Multiparametric MRI-guided Prostate HDR Brachytherapy with Focal Tumor Boost

项目总结/摘要 前列腺癌影响美国六分之一的男性。尽管技术进步，前列腺放射治疗仍然 导致高风险前列腺癌患者的局部控制和生存不良-超过50%的患者 患有高危疾病的患者在前列腺放疗后会复发。组织学研究表明 前列腺内的主要癌灶与放疗后局部复发的部位有关。它 已经证明，最先进的多参数MRI（mp-MRI）结合解剖成像与 功能性MRI技术是诊断前列腺内显性病变（DIL）的最佳方法。 高剂量率（HDR）近距离放射治疗，具有精确的辐射剂量输送、放射生物学优势和较低的 成本，已经成为前列腺癌患者日益流行的治疗方式。一些研究在 HDR近距离放射治疗已经表明，使用整个前列腺治疗的DIL的放射治疗增强可以改善 局部肿瘤控制而不引起过量毒性。然而，由于DIL的解剖位置和大小， 大约60%的患者无法在不增加器官功能的情况下达到预期的DIL加强剂量覆盖率， 在风险（OAR）容限在当前的HDR提升实践。我们假设DIL靶向HDR导管 放置将显著改善聚焦增强HDR中DIL的可实现增强剂量覆盖 近距离放射治疗拟议的研究是开发一种以DIL为靶点的超声引导HDR前列腺近距离放射治疗 聚焦增强具体而言，我们建议开发一种新的MRI-US-CT变形配准， 将mp-MRI定义的DIL整合到实时US中，以指导HDR导管放置，从而提高 可实现的最佳剂量增强，以及平移CT以引导HDR治疗中的局灶性DIL增强剂量输送。 这个整体项目是建立在三个组成部分：1）PI的获奖前列腺分割和 配准技术，2）mp-MRI提供的DIL信息，以及3）精确的辐射输送 HDR近距离放射治疗技术提供的系统。引入DIL靶向HDR的潜在益处 增强近距离放射治疗，可以照射整个前列腺，同时局部增强更高剂量 对mp-MRI定义的DILs的影响是巨大的。在这个项目中，我们将1）开发和优化前列腺分割 和配准算法，2）定量评估这些算法的一致性和准确性， 体模和患者数据，以及3）评估所提出的DIL靶向增强HDR的性能， 常规HDR近距离放射治疗并检查其临床益处。该项目的成功完成将 克服了推进前列腺癌个性化HDR近距离放射治疗的关键障碍，从而提供了 一种局部增加DIL辐射剂量的方法，同时保留正常组织以改善局部控制， 前列腺癌患者的长期生存率和生活质量，特别是晚期前列腺癌患者 癌

Project Summary/Abstract Prostate cancer affects 1 in 6 men in USA. Despite the technological advances, prostate radiotherapy still results in poor local control and survival for patients with high-risk prostate cancer – over 50% of the patients with high-risk disease will experience relapses following prostate radiotherapy. Histopathologic studies showed that dominant cancer foci within the prostate are associated with sites of local recurrence post radiotherapy. It has been proven that the state-of-the-art multiparametric MRI (mp-MRI) combining anatomic imaging with functional MRI techniques can provide the best performance to define dominant intraprostatic lesion (DIL). High-dose-rate (HDR) brachytherapy, with precise radiation-dose delivery, radiobiological advantage and lower cost, has become an increasing popular treatment modality for patients with prostate cancer. A few studies in HDR brachytherapy have shown that radiotherapy boost for a DIL with whole prostate treatment can improve local tumor control without causing excess toxicity. However, due to the anatomic location and size of a DIL, approximate 60% patients could not achieve the expected DIL boost dose coverage without increasing organ- at-risk (OAR) tolerances in current HDR boost practice. We hypothesize that DIL-targeted HDR catheter placement will significantly improve achievable boost dose coverage for DILs in focal boost HDR brachytherapy. The proposed research is to develop a DIL-targeted, US-guided HDR prostate brachytherapy with focal boost. Specifically, we propose to develop a novel MRI-US-CT deformable registration, which can incorporate mp-MRI-defined DIL into real-time US to guide HDR catheters placement to improve the probability of achievable optimal dose boost, and panning CT to guide focal DIL boost dose delivery in HDR treatment. This overall project is built on three integral components: 1) the PI’s award-winning prostate segmentation and registration technologies, 2) the DIL information provided by mp-MRI, and 3) a precise radiation delivery system offered by the HDR brachytherapy technique. The potential benefit of introducing DIL-targeted HDR boost brachytherapy that can irradiate the whole prostate while simultaneously and focally boost a higher dose to mp-MRI-defined DILs is enormous. In this project, we will 1) develop and optimize prostate segmentation and registration algorithms, 2) quantitatively evaluate the consistency and accuracy of these algorithms using phantom and patient data, and 3) evaluate the performance of the proposed DIL-targeted boost HDR with conventional HDR brachytherapy and examine its clinical benefit. Successful completion of this project will overcome a critical barrier to advance personalized HDR brachytherapy for prostate cancer, thus providing a way to focally boost the radiation dose to the DILs while sparing the normal tissue to improve local control, long-term survival and quality of life for prostate-cancer patients, particularly those with advanced prostate cancer.