Thomas, Lancet Oncol 2010 - Denosumab in Patients with Giant-Cell Tumour of Bone: An Open-Label, Phase 2 Study

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Denosumab in Patients with Giant-Cell Tumour of Bone: An Open-Label, Phase 2 Study

Thomas, Jun, et al.·Lancet Oncol·2010·708 citations·Prospective cohort

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Background

Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT.

Methods

In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1.
The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25.
Study recruitment is closed; patient treatment and follow-up are ongoing.
The study is registered with Clinical Trials.gov, NCT00396279.

Results

Two patients had insufficient histology or radiology data for efficacy assessment.
30 of 35 (86%; 95% CI 70-95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology.
Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4).
Five patients had grade 3-5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related.
Five serious adverse events were reported although none were deemed treatment related.

Conclusions

Further investigation of denosumab as a therapy for GCT is warranted.

Copyright remains with the authors and publisher.

Denosumab in Patients with Giant-Cell Tumour of Bone: An Open-Label, Phase 2 Study.

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Acetabular Defect Classification and Surgical Reconstruction in Revision Arthroplasty. A 6-Year Follow-Up Evaluation.

Paprosky, Lawrence, et al.J Arthroplasty19941,213 citationsRetrospective cohort

Effects of Bracing in Adolescents with Idiopathic Scoliosis.

Weinstein, Dobbs, et al.N Engl J Med20131,160 citationsRCT

Adolescent Idiopathic Scoliosis: A New Classification to Determine Extent of Spinal Arthrodesis.

Lenke, Blanke, et al.J Bone Joint Surg Am20011,720 citationsDiagnostic study

Problems in the Management of Type III (Severe) Open Fractures: A New Classification of Type III Open Fractures.

Gustilo, Williams, et al.J Trauma19842,361 citationsRetrospective cohort

Neer Award 2005: The Grammont Reverse Shoulder Prosthesis: Results in Cuff Tear Arthritis, Fracture Sequelae, and Revision Arthroplasty.

Boileau, Hovorka, et al.J Shoulder Elbow Surg20061,115 citationsProspective cohort

A System for the Surgical Staging of Musculoskeletal Sarcoma.

Enneking, Goodman, et al.Clin Orthop Relat Res19802,112 citationsRetrospective cohort

Fracture Fixation in the Operative Management of Hip Fractures (FAITH): An International, Multicentre, Randomised Controlled Trial.

Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) InvestigatorsLancet2017310 citationsRCT

Fatty Muscle Degeneration in Cuff Ruptures. Pre- and Postoperative Evaluation by CT Scan.

Goutallier, Voisin, et al.Clin Orthop Relat Res19942,669 citationsProspective cohort

Dislocations after Total Hip-Replacement Arthroplasties.

Lewinnek, Zimmerman, et al.J Bone Joint Surg Am19782,549 citationsRetrospective cohort

Morphologic Study of the Glenoid in Primary Glenohumeral Osteoarthritis.

Walch, Khoury, et al.J Arthroplasty19991,142 citationsRetrospective cohort

The Three Column Spine and Its Significance in the Classification of Acute Thoracolumbar Spinal Injuries.

DenisSpine (Phila Pa 1976)19832,566 citationsRetrospective cohort

The Reverse Shoulder Prosthesis for Glenohumeral Arthritis Associated with Severe Rotator Cuff Deficiency. A Minimum Two-Year Follow-Up Study of Sixty Patients.

Frankle, Vasey, et al.J Bone Joint Surg Am2005773 citationsRetrospective cohort

Randomized Trial of Reamed and Unreamed Intramedullary Nailing of Tibial Shaft Fractures.

Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators, Walter, et al.J Bone Joint Surg Am2008445 citationsRCT

A New Classification of Thoracolumbar Injuries: The Importance of Injury Morphology, the Integrity of the Posterior Ligamentous Complex, and Neurologic Status.

Vaccaro, Oner, et al.Spine (Phila Pa 1976)2005866 citationsConsensus statement

A Trial of Wound Irrigation in the Initial Management of Open Fracture Wounds.

FLOW Investigators, Guyatt, et al.N Engl J Med2015347 citationsRCT

Curve Progression in Idiopathic Scoliosis.

Weinstein, PonsetiJ Bone Joint Surg Am1983641 citationsRetrospective cohort

Traumatic Glenohumeral Bone Defects and Their Relationship to Failure of Arthroscopic Bankart Repairs: Significance of the Inverted-Pear Glenoid and the Humeral Engaging Hill-Sachs Lesion.

Burkhart, De BeerArthroscopy20001,884 citationsCase series

The Value of the Tip-Apex Distance in Predicting Failure of Fixation of Peritrochanteric Fractures of the Hip.

Baumgaertner, Keggi, et al.J Bone Joint Surg Am19951,441 citationsRetrospective cohort

Transchondral Fractures (Osteochondritis Dissecans) of the Talus.

Berndt, HartyJ Bone Joint Surg Am1959945 citationsBiomechanical study

Surgical versus Nonsurgical Therapy for Lumbar Spinal Stenosis.

Weinstein, SPORT Investigators, et al.N Engl J Med20081,207 citationsRCT

The Lateral Pillar Classification of Legg-Calvé-Perthes Disease.

Herring, Browne, et al.J Pediatr Orthop1992461 citationsRetrospective cohort

Natural History of Asymptomatic Rotator Cuff Tears: A Longitudinal Analysