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

Project: Research project

Project Details


? 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.
Effective start/end date4/1/086/30/21


  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $423,592.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $469,251.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $414,949.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $4,446,346.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $476,926.00


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.