OPTIMIZATION OF HYPERTHERMIA:BIOL & PHYSICAL STUDIES

在20世纪70年代和80年代早期，热疗被证明具有显著的 提高人类癌症治愈率的潜力，因为临床前 高温和X射线照射之间相互作用的研究， 抗癌药物的积极作用是如此的令人信服。 迄今为止，高温可能 已经被证明可以增加乳腺癌的放射性控制 胸壁复发和头颈部大结节 癌症，但对患者的可治愈性（即总生存期）有影响 与这些或其他肿瘤的关系还没有记录。 我们认为 热疗尚未充分发挥其临床潜力的原因是 因为它的生物学相互作用和输送的物理学原理 还有待优化。 这两个因素都将在 本申请中提出的工作。 本计划中相互关联的项目将试图改善 临床上有用的生物学热疗：1）更好地定义 负责耐热性的机制，这样我们就可以尝试 选择性抑制恶性组织中的耐热性发展，和， 因此，使更频繁的热疗合理的分割（博士。 Calderwood，项目I）; 2）探索全身热疗（WBH）作为一个 一系列抗癌烷化剂（AA's）的正调节剂 + 复杂动物模型中的局部辐射（Teicher博士，项目II）; 和3）继续开发最大有效的抗癌组合， 药物、局部放疗和高温（赫尔曼博士，项目 （五）。 该计划项目还将试图改善的物理 通过以下方式提供热疗：1）测试和改进 诊所中的新型聚焦分段超声机（FSUM）（赫尔曼博士， 2）开发新的三维计算机建模能力， 与FSUM接口（Svensson博士，项目III）; 3）利用间隙 可以密集测量组织温度以及组织温度的探头 灌注（鲍曼博士，项目IVa）;和4）开发简化的3-D 可以在真实的时间内使用的温度模型， FSUM治疗（纽曼博士，项目IVb）。

In the 1970's and early 1980's hyperthermia was shown to have substantial potential to increase the curability of human cancer because preclinical studies of the interaction between hyperthermia and x-irradiation or anticancer drugs were so compellingly positive. To date, hyperthermia may have been shown to increase radiotherapeutic control of breast cancer recurrent on the chest wall and large neck nodes from head and neck cancers, but an impact on curability (i.e. overall survival) of patients with these or other tumors has not been documented. We believe that the reasons why hyperthermia has not reached its full clinical potential are because both its biological interactions and the physics of its delivery have yet to be optimized. Both of these factors will be addressed in the work proposed in this application. The interrelated Projects in this program will attempt to improve the clinically useful biology of hyperthermia by: 1) better defining the mechanisms responsible for thermotolerance so that we can attempt to selectively inhibit thermotolerance development in malignant tissues, and, thus, make more frequent fractionation of hyperthermia rational (Dr. Calderwood, Project I); 2) exploring whole body hyperthermia (WBH) as one of a series of positive modulators of anticancer alkylating agents (AA's) + local radiation in sophisticated animal models (Dr. Teicher, Project II); and 3) continuing to develop maximally effective combinations of anticancer drugs, local radiation and hyperthermia in the clinic (Dr. Herman, Project V). The Program Project will also attempt to improve the physics of hyperthermia delivery by: 1) testing and refining the capabilities of a new Focused, Segmented Ultrasound Machine (FSUM) in the clinic (Dr. Herman, Project V); 2) developing new 3-D computer modelling capabilities to interface with FSUM (Dr. Svensson, Project III); 3) utilizing interstitial probes which can measure tissue temperatures densely as well as tissue perfusion (Dr. Bowman, Project IVa); and 4) developing simplified 3-D temperature models which can be used in real time to improve patient treatments with the FSUM (Dr. Newman, Project IVb).