we plan to develop a flexible, multi-element ultrasound transducer hyperthermia system with adequate thermometry to allow computer monitored individual element power control. Second, normal tissues are tolerant to temperatures up to 42degrees- 44degreesC for relatively long periods of time depending on the tissue type. However, thermal enhancement ratios have not been established to evaluate the effect of combining large single doses of radiation with hyperthermia on many normal tissues including peripheral nerves. Since the intraoperative use of radiation with hyperthermia allows for the retrac- tion, resection, bypass or defunctionalization of nearly all significant normal structures except for peripheral nerves without unacceptable morbidity, a knowledge of the tolerance of peripheral nerves to these forms of therapy is essential to aid in the assessment of potential risks and benefits in human clinical trials. Thus, a second component of the study will be performed in dogs to evaluate the tolerance of peripheral nerves to IORT and IOHT, both alone and in combination. Thirdly, approximately 18 months after the start of the grant, when the first prototype multi-element transducers are available and preliminary data from the nerve studies has been obtained, we will initiate a Phase 1 trial of combination IORT and IOHT therapy utilizing the individual element power controlled multi- element transducer in patients with unresectable or recurrent pancreatic and colorectal carcinomas. We plan to treat these tumors with 1500 to 1750 cGy IORT and IOHT treatments of 43degreesC or greater for 60 minutes. This Phase 1 trial will evaluate the performance of the new multi-element transducer system and the feasibility and toxicity of this combined therapy along with accrual capability, techniques for determining therapeutic efficacy and stratification in preparation for a Phase 2 trial of local tumor control that will combine IORT with IOHT at varying thermal doses. The engineering development and clinical trial components of this study will be performed at the Darthmouth-Hitchcock Medical Center, and the animal peripheral nerve tolerance component will be performed at the Colorado State University Veterinary Teaching Hospital.

本研究的目的是评价术中 高温（IOHT）联合术中放疗 （IORT）用于治疗局部不可切除或复发性胰腺癌 和结肠直肠癌。 这项研究有三个组成部分， 是实现这一目标所必需的。 首先，我们的经验与单一 元件超声换能器加热大，形状复杂，深 肿瘤的热疗强调了发展热疗的必要性， 具有多个元件柔性换能器的系统，每个换能器具有电源 在计算机控制下。 因此，我们计划开发一个灵活的， 多元件超声换能器热疗系统， 温度测量允许计算机监控的单个元件功率控制。 第二，正常组织可以耐受高达42度的温度- 44 ℃下持续相对较长的时间，具体取决于组织 类型. 然而，热增强比尚未建立， 评估大剂量单次辐射与 高温对包括周围神经在内的许多正常组织的影响。 以来 术中使用放射和热疗允许回撤， 切除，旁路或去功能化几乎所有重要的 正常结构，除了周围神经，没有不可接受的 发病率，外周神经对这些形式的耐受性的知识 对于帮助评估潜在风险和 在人体临床试验中的益处。 因此，研究的第二个组成部分 将在犬中进行，以评价外周神经对 IORT和IOHT，单独和组合。 第三，约18 月后开始的赠款，当第一个原型多元素 传感器可用，神经研究的初步数据 我们将启动一项联合IORT和 IOHT疗法利用单个元件功率控制的多个 元件换能器在不可切除或复发性胰腺癌患者中的应用 和结肠直肠癌。 我们计划用1500到1750 cGy IORT和IOHT处理，43 ℃或更高，持续60分钟。 这 1期试验将评估新的多元素的性能 传感器系统和这种联合治疗的可行性和毒性 沿着累积能力，用于确定治疗的技术 在准备2期试验中的疗效和分层， 将联合收割机IORT与IOHT以不同的热剂量组合的肿瘤控制。 本研究的工程开发和临床试验部分 将在达特茅斯-希区柯克医疗中心进行， 动物外周神经耐受部分将在 科罗拉多州立大学兽医教学医院。