Metastatic Spine Tumors: Minimally Invasive Fracture Risk Analysis and Treatment - Master

转移性脊柱肿瘤：微创骨折风险分析和治疗 - 硕士

• 批准号: 8963947
• 负责人: Lichun Lu
• 金额: $ 46.93万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8963947
• 关键词: Activities of Daily Living; Address; Affect; Amendment; American; Anterior; Applications Grants; Back; Biocompatible; Biocompatible Materials; Biopsy; Braces-Orthopedic appliances; Cadaver; Caring; Cauda Equina; Clinic; Clinical; Communities; Complex; Consultations; Counseling; Data; Decision Making; Defect; Development; Disseminated Malignant Neoplasm; Dual-Energy X-Ray Absorptiometry; Elements; Endocrinology; Evaluation; Excision; Exercise; Failure; Family; Finite Element Analysis; Fracture; Fumarates; Future; Goals; Grant; Hip Fractures; Home environment; Hospitals; Household; Hydrogels; Image; Implant; Injectable; Injury; Institution; Institutional Review Boards; Laboratories; Left; Length of Stay; Lesion; Life; Link; Lytic; Malignant Neoplasms; Metastatic Lesion; Methodology; Methods; Methylmethacrylate; Minerals; Modeling; Musculoskeletal; Nature; Neoplasm Metastasis; Neurologic; Operative Surgical Procedures; Osteoporosis; Outcome; Outcome Study; Pain; Paralysed; Pathologic; Pathologist; Patient Care; Patients; Physiological; Polymers; Positioning Attribute; Recommendation; Rehabilitation therapy; Rehydrations; Research; Residual state; Rest; Risk; Scanning; Scheme; Services; Societies; Sorting - Cell Movement; Spinal; Spinal Cord; Spinal Fractures; Spinal nerve structure; Structure; Surgical Decompression; System; Techniques; Testing; Time; Tissues; Tube; Tumor Tissue; Validation; Vertebral column; Weight-Bearing state; Work; X-Ray Computed Tomography; accurate diagnosis; base; bone; bone metabolism; caprolactone; clinical practice; college; computerized; copolymer; crosslink; design; experience; good laboratory practice; grandchild; implantable device; improved; indexing; instrumentation; lumbar vertebra bone structure; minimally invasive; novel; oligo(poly(ethylene glycol)fumarate); operation; patient population; poly(propylene fumarate); programs; propylene; public health relevance; reconstitution; reconstruction; scaffold; soft tissue; spinal cord compression; spine bone structure; tumor; user-friendly; vertebra body

 DESCRIPTION (provided by applicant): The identification of cancer metastases to the bony vertebral column obligates the treating clinician to make a surgical decision. Current spinal stability decision-making is empirical, qualitative in nature, and can be inaccurate, even when done by experienced spinal clinicians. The consequences of that decision, however, are significant for the patient whether the recommendation is for surgical or non-surgical treatment. If the spine is deemed unstable and at risk for fracture, then the patient will undergo a major spinal operation, and will often spend much of their remaining life recuperating from it. Conversely, the patient whose spine is deemed stable, and who receives non-surgical treatment, risks fracture and possible paralysis if the stability analysis was incorrect. This research program addresses three critical issues involved in the care of patients with metastatic spine defects. We propose to develop quantitative, reliable, and user-friendly methodologies to predict the fracture risk of vertebrae with metastatic cancer under physiologically relevant loading conditions. We will optimize minimally invasive treatment techniques using novel biomaterials to reconstitute the load bearing capacity of an affected vertebra that has either contained (hole in a bone) or non-contained (a missing segment of a bone) defects. In the first grant cycle, we have successfully developed both a static vertebral structural analysis (VSA) program for non-invasive fracture risk prediction and injectable polymeric implant devices for minimally invasive treatment of vertebrae with contained defects. We have performed initial validation of the program using single