Intraoperative Dose Visualization using X-Ray and Ultrasound for Prostate Brachyt

描述(申请人提供)：近距离放射治疗被广泛应用于前列腺癌的治疗；在美国每年进行超过55,000例手术。近距离放射治疗的流行是由于它的微创性质和患者对时间的适度投入。它的成功取决于给前列腺提供足够的剂量，同时避免对邻近器官的过度辐射。尽管在技术上有所改进，并从选定的中心公布了出色的结果，但当代的多中心报告和质量保证计划记录了结果的相当大的变异性，随之而来的是毒性和次优结果。公认的导致剂量学结果不佳的主要因素是源定位错误、源可视化差和前列腺水肿，这些因素共同导致剂量过高和不足的两个区域。在手术过程中，对放射源的动态可视化和术中剂量重建的迫切需要被广泛认识到。术中剂量优化有望极大地改变近距离放射治疗的护理标准，使医生能够精确地根据患者的解剖结构定制剂量，并在手术完成之前获得准确的剂量可视化和反馈。这就要求术中根据前列腺和周围解剖来定位植入物。我们建议开发一种临床可行的图像引导平台，能够动态、精确和定量地评估近距离放射治疗中的剂量。这将允许对源位置改变进行持续校正，并产生最佳植入物，从而降低毒性并改善癌症控制。目标1：动态剂量学的发展：为术中剂量学和植入物优化开发系统概念和算法。这一结果将是一种基于软件的、实用的真实术中剂量可视化方法。该系统将不需要对临床硬件进行重大更改，并将最大限度地改变传统的临床工作流程，使其能够转化为广泛使用。目标2：系统实施和验证：将系统组件技术实施为适合临床使用的近距离放射治疗剂量学套件，并在术中对动态剂量学系统进行评估。将进行完整的文件记录，并在模体中验证其技术准确性和健壮性，随后将进行试点临床研究，以验证该系统并评估其性能和术中使用的适宜性。这些信息将被输入到目标3的系统更新中。目标3：临床假设和试验：利用单个系统组件进行IRB批准的试验，以及对完全集成的系统进行最终研究，以便对照一套严格的基准来确定性能，并与当前可用的标准方法进行比较。对结果的估计将在未来更大的第二阶段研究中得到证实。 公共卫生相关性：在美国，每年约有19.2万名男性被诊断患有前列腺癌，使其成为困扰男性的最常见癌症，在总人口中排名第二。近距离放射治疗(将放射性粒子植入前列腺癌)被广泛用于前列腺癌的治疗，但研究表明，男性接受次优近距离放射治疗的情况很常见，剂量要么不足(导致癌症复发的风险)，要么太高(导致副作用，有时还会产生严重毒性)。造成这些结果的一个主要因素是，在植入种子时，医生缺乏现有的技术来可视化或‘看到’前列腺内的辐射剂量；拟议的研究的目标是开发一种系统，以一种可以在全国范围内广泛实施的方式实现这一能力。

DESCRIPTION (provided by applicant): Brachytherapy is widely utilized in the management of prostate cancer; over 55,000 procedures are performed in the US annually. The prevalence of brachytherapy is due to its minimally invasive nature and modest time commitment on the part of the patient. Its success hinges on adequately dosing the prostate while avoiding excessive radiation to adjacent organs. Despite some improvements in technique and excellent published results from select centers, contemporary multi-center reports and quality assurance programs document considerable variability in results, with ensuing toxicity and suboptimal outcomes. Well-recognized major contributors to poor dosimetric results are source positioning errors, poor source visualization, and prostatic edema, which in aggregate lead to both regions of excessive as well as inadequate dose. The critical need for dynamic visualization of sources and intraoperative dose reconstruction during the procedure is broadly recognized. Intraoperative dose optimization promises to dramatically change the standard of care in brachytherapy by allowing the physician to precisely tailor the dose to the individual patient's anatomy, as well as obtain accurate dose visualization and feedback prior to procedure completion. This requires intra-operative localization of the implant in relation to the prostate and surrounding anatomy. We propose the development of a clinically feasible image-guidance platform with capability for dynamic, precise and quantitative evaluation of dose during brachytherapy. This will allow for ongoing correction for source position alterations and result in an optimal implant, leading to reduced toxicity and improved cancer control. Aim 1: Development of Dynamic Dosimetry: Develop a system concept and algorithms for intraoperative dosimetry and implant optimization. The result will be a software-based, practical method for true intra-operative dose visualization. The system will not require significant changes in clinical hardware and will minimally alter customary clinical workflow, making it feasible for translation into widespread use. Aim 2: System Implementation and Validation: Perform technical implementation of the system components into a brachytherapy dosimetry suite suitable for clinical use and evaluation of the dynamic dosimetry system intraoperatively. Full documentation and verification of its technical accuracy and robustness in phantoms will be conducted, followed by pilot clinical studies to validate the system and assess performance and suitability for intraoperative use. This information will be fed into system updates for Aim 3. Aim 3: Clinical Hypothesis and Trial: Perform IRB-approved trials utilizing individual system components, as well as a final study of the fully integrated system, in order to establish performance against a rigorous set of benchmarks and to compare with currently available standard methods. Estimates of outcomes will be obtained for confirmation in a future, larger Phase II study. PUBLIC HEALTH RELEVANCE: Prostate cancer is diagnosed in approximately 192,000 men per year in the United States, making it the most common cancer afflicting men and second most common in the overall population. Brachytherapy (implantation of radioactive seeds into the prostate) is widely used in the treatment of prostate cancer, yet studies show that it is common for men to receive suboptimal brachytherapy treatment, with doses either insufficient (leading to risk of cancer recurrence) or too high (leading to side effects and sometimes serious toxicity). A major contributor to these outcomes is the lack of existing techniques for physicians to visualize or 'see' radiation dose within the prostate as seeds are implanted; the goal of the proposed research is to develop a system which achieves this capability in a manner that can be readily implemented in operating rooms on a widespread scale nationwide.