PSMA/MR-guided Stereotactic Body Radiotherapy for High Risk Prostate Cancer

摘要 局部前列腺癌可以在5个疗程内使用一种精确的、靶向的放射治疗，称为 立体定向全身放射治疗(SBRT)，毒性低。尽管取得了这些进展，但 侵袭性(高风险)前列腺癌仍然很差，10年无复发存活率约为65% 无论治疗方式如何。复发通常较远，预后较差，一般为5年。 存活率为25%。我们建议利用癌症成像的最新进展(PSMA正电子发射 体层摄影术(PET)/磁共振成像(MR))和放射治疗(MR引导的放射治疗 具有实时自适应规划)，以提供针对以下领域的个性化放射治疗 提高精确度，提高前列腺癌复发的风险，从而改善临床结果 适用于前列腺癌高危人群。PSMA PET/MR是一种新的成像方式，目前还没有广泛应用 可用，这增加了MR提供的组织细节PSMA PET与MR的组合结果在 改善前列腺内结节的勾画，提高诊断转移性病变的准确率 疾病与常规成像相比。PSMA PET/MR成像数据可以很容易地传输到基于MR的 直线加速器(MR-LINAC)，这是一种新颖的创新平台，允许在 治疗，并允许通过在线自适应放射计划对运动进行实时个性化矫正。 通过结合卓越的治疗前成像，增强对高危前列腺内的识别 复发风险最大的结节，以及精确的MR引导的实时自适应放射治疗，我们 假设本地和远程递归可以减少。我们还将使用PSMA PET/MR和活检 在SBRT后1年，以确定治疗反应并及早发现疾病复发。测试我们的 假设，我们将使用PSMA PET/MR引导的SBRT进行单臂II期临床试验， MR-LINAC上对显性前列腺内结节(S)的定向剂量递增。这件事的总体范围 建议利用先进的基于PET和MR的成像和治疗来提高治疗指数 SBRT在高危前列腺癌中的应用，在最大限度地提高治疗效果的同时将毒性降至最低。如果成功，这将是 建议书将指导新兴成像技术的使用(预计将使用PSMA PET/MR和MR-LINAC 以在未来几年增加可用性和使用率)并引入一种新的治疗范例 有可能显著改善前列腺癌的预后。

Summary Localized prostate cancer can be treated in 5 sessions using a precise, targeted form of radiation known as stereotactic body radiation therapy (SBRT), with low toxicity. Despite these advances, overall outcomes for aggressive (high risk) prostate cancer remain poor, with 10-year recurrence-free survival of approximately 65% regardless of treatment modality. Recurrences are typically distant and carry poor prognosis, with 5 year survival of 25%. We propose to utilize the latest advances in cancer imaging (PSMA Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MR)) and radiation delivery (MR-guided radiation therapy with real-time adaptive planning), to deliver a personalized radiation treatment that targets the areas of greatest risk of recurrence in the prostate with improved precision, and as a result improve clinical outcomes for individuals with high risk prostate cancer. PSMA PET/MR is a novel imaging modality, not yet widely available, that augments the tissue detail provided by MR. The combination of PSMA PET with MR results in improved delineation of intraprostatic nodules and higher diagnostic accuracy for detection of metastatic disease compared to conventional imaging. PSMA PET/MR imaging data is readily transferable to a MR-based linear accelerator (MR-LINAC), a novel, innovative platform that allows direct visualization of the tumor during treatment, and permits real-time individualized correction for motion with online adaptive radiation planning. Through incorporation of superior pre-treatment imaging, enhanced identification of high risk intraprostatic nodules at greatest risk of recurrence, and precise MR-guided real-time adaptive delivery of radiation, we hypothesize that local and distant recurrences can be reduced. We will also utilize PSMA PET/MR and biopsy at 1 year after SBRT to characterize treatment response and detect disease recurrences earlier. To test our hypotheses, we will conduct a single arm, phase II clinical trial utilizing PSMA PET/MR guided SBRT with targeted dose-escalation to dominant intraprostatic nodule(s) on an MR-LINAC. The overarching scope of this proposal is to harness advanced PET and MR-based imaging and treatment to enhance the therapeutic index of SBRT in high risk prostate cancer, maximizing treatment efficacy while minimizing toxicity. If successful, this proposal will guide utilization of emerging imaging technologies (PSMA PET/MR and MR-LINACs are expected to increase in availability and usage over the next several years) and introduce a novel treatment paradigm with the potential to significantly improve prostate cancer outcomes.