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Ph.D. Og Speciale UNIVERSITY O F COPENHAGEN FACULTY OF HEALTH AN D MEDICAL SCIENCES PhD Thesis Christina Holm Surgical treatment of bone sarcomas and aggressive benign bone tumors. Implant survival, limb survival and adaptive periprosthetic bone remodeling after limb sparing surgery and reconstruction with tumor prostheses and development and comparison of one-year survival prediction models in patients with bone sarcomas Supervisor: Michael Mørk Petersen, MD, DMSc, Professor This thesis has been submitted to the Graduate School of Health and Medical Sciences, University of Copenhagen: February 14, 2020 Institution: Rigshospitalet, University of Copenhagen, Denmark Department: Department of Orthopaedic surgery Musculoskeletal Tumor Section, Rigshospitalet, University of Copenhagen, Denmark Author Christina Holm, MD Title and subtitle: Surgical treatment of bone sarcomas and aggressive benign bone tumors. Implant survival, limb survival and adaptive periprosthetic bone remodeling after limb sparing surgery and reconstruction with tumor prostheses and development and comparison of one-year survival prediction models in patients with bone sarcomas. Principal supervisor Michael Mørk Petersen, MD, DMSc, Professor, Department of Orthopedic surgery, Rigshospitalet, University of Copenhagen, Denmark Principal Co-supervisor Anders Odgaard, MD, DMSc, Professor Department of Orthopedic surgery, Gentofte Hospital University of Copenhagen, Denmark Co-Supervisor Michala Skovlund Sørensen, MD, PhD Assessment committee Chair Jes Bruun Laurtizen, MD, DMSc, Professor Department of Orthopedic surgery, Bispebjerg Hospital University of Copenhagen, Denmark Danish assessor: Peter Holmberg, MD, DMSc, Department of Orthopedic surgery, Aarhus University Hospital, Denmark International assessor: Minna Laitinen, Associate professor, PhD Helsinki University Hospital Bone Tumour Unit, Department of Orthopedics and Traumatology Finland 2 Table of contents AKNOWLEDGEMENTS ...................................................................................................... 6 PREFACE ............................................................................................................................ 8 LIST OF PAPERS ............................................................................................................... 9 SELECTED ABBREVIATIONS ......................................................................................... 10 ENGLISH SUMMARY ....................................................................................................... 11 DANISH SUMMARY.......................................................................................................... 13 BACKGROUND ................................................................................................................ 15 SARCOMAS .................................................................................................................................................... 15 Epidemiology and etiology .......................................................................................................................... 15 Bone sarcomas .............................................................................................................................................. 16 DIAGNOSTIC PROCESS .................................................................................................. 17 Clinical presentation .................................................................................................................................... 17 Diagnostic imaging ...................................................................................................................................... 17 Tumor grading ............................................................................................................................................. 20 TREATMENT ..................................................................................................................... 21 From amputation to limb sparing surgery .................................................................................................. 21 Limb sparring surgery................................................................................................................................... 22 The implant evolution .................................................................................................................................... 23 Moving towards personalized evidence-based treatment ......................................................................... 25 OBJECTIVES .................................................................................................................... 27 Aims and hypotheses .................................................................................................................................... 27 MATERIAL AND METHODS ............................................................................................. 29 Overall study design ..................................................................................................................................... 29 Data sources .................................................................................................................................................. 30 3 Patient inclusion ............................................................................................................................................ 31 Study I ......................................................................................................................................................... 31 Study II ........................................................................................................................................................ 31 Study III ....................................................................................................................................................... 33 Study IV ....................................................................................................................................................... 35 Outcomes and measurements ..................................................................................................................... 37 Study I ......................................................................................................................................................... 37 Study II ........................................................................................................................................................ 37 Study III ....................................................................................................................................................... 37 Study IV ....................................................................................................................................................... 39 Clinical outcome ............................................................................................................................................ 39 Statistical considerations ............................................................................................................................. 40 Study I ......................................................................................................................................................... 40 Study II ........................................................................................................................................................ 40 Study III ....................................................................................................................................................... 41 Study IV ....................................................................................................................................................... 42 ETHICAL APPROVALS .................................................................................................... 44 SUMMARY OF STUDY RESULTS.................................................................................... 45 Study I ......................................................................................................................................................... 45 Study II ........................................................................................................................................................ 47 Study III ....................................................................................................................................................... 52 Study IV ....................................................................................................................................................... 55 DISCUSSION .................................................................................................................... 59 Methodological considerations .................................................................................................................... 59 General considerations ............................................................................................................................... 59 Confounding ................................................................................................................................................ 61 Bias .............................................................................................................................................................. 62 Limitations
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