HYPERTHERMIA AND PERFUSION EFFECTS IN CANCER THERAPY

该计划的长期目标是优化应用 热疗(HT)作为放疗和/或化疗的辅助手段。 这种治疗的优化取决于五个方面的进展： L)开发更准确、更少侵入性的测量方法 空间非均匀温度分布，2)建立了一种 与治疗相关的准确和可量化的羟色胺剂量测定 结果，3)开发方法来识别最有可能 从高血压中受益，4)开发提高治疗效果的方法 HT的功效和3)技术能力强的设备的发展 根据剂量效应确定的实现所需热剂量的方法 学习。该计划的中心重点是基于三个临床 将前瞻性测试潜在的治疗优势的试验 高剂量羟色胺与低剂量羟色胺联合放射治疗。这些审判代表着 将进行的第一个前瞻性的HT剂量递增试验，如果 如果成功，他们将为HT剂量测定建立一个量化基础 可以使这种治疗在所有患者中得到更好的应用。 项目I将通过RT治疗软组织来测试高剂量和低剂量的羟色胺。 宠物狗的组织肉瘤。项目II将评估方法以增强 通过显著降低瘤内pH值或通过减少肿瘤来提高羟色胺敏感性 血液流动，以实现更好的加热。项目III包含所有人类 协议。浅表肿瘤和软组织肉瘤的治疗方案 比较接受高剂量和低剂量羟色胺治疗的患者组的结果 与RT相结合。另一种方案将比较患者的具体情况 计算机生成的功率沉积模型，以确定最佳 从环状分阶段实现最高温度的优化方案 阵列射频设备。最终协议将继续进行第一阶段测试 顺铂联合局部羟色胺治疗晚期肺癌 复发性卵巢癌。项目IV将采用全热模拟技术 真实病人作为重建三维温度的手段 非均匀温度影响的分布和Will模型 电场和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PO2组织成像 目的：预测和监测人和犬肿瘤对HT+RT的反应。支持 因为这些努力将由行政、生物统计、 动物和工程核心。工程中的发展努力 核心包括非侵入性磁共振化学位移成像的评价 高温热疗机的测温及新型施加器的研制 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.