HYPERTHERMIA AND PERFUSION EFFECTS IN CANCER THERAPY

该计划的长期目标是优化 热疗（HT）作为放疗（RT）和/或化疗的辅助。 这种治疗的优化取决于五个领域的进展： l）开发更准确和侵入性更小的方法来测量三个 三维非均匀温度分布，2）建立一个 与治疗相关的准确和可量化的HT剂量测定 结果，3）开发识别最有可能 从HT中获益，4）开发方法以增强治疗 HT的功效和3）开发技术上能够 达到所需的热剂量，根据剂量效应 问题研究该计划的核心重点是基于三个临床 将前瞻性测试的潜在治疗优势的试验 当与RT结合时，高与低HT剂量。这些试验代表了 进行首次前瞻性HT剂量递增试验，如果 如果成功，他们将建立HT剂量测定的定量基础， 可以更好地在所有患者中应用这种治疗。 项目I将使用RT测试高与低HT剂量，用于治疗软组织 宠物狗的组织肉瘤 项目二将评估各种方法， 通过急性降低肿瘤内pH值或通过减少肿瘤 血液流动，以便更好地加热。 项目三包含所有人类 协议.浅表肿瘤和软组织肉瘤的治疗方案将 比较接受高剂量或低剂量HT的患者组的结果， 另一种方案将比较患者特异性 计算机生成的功率沉积模型，以确定最佳的 优化方案，以实现最高温度从环形相 阵列射频器件。最终方案将继续进行第1阶段测试， 顺铂腹腔注射联合局部HT治疗晚期 复发性卵巢癌项目四将采用完整的热模拟， 作为重建三维温度的手段 分布，并将模拟非均匀温度的影响 微环境条件对肿瘤细胞存活的影响 HT+ RT。项目V将继续调查31-P的潜力 磁共振波谱、MR灌注成像和pO 2组织图 预测和监测人类和犬肿瘤对HT+ RT的反应。支持 这些努力将由行政，生物统计， 动物和工程核心。在工程方面的发展努力 核心包括MR化学位移成像的非侵入性评价 温度测量和工程的新喷头的高温处理的一个 各种肿瘤。

The long term goal of this program is to optimize the application of hyperthermia (HT) as an adjuvant to radiotherapy (RT) and/or chemotherapy. Optimization of this treatment is dependent upon progress in five areas: l) development of more accurate and less invasive means to measure three dimensional non-uniform temperature distributions, 2) establishment of an accurate and quantifiable HT dosimetry that correlates with treatment outcome, 3) development of means to identify patients who are most likely to benefit from HT, 4) development of methods to enhance the therapeutic efficacy of HT and 3) development of equipment that is technically capable of achieving desired thermal doses, as established from dose effect studies. The central focus of the program is based on three clinical trials that will prospectively test the potential therapeutic advantage of high vs low HT doses when combined with RT. These trials represent the first prospective HT dose escalation trials to be performed, and if successful, they will establish a quantitative basis for HT dosimetry that could lead to better application of this treatment in all patients. Project I will test high vs low HT doses with RT for treatment of soft tissue sarcomas in pet dogs. Project II will evaluate methods to enhance HT sensitivity by acutely reducing intratumoral pH or by reducing tumor blood flow to allow for better heating. Project III contains all human protocols. Protocols in superficial tumors and soft tissue sarcomas will compare outcome in groups of patients who receive high or low HT doses in combination with RT. Another protocol will compare patient specific computer generated models of power deposition to determine best optimization schemes to achieve highest temperatures from annular phased array RF devices. The final protocol will continue Phase 1 testing of intraperitoneal cisplatin with regional HT for the treatment of advanced recurrent ovarian cancer. Project IV will employ full thermal modeling of actual patients as a means to reconstruct three dimensional temperature distributions and will model the influence of non-uniform temperature fields and micro environmental conditions on tumor cell survival after HT+RT. Project V will continue investigation of the potential of 31-P magnetic resonance spectroscopy, MR Perfusion Imaging and pO2 histography to predict and monitor human and canine tumor response to HT+RT. Support for these efforts will be provided by administrative, biostatistics, animal and engineering cores. Developmental efforts in the engineering core include the evaluation of MR chemical shift imaging for non-invasive thermometry and the engineering of new applicators for HT treatment of a variety of tumors.