INTRAOPERATIVE RADIATION THERAPY AND HYPERTHERMIA

术中放射治疗和热疗

• 批准号: 3192066
• 负责人: THOMAS ANTHONY COLACCHIO
• 金额: $ 39.2万
• 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/3192066
• 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.

本研究的目的是评估术中血管内固定器的使用。 高温(IOHT)联合术中放射治疗 (IORT)治疗局部不能切除或复发的胰腺 和结直肠癌。这项研究有三个组成部分， 是实现这一目标所必需的。首先，我们对单身的体验 用于大型、复杂形状和深部加热的元件超声换能器 坐位肿瘤强调了发展热疗的必要性。 具有多元件柔性换能器的系统，每个换能器都有电源 在计算机控制下的元素。因此，我们计划开发一种灵活的、 一种多元件超声换能器热疗系统 温度测量，允许计算机监控单个元件的电源控制。 其次，正常组织可以耐受高达42度的温度-- 44摄氏度，根据组织的不同，持续相对较长的时间 打字。然而，热增强率尚未确定为 评估大剂量单次照射联合应用的效果 包括周围神经在内的许多正常组织的体温升高。自.以来 术中应用放射治疗配合热疗可使术后复查- 切除、切除、搭桥或去功能化几乎所有重要的 除周围神经外的正常结构无不可接受 发病率，即周围神经对这些形式的耐受性的知识 治疗对帮助评估潜在风险和 在人体临床试验中的益处。因此，这项研究的第二部分 将在狗身上进行，以评估周围神经对 IORT和IOHT，单独和联合使用。第三，大约18 在拨款开始的几个月后，当第一个原型多元素 传感器是可用的，来自神经研究的初步数据已经 ，我们将启动IORT和联合IORT的第一阶段试验 利用单元件功率控制的多通道IOHT治疗 元素换能器在不能切除或复发胰腺患者中的应用 和结直肠癌。我们计划用1500到1750人来治疗这些肿瘤 43℃或以上的Cgy IORT和IOHT处理60分钟。这 第一阶段试验将评估新的多元素的性能 换能器系统及其联合治疗的可行性和毒性 与应计能力一起，确定治疗方法的技术 在准备局部试验2期试验中的疗效和分层 肿瘤控制将在不同的热剂量下结合IORT和IOHT。 本研究的工程开发和临床试验部分 将在达斯茅斯-希区柯克医疗中心演出， 动物周围神经耐受部分将在 科罗拉多州立大学兽医教学医院。