PET-determined prostate brachytherapy dosing using intraoperative image-guidance

使用术中图像引导 PET 确定前列腺近距离放射治疗剂量

• 批准号: 9382210
• 负责人: Everette C Burdette
• 金额: $ 53.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9382210
• 关键词: Algorithms; Anatomy; Assessment tool; Brachytherapy; Cancer Control; Cancer Etiology; Cancer Survivor; Cancerous; Cessation of life; Clinical; Clinical Research; Clinical Trials; Computing Methodologies; Data; Development; Diagnosis; Dose; Edema; Extraprostatic; FDA approved; FOLH1 gene; Feasibility Studies; Fluoroscopy; Future; Generations; Gland; High-Risk Cancer; Imagery; Implant; Individual; Institutional Review Boards; Lead; Malignant Neoplasms; Malignant neoplasm of prostate; Normal tissue morphology; Organ; Outcome; PET/CT scan; PSA screening; Patients; Performance; Phase II Clinical Trials; Physicians; Positioning Attribute; Positron-Emission Tomography; Postoperative Period; Procedures; Prostate; Prostate Cancer therapy; Prostatic; Public Health; Quality of life; Quantitative Evaluations; Radiation; Radiation exposure; Radioactive Seed Implantation; Randomized; Rectum; Screening for Prostate Cancer; Seeds; Software Tools; Source; Structure; System; Techniques; Tissues; Toxic effect; Ultrasonography; Uncertainty; Update; Urethra; Validation; Work; X-Ray Computed Tomography; antigen binding; base; cancer imaging; disorder control; dosimetry; image guided; improved; individual patient; intraoperative imaging; men; mortality; personalized medicine; phase II trial; pre-clinical; randomized trial; reconstruction; response; standard of care; stem; targeted imaging; treatment planning; tumor

PROJECT SUMMARY/ ABSTRACT Prostate cancer remains a worldwide public health issue and cause of mortality, with annual diagnosis and mortality rates exceeding 1.1 billion and 307 million patients, respectively.1 Brachytherapy is widely accepted and utilized in the management of prostate cancer. Due to recent evidence showing improved disease control in patients with potentially lethal cancers using approaches incorporating brachytherapy, its utilization is expected to increase. Successful brachytherapy hinges on adequately dosing prostate while avoiding excessive radiation to adjacent tissues. Well-recognized contributors to poor dosimetry are source positioning errors, poor source visualization and edema, which in aggregate lead to regions of excessive as well as inadequate dose. In response to the recognized need for dynamic visualization of sources and intraoperative dose analysis during the procedure, our work has led to the development of a system of intraoperative ultrasound and fluoroscopy (iRUF) dynamic dose calculation using fluoroscopy-based seed reconstruction and fusion with intraprocedure ultrasound imaging. Following our pilot feasibility trial, we developed an FDA-approved dedicated brachytherapy platform, and have confirmed this technique in a Phase II trial, with outstanding dosimetry on a consistent basis.2,3 Currently, whole-gland treatment is standard in prostate cancer therapy. The need for whole-gland treatment stems from the uncertainty and difficulty in precisely identifying tumor foci within. Unfortunately, such approaches inevitably result in radiation exposure of adjacent critical structures, with potential toxicity and permanent quality of life effects. As long as whole gland therapy is delivered, the ability to limit normal tissue doses remains constrained by their proximity. New advances in PET imaging targeting Prostate Specific Membrane Antigen (PSMA) and second-generation PSMA-binding agents now allow highly specific and sensitive identification of extraprostatic and intraprostatic tumors.4,5,6 Focal therapy using PSMA PET/CT-and dynamic dosimetry-guided seed placement promises to further improve the standard of care in brachytherapy, allowing the physician to precisely tailor the dose to the individual’s tumor. This requires precise tumor imaging combined with dynamic intra-operative localization of the implant in relation to the target volume, as well as surrounding uninvolved prostate and normal anatomy.7,8,9,10 Combining iRUF and PSMA PET/CT would break new ground through addition of precise targeting via purely computational methods. We aim to develop a clinically feasible image-guidance platform for dynamic, quantitative evaluation of partial-gland, focal dosimetry during brachytherapy. The system would allow personalized brachytherapy, achieving excellent cancer control while avoiding unnecessary toxicity for prostate cancer survivors.

项目概要/摘要 前列腺癌仍然是一个世界范围的公共卫生问题和死亡原因，每年都有诊断和治疗 死亡率分别超过 11 亿和 3.07 亿患者。1 近距离放射治疗被广泛接受 并用于前列腺癌的治疗。由于最近的证据表明疾病控制有所改善 在使用近距离放射治疗方法的潜在致命癌症患者中，其利用率是 预计会增加。成功的近距离放射治疗取决于充分剂量的前列腺，同时避免 对邻近组织的过度辐射。公认的导致剂量测定不良的因素是源定位 错误、不良的源可视化和水肿，这些因素总的来说会导致过度和过度的区域 剂量不足。 响应源动态可视化和术中剂量分析的公认需求 在手术过程中，我们的工作导致了术中超声和系统的开发 使用基于荧光透视的种子重建和融合进行荧光透视 (iRUF) 动态剂量计算 术中超声成像。经过试点可行性试验后，我们开发了 FDA 批准的 专用近距离放射治疗平台，并已在 II 期试验中证实了该技术，具有出色的 剂量测定保持一致。2,3 目前，全腺治疗是前列腺癌治疗的标准。需要全腺体 治疗源于精确识别肿瘤病灶的不确定性和困难。不幸的是，这样的 方法不可避免地导致邻近关键结构的辐射暴露，具有潜在的毒性和 对生活质量的永久影响。只要进行全腺体治疗，就能够限制正常组织 剂量仍然受到距离的限制。针对前列腺特异性的 PET 成像新进展 膜抗原 (PSMA) 和第二代 PSMA 结合剂现在可以实现高度特异性和 前列腺外和前列腺内肿瘤的灵敏识别。4,5,6 使用 PSMA PET/CT 进行局部治疗 动态剂量测定引导的粒子放置有望进一步提高近距离放射治疗的护理标准， 允许医生根据个人的肿瘤精确调整剂量。这需要精准的肿瘤 成像结合植入物相对于目标体积的动态术中定位，如 以及周围未受累前列腺和正常解剖结构。7,8,9,10 结合 iRUF 和 PSMA PET/CT 将 通过纯计算方法添加精确定位，开辟新天地。 我们的目标是开发一个临床上可行的图像引导平台，用于动态、定量评估 近距离放射治疗期间的部分腺体、局部剂量测定。该系统将允许个性化近距离放射治疗， 实现出色的癌症控制，同时避免前列腺癌幸存者不必要的毒性。