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（由申请方提供）：确定癌症转移至骨性脊柱后，治疗临床医生必须做出手术决定。目前的脊柱稳定性决策是经验性的、定性的，并且可能是不准确的，即使是由经验丰富的脊柱临床医生做出的。然而，无论建议手术还是非手术治疗，该决定的后果对患者都很重要。如果脊柱被认为是不稳定的，有骨折的风险，那么病人将接受一个大的脊柱手术，并且通常会花大部分的时间来恢复。相反，如果脊柱被认为是稳定的，并且接受非手术治疗的病人，如果稳定性分析不正确，则有骨折和可能瘫痪的风险。这项研究计划涉及转移性脊柱缺损患者的护理中的三个关键问题。我们建议开发定量的，可靠的，用户友好的方法来预测骨折的风险与转移性癌症的椎骨在生理相关的负荷条件。我们将使用新型生物材料优化微创治疗技术，以重建受影响椎骨的承载能力，该椎骨具有包含（骨中的孔）或非包含（骨缺失段）缺陷。在第一个资助周期中，我们成功开发了用于非侵入性骨折风险预测的静态椎骨结构分析（VSA）程序和用于微创治疗包含缺陷的椎骨的可注射聚合物植入物器械。我们已经使用在压缩载荷下测试的单个尸体椎体对该程序进行了初步确认。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、可膨胀的聚合物复合材料治疗系统，用于脊柱转移性病变中的非包容性椎体缺损（目标1）。将制备由聚（富马酸己内酯）（PCLF）和寡聚[聚（乙二醇）富马酸酯]（OPF）水凝胶组成的生物相容性交联中空管支架。脱水的PCLF/OPF管可以围绕脊髓或马尾插入到非包容性椎体缺损内的前部位置。在再水化时，聚合物植入物将膨胀回到其预定尺寸。然后通过管壁注入聚富马酸丙二醇酯（PPF）或聚甲基丙烯酸甲酯（PMMA），以填充中空管的管腔。在目标2中，我们将测试生物材料植入物系统在尸体中的包容性（目标2a）和非包容性（目标2b）转移性脊柱病变。三节段功能性脊柱单元与包含的，模拟溶解性缺损， 将在轴向压缩载荷和屈曲弯矩下对未处理、用PPF-共-PCL共聚物（在我们的第一个资助周期期间先前开发的可注射材料）处理或用PMMA处理的中间椎骨进行机械测试。结果将用于验证VSA程序在两种类型的负载条件下。将在屈曲弯矩下对目标1中开发的新型可膨胀PCLF/OPF/PPF移植物重建缺失节段的尸体脊柱进行伴随后路脊柱内固定测试，以准确模拟这些类型脊柱重建的常见临床情况。在目标3中，我们将在VSA程序中添加特定日常生活活动（ADL）期间相关生理负载条件下的有限元分析（FEA）。静态VSA和VSA/FEA这两种方法在本质上是互补的。静态VSA使用基于图像的分析，在静息条件下提供是/否手术决策，而FEA模型在特定ADL载荷情况下分析椎体和后部元件，以允许临床医生就可在脊柱骨折低风险下进行的ADL向患者提供咨询。我们未来的计划是以两种方式引入脊柱VSA/FEA分析程序的初始临床实施。第一种实施方法将在我们马约诊所的临床实践中对脊柱转移患者人群进行，并通过我们的顾问Brian Snyder博士在哈佛医院系统中进行。我们将在每家机构寻求IRB批准，以将VSA/FEA添加到这些患者转移性脊柱病变的评价中，然后将这些数据纳入我们与患者讨论的护理建议中。我们将研究这些建议的结果，根据这些结果调整必要的决策参数，然后通过肌肉骨骼肿瘤协会将分析扩展到其他机构，就像Snyder博士和我们过去在转移性髋部骨折分析项目中所做的那样。在第二种实施方法中，我们将VSA/FEA作为现有马约诊所骨质疏松症外部咨询服务的附加组件。与我们的骨代谢内分泌学同事一起，我们的实验室每年对约50例经髂骨骨活检进行定量骨组织形态测定。我们符合药物非临床研究质量管理规范（GLP），临床实验室改进修正法案（CLIA）认证，美国病理学家学会（CAP）认证。我们将通过将病变尺寸设置为 零，并因此基于用于患者的DEXA扫描的相同腰椎中的骨矿物质的量和分布来计算椎骨强度和刚度。