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

总结 局部前列腺癌可以在5个疗程中使用一种精确的靶向放射治疗， 立体定向放射治疗（SBRT），毒性低。尽管取得了这些进展， 侵袭性（高风险）前列腺癌仍然很差，10年无复发生存率约为65% 无论治疗方式如何。复发通常距离较远，预后差，5年 存活率25%。我们建议利用癌症成像（PSMA正电子发射）的最新进展， 断层扫描（PET）/磁共振成像（MR））和放射治疗（MR引导放射治疗 实时适应性计划），以提供针对以下区域的个性化放射治疗： 前列腺复发风险最大，精度提高，从而改善临床结局 前列腺癌的治疗方法PSMA PET/MR是一种新的成像模式，尚未广泛应用于临床。 PSMA PET与MR的结合， 改善前列腺内结节的描绘，提高转移性前列腺癌的诊断准确性 与传统影像学相比。PSMA PET/MR成像数据可轻松传输到基于MR的 直线加速器（MR-LINAC），一种新型的创新平台，允许在手术过程中直接观察肿瘤。 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校正。 通过结合上级治疗前成像，增强了对高危前列腺内 结节的复发风险最大，精确的MR引导实时自适应放射治疗，我们 假设可以减少局部和远处复发。我们还将利用PSMA PET/MR和活检 在SBRT后1年，以表征治疗反应并更早地检测疾病复发。来测试我们 假设，我们将利用PSMA PET/MR引导的SBRT进行单组II期临床试验， 靶向剂量递增至MR-LINAC上的主要前列腺内结节。这方面的总体范围 一项建议是利用先进的PET和MR成像和治疗，以提高治疗指数 SBRT在高危前列腺癌中的应用，最大限度地提高治疗效果，同时最大限度地减少毒性。如果成功，这 一项提案将指导新兴成像技术（PSMA PET/MR和MR-LINAC）的使用 在未来几年内增加可用性和使用），并引入一种新的治疗模式 具有显著改善前列腺癌预后的潜力。

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.