Molecular Imaging with FACBC PET-CT to Improve Post prostatectomy Radiotherapy

使用 FACBC PET-CT 进行分子成像以改善前列腺切除术后的放射治疗

• 批准号: 8348376
• 负责人: Ashesh Jani
• 金额: $ 45.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8348376
• 关键词: Algorithms; Beds; Belief; Biochemical; Biometry; Biopsy; Bladder; Cancer Control; Cancer Patient; Carboxylic Acids; Carcinoma; Clinical; Data; Decision Making; Dose; Extraprostatic; Failure; Goals; Image; Malignant neoplasm of prostate; Medical Oncology; Outcome; Patient Selection; Patients; Pelvic lymph node group; Pelvis; Population; Positron-Emission Tomography; Prostate; Prostate carcinoma; Prostate-Specific Antigen; Prostatectomy; Prostatic; Public Health; Radiation; Radiation therapy; Randomized; Randomized Clinical Trials; Rectum; Recurrence; Role; Structure; Systemic disease; Testing; Toxic effect; Urology; Work; arm; base; conventional therapy; cost effectiveness; image registration; imaging modality; improved; molecular imaging; multidisciplinary; novel; prospective; radiotracer; randomized trial; response; treatment planning

DESCRIPTION (provided by applicant): Our overall goal is to improve the long term biochemical free survival of patients with recurrent prostate carcinoma by altering the current decision algorithm through the ability of advanced molecular imaging to guide the appropriate selection of patients who will benefit from salvage radiotherapy. Approximately 50% of patients who have undergone post-prostatectomy radiotherapy after Prostate Specific Antigen (PSA) failure or biopsy proven prostate bed recurrence manifest subsequent systemic disease, in part, because conventional imaging methods fail to adequately differentiate prostatic from extraprostatic recurrence. In the post-prostatectomy setting, both under-treatment and over- treatment occur based on existing strategies, and appropriately directing radiotherapy is an unmet public health need in this population. We plan to leverage advanced molecular imaging with the positron emission tomography (PET) radiotracer anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) which in preliminary data is able to differentiate prostatic from extra-prostatic recurrence even at low PSA levels. Doing so will enable more appropriate selection of patients who will benefit from salvage radiotherapy and to achieve durable response at higher PSA levels than previously believed. We hypothesize that if patients are appropriately selected for salvage radiotherapy with the aid of newly available advanced molecular imaging with anti-3-[18F]FACBC PET-CT, a significantly higher proportion will achieve long-term cure and at higher PSA levels than via conventional treatment algorithms. We also hypothesize that the use of advanced molecular imaging will alter post-prostatectomy radiotherapy algorithms both in decision to treat and in planning volumes. To test these two hypothesis, we plan to conduct a prospective randomized clinical trial in which patients will be treated with salvage radiotherapy after conventional imaging methods in the control arm (A) and with the addition of anti-3-[18F]FACBC PET-CT in the trial arm (B). We will explore the role of anti-3-[18F]FACBC PET-CT in (1) controlling prostate cancer that would otherwise generally not be treated with post- prostatectomy radiotherapy, and improving prostate cancer control in patients that would generally be considered for radiotherapy, (2) guiding radiotherapy decisions, both in the overall decision to offer radiotherapy and in the decision to guide the general radiation field (prostate bed versus pelvis), and (3) influencing the target volume and overlap of normal structures when planning and delivering radiotherapy. The work will have significant implications for improving the outcomes of post-prostatectomy patients, not just for the use of anti-3-[18F]FACBC but for the application of novel imaging to guide post-prostatectomy radiotherapy. PUBLIC HEALTH RELEVANCE: Advanced Molecular Imaging with anti-3-[18F]FACBC PET-CT to Improve the Selection and Outcomes of Prostate Cancer Patients Receiving Post-prostatectomy Radiotherapy Project Narrative/Relevance Failure of prostate cancer treatment is a significant health problem. Radiotherapy is often used after surgical failures, but the conventional imaging techniques currently used to guide radiotherapy decisions and treatment planning are quite limited. The overall goal of the proposal establish the role of advanced molecular imaging, with focus on one particular novel radiotracer (anti-3-[18F]FACBC) for which there is significant preliminary data, in improving the selection of patients for post-prostatectom radiotherapy and in improving prostate cancer outcomes.

描述（由申请方提供）：我们的总体目标是通过先进的分子成像技术指导适当选择将从挽救性放疗中获益的患者，从而改变当前的决策算法，提高复发性前列腺癌患者的长期无生化生存期。在前列腺特异性抗原（PSA）失败或活检证实的前列腺床复发后接受前列腺切除术后放疗的患者中，约50%表现出随后的全身性疾病，部分原因是常规成像方法无法充分区分前列腺和前列腺外复发。在子宫切除术后的环境中，基于现有策略，治疗不足和过度治疗都发生，并且适当定向放射治疗是该人群中未满足的公共卫生需求。我们计划利用正电子发射断层扫描（PET）放射性示踪剂抗1-氨基-3-[18 F]氟环丁烷-1-羧酸（抗3-[18 F] FACBC）的先进分子成像，初步数据显示，即使在低PSA水平下，也能够区分前列腺和前列腺外复发。这样做将能够更适当地选择将从挽救性放疗中受益的患者，并在比之前认为的更高的PSA水平下实现持久反应。我们假设，如果患者在抗3-[18 F] FACBC PET-CT的最新先进分子成像的帮助下被适当选择接受挽救性放疗，那么与传统治疗算法相比，实现长期治愈和PSA水平更高的比例将显著更高。我们还假设，先进的分子成像技术的使用将改变直肠癌切除术后的放射治疗算法，无论是在决定治疗和规划体积。为了检验这两个假设，我们计划进行一项前瞻性随机临床试验，在对照组（A）中，患者将在常规成像方法后接受补救放疗，在试验组（B）中，患者将接受抗3-[18 F] FACBC PET-CT治疗。我们将探索抗3-[18 F] FACBC PET-CT在以下方面的作用：（1）控制前列腺癌，否则通常不会用前列腺切除术后放疗治疗，并改善通常考虑放疗的患者的前列腺癌控制，（2）指导放疗决策，无论是在提供放射治疗的总体决策中，还是在指导一般放射领域的决策中，（前列腺床对骨盆），和（3）在计划和递送放射治疗时影响目标体积和正常结构的重叠。这项工作将对改善乳腺癌切除术后患者的预后具有重要意义，不仅是使用抗3-[18 F] FACBC，而且是应用新型成像技术指导乳腺癌切除术后放疗。 公共卫生关系：抗3-[18F] FACBC PET-CT先进分子成像改善接受前列腺切除术后放射治疗的前列腺癌患者的选择和结局项目叙述/相关性前列腺癌治疗失败是一个重要的健康问题。放射治疗通常在手术失败后使用，但目前用于指导放射治疗决策和治疗计划的传统成像技术非常有限。该提案的总体目标是确定先进分子成像的作用，重点是一种特殊的新型放射性示踪剂（抗3-[18 F] FACBC），其具有重要的初步数据，可改善患者接受前列腺切除术后放疗的选择和改善前列腺癌结局。