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.

项目总结/摘要 前列腺癌仍然是世界范围内的公共卫生问题和死亡原因，每年诊断和治疗前列腺癌。 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。由于最近的证据显示疾病控制有所改善 在使用结合近距离放射治疗的方法的具有潜在致命性癌症的患者中， 预计将增加。成功的近距离放射治疗取决于足够的前列腺剂量，同时避免 对邻近组织的过度辐射。公认的不良剂量测定的贡献者是源定位 错误，不良的源可视化和水肿，这在一起导致过度的区域，以及 剂量不足。 为了响应公认的对源的动态可视化和术中剂量分析的需求， 在手术过程中，我们的工作导致了术中超声系统的发展， 使用基于荧光透视的种子重建和融合的荧光透视（iMRI）动态剂量计算 术中超声成像。在我们的试点可行性试验之后，我们开发了一种FDA批准的 专门的近距离放射治疗平台，并在II期试验中证实了这种技术， 在一致的基础上进行剂量测定。 目前，全腺体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。可惜这样 这些方法不可避免地会导致邻近关键结构的辐射暴露，具有潜在的毒性， 永久性生活质量影响。只要整个腺体治疗是交付，限制正常组织的能力， 剂量仍然受到其接近程度的限制。靶向前列腺特异性PET成像的新进展 膜抗原（PSMA）和第二代PSMA结合剂现在可以高度特异性和 敏感地识别前列腺外和前列腺内肿瘤。4，5，6使用PSMA PET/CT进行局部治疗， 动态剂量测定引导的种子放置有望进一步提高近距离放射治疗中的护理标准， 允许医生精确地根据个体的肿瘤调整剂量。这需要精确的肿瘤 与植入物相对于靶体积的动态术中定位相结合的成像， 以及周围未受累的前列腺和正常解剖结构。7，8，9，10结合iMRI和PSMA PET/CT将 通过纯粹的计算方法增加精确的目标定位，开辟了新的领域。 我们的目标是开发一种临床可行的图像引导平台，用于动态，定量评价 局部腺体，近距离放射治疗过程中的局部剂量测定。该系统将允许个性化的近距离放射治疗， 从而实现极好的癌症控制，同时避免对前列腺癌幸存者的不必要的毒性。