cadaveric vertebral bodies tested under compression loads. In this second cycle, we plan to develop and optimize a novel, hydrogel-based, expandable polymer composite treatment system for non-contained vertebral body defects in spines with metastatic lesions (Aim 1). Biocompatible, crosslinked hollow tube scaffolds composed of poly(caprolactone fumarate) (PCLF) and oligo[poly(ethylene glycol) fumarate] (OPF) hydrogel will be fabricated. The dehydrated PCLF/OPF tube can be inserted around the spinal cord or cauda equina into an anterior position within the non-contained vertebral defect. Upon rehydration the polymeric implant will expand back to its pre-determined size. Poly(propylene fumarate) (PPF) or poly(methylmethacrylate) (PMMA) will then be injected through the tube wall to fill the lumen of the hollow tube. In Aim 2, we will test the biomaterial implant systems for both contained (Aim 2a) and non-contained (Aim 2b) metastatic spine lesions in cadavers. Three-level functional spinal units with contained, simulated lytic defects in the middle vertebra, either left untreated, treated with PPF-co-PCL copolymers (the injectable materials previously developed during our first grant cycle), or treated with PMMA will be mechanically tested under both axial compressive loads and flexion bending moments. The results will be used to validate the VSA program under both types of loading conditions. Cadaver spines with a missing segment reconstructed by the novel expandable PCLF/OPF/PPF graft developed in Aim 1 will be tested with concomitant posterior spinal instrumentation under flexion bending moments to accurately model the usual clinical situation in these types of spinal reconstructions. In Aim 3, we will add finite element analysis (FEA), under relevant physiological loading conditions during specific activities of daily living (ADLs) to the VSA program. The two methodologies, static VSA and VSA/FEA, are complementary in nature. The static VSA uses image-based analysis to provide a yes/no surgical decision under resting conditions, while the FEA model analyzes both the vertebral body and the posterior elements under specific ADL loading situations to allow the clinician to counsel her/his patient regarding ADLs that can be performed with a low risk of spinal fracture. Our future plans are to introduce the initial clinica implementation of the spinal VSA/FEA analysis program in two ways. The first method of implementation will be on the metastatic spine patient population in our clinical practices at Mayo Clinic and through our consultant, Dr. Brian Snyder, in the Harvard system of hospitals. We will seek IRB approval at each institution to add VSA/FEA to the evaluation of these patient's metastatic spinal lesions, and then incorporate these data in our discussion with the patients regarding our recommendations for their care. We will study the outcome results of those recommendations, adjust the decision parameters as necessary based on those outcomes, and then extend the analysis to additional institutions via the Musculoskeletal Tumor Society, as Dr. Snyder and we have done in the past with a metastatic hip fracture analysis program. In the second implementation method, we will include the VSA/FEA as an added component to our existing Mayo Clinic osteoporosis external consultation service. In conjunction with our bone metabolism endocrinology colleagues, our laboratory performs quantitative bone histomorphometry on ~50 transiliac bone biopsies per year. We are Good Laboratory Practices (GLP) compliant, Clinical Laboratory Improvement Amendments Act (CLIA) certified, and College of American Pathologists (CAP) certified for this work. We will add the VSA/FEA results to the battery of studies done as part of the osteoporosis evaluation by setting the lesion size to zero, and thus calculating the vertebral strength and stiffness based on the amount and distribution of bone mineral in the same lumbar vertebrae that are used for the patient's DEXA scan.

 描述（通过应用程序提供）：鉴定癌症转移到奖励椎骨柱上义务治疗临床以做出手术决定。当前的脊柱稳定性决策是经验性的，本质上是定性的，即使是由经验丰富的脊柱临床医生完成的，也可能不准确。但是，该决定的后果对患者而言是重要的，无论该建议是针对手术还是非手术治疗的建议。如果脊柱被认为是不稳定的，并且有骨折的风险，那么患者将进行主要的脊柱手术，并且经常将其剩余的大部分寿命从中度过。相反，如果稳定性分析不正确，则视为脊柱被视为稳定并接受非手术治疗的患者可能会骨折和可能的麻痹。该研究计划解决了转移性脊柱缺陷患者护理的三个关键问题。我们建议开发定量，可靠和用户友好的方法，以预测在物理相关的负载条件下转移性癌的椎骨骨折风险。我们将使用新型的生物材料优化微创治疗技术，以重建受影响的椎骨的负载能力，该椎骨包含（骨骼中的孔）或不包含的（骨骼缺失）缺陷。在第一个赠款周期中，我们成功地开发了用于非侵入性断裂风险预测的静态椎骨结构分析（VSA）程序，也开发了可注射的聚合物植入器设备，用于对椎骨的微创处理，并具有包含缺陷的椎骨。我们使用在压缩载荷下测试的单个尸体椎体对程序进行了初始验证。在第二个周期中，我们计划开发和优化一种新型的基于水凝胶的，可扩展的聚合物复合处理系统，以针对具有转移性病变的棘突中的非连接椎体缺陷（AIM 1）。将制造由聚（氟甲酸酯）（PCLF）和寡醇[聚（乙二醇）富马酸酯]（OPF）水凝胶组成的生物相容性的交联空心管支架。可以将脱水的PCLF/OPF管插入脊髓或Cauda Equina周围的椎骨静脉缺陷中的前部位置。补液后，聚合物植入物将扩展到其预定的大小。然后将通过管壁注入聚（PPF）或聚（PPF）或聚（甲基丙烯酸酯）（PMMA），以填充空心管的腔。在AIM 2中，我们将测试尸体中包含（AIM 2A）和非含有（AIM 2B）转移性脊柱病变的生物材料植入系统。具有包含的，模拟的裂解缺陷的三级功能性脊柱单元 中间椎骨未经处理，用PPF-CO-PCL共聚物（以前在我们第一个赠款周期中开发的可注射材料）处理，或者用PMMA处理的是在轴向压缩载荷和屈曲弯曲矩时进行机械测试。结果将用于在两种类型的加载条件下验证VSA程序。在AIM 1中开发的新型可扩展的PCLF/OPF/PPF移植物重构的尸体棘突将在屈曲弯矩下与伴随的后脊柱仪器进行测试，以准确地对这些类型的脊柱重建中的常规临床状况进行建模。在AIM 3中，我们将在“日常生活”（ADLS）在相关的物理负载条件下添加有限元分析（FEA），并将其添加到VSA计划中。这两种方法是静态VSA和VSA/FEA，本质上是完整的。静态VSA使用基于图像的分析在静止条件下提供是/否外科决策，而FEA模型在特定的ADL负载情况下分析了椎体和后部元素，以使临床可以为他/他的患者提供有关脊髓菌群风险低的ADL的咨询。我们未来的计划是通过两种方式介绍脊柱VSA/FEA分析计划的最初临床实施。第一种实施方法将是在我们在梅奥诊所的临床实践中，并通过我们的顾问Brian Snyder博士在哈佛医院的临床实践中。我们将在每个机构中寻求IRB批准，以在评估这些患者的转移性脊柱病变的评估中添加VSA/FEA，然后将这些数据纳入我们与患者有关我们的护理建议的讨论中。我们将研究这些建议的结果，根据这些结果根据需要调整决策参数，然后通过肌肉骨骼肿瘤社会将分析扩展到其他机构，因为Snyder博士和我们过去曾通过转移性髋部骨折分析计划进行。在第二种实施方法中，我们将将VSA/FEA作为我们现有的Mayo Clinic骨质疏松症外部咨询服务的额外组成部分。与我们的骨骼代谢内分泌学同事一起，我们的实验室每年对〜50个跨性骨活检进行定量骨骼组态法。我们是良好的实验室实践（GLP）符合临床实验室改进法案（CLIA）认证的临床实验室改进法案，并获得了这项工作认证的美国病理学家学院（CAP）。我们将通过将病变大小设置为骨质疏松症评估的一部分，将VSA/FEA结果添加到一系列研究中 零，从而根据用于患者DEXA扫描的同一腰椎中骨矿物质的数量和分布来计算椎骨强度和刚度。