Feasibility of a New Thermo-brachytherapy Seed for Concurrent Brachytherapy and H

描述(由申请人提供)：在过去的三十年里，在癌症治疗中对放射治疗和热疗的辅助管理进行了广泛的研究(Deger等人，2004年)，但使用相同来源同时提供这些方式还没有文献记载。在这里，我们提出了一种新的近距离热疗种子的可行性研究、开发和临床应用，该种子将密封的放射源和铁磁芯结合在一起，当放置在交变电磁场中时，作为自动调节热疗源。拟议的新种子是基于传统的125I粒子，通常用于前列腺癌植入，并增加了一个铁磁性核心，以取代作为热源的钨标记。除了在癌症治疗开始时用作辐射和热源外，这些植入的种子还可以在肿瘤复发时用于肿瘤的热再治疗，可能是作为全身治疗的增敏剂，而不需要另一种侵入性程序。磁场和自我调节种子的结合将排除侵入性测温的需要，并提供相对容易的热传递，特别是对深层肿瘤。该方法利用铁磁性金属合金的居里温度来实现热自调节，该温度与其成分不同，从而导致达到目标处理温度范围后的产热量急剧下降。这一创新与临床上可用的技术形成了鲜明对比，在临床上，热疗是通过微波和超声波喷射器进行的，导致渗透有限，并且固有地需要侵入性测温。该项目的目标包括：使用蒙特卡罗模拟完成对这种新开发的双功能SEED的剂量学表征和评估，以及使用有限元建模对其热性能进行表征和评估。通过与托莱多大学的合作，我们的目标是开发和制造一种原型，并研究其在同时提供辐射和热量方面的功效。为该项目召集的跨学科专家团队涵盖了拟议项目的所有预期方面，包括科学、工程和临床问题，从而确保成功实现所设定的具体目标。第一阶段的成功完成将推动该项目进入全功能SEED原型开发的第二阶段。将原型相继转化为同时进行前列腺癌近距离放射治疗和热疗的高效临床程序，将为立即商业化提供热后装治疗种子。 与公共健康相关：根据美国癌症协会发布的统计数据，仅在美国，估计今年就有近187000名男性得知前列腺癌的消息，其中约六分之一会死于前列腺癌。该项目中提出的技术有可能降低这一比例，增加肿瘤控制的可能性，而不会对目前提供的治疗方案进行重大改变。通过创新技术和对现有放射性植入物的改进，可以将辅助分次热疗整合到放射传递程序中，并在失败的情况下通过已植入的种子重新加热腺体来进行挽救治疗。

DESCRIPTION (provided by applicant): Adjuvant administration of radiation therapy with hyperthermia in treatment of cancer has been studied extensively in the past three decades (Deger et al., 2004), but simultaneous delivery of these modalities using the same source has not been documented. Here we propose feasibility study, development and clinical implementation of a new Thermo-brachytherapy seed that combines a sealed radioactive source with a ferromagnetic core serving as a self-regulating hyperthermia source when placed in an alternating electromagnetic field. The proposed new seed is based on the conventional 125I seed commonly used for prostate implant with addition of a ferromagnetic core in place of the tungsten marker to be implemented as a heat source. In addition to being used as a source for both radiation and heat at the onset of cancer therapy, these implanted seeds could be used for thermal re-treatment of the tumor in case of recurrence, possibly as a sensitizer to systemic therapies without another invasive procedure. The combination of a magnetic field and a self-regulating seed will preclude the need for invasive thermometry and provides relative ease of the heat delivery especially to deep-seated tumors. With this approach heat self-regulation is achieved by employing the Curie temperature of a ferromagnetic metallic alloy, distinct to its composition, leading to drastic decrease in heat production after reaching the targeted treatment temperature range. This innovation is in contrast to clinically available technology where hyperthermia is delivered by microwave and ultrasound applicators resulting in limited penetration and the inherent need for invasive thermometry. The goals for this project include: complete dosimetric characterization and evaluation of this newly developed dual function seed using Monte Carlo simulation, and characterization and evaluation of its thermal properties using the finite element modeling. Through our partnership with the University of Toledo we aim at development and manufacturing of a prototype, and studying its efficacy in concurrent delivery of radiation and heat. The interdisciplinary team of experts assembled for this project covers all anticipated aspects of the proposed project, including scientific, engineering, and clinical issues, thus ensuring the successful achievement of the specific aims set forth. Successful completion of the Phase I will propel the project into the Phase II stage of development of a fully functional seed prototype. Successive translation of the prototype into a highly effective clinical procedure of concurrent administration of brachytherapy and hyperthermia for prostate cancer treatments will prepare Thermo- brachytherapy seed for immediate commercialization. PUBLIC HEALTH RELEVANCE: Of the nearly 187000 men estimated to get the news for prostate cancer this year in US alone, about 1 in 6 will die from it based on statistics published by the American Cancer Society. The technique proposed in this project has the potential to reduce this ratio and increase the probability of tumor control without a significant change in treatment regimen currently offered. Through an innovative technology and modification of an existing radioactive implant, an adjuvant fractionated hyperthermia treatment can be integrated into radiation delivery procedure, and can be used for salvage therapy in case of a failure by re-heating the gland via the already implanted seeds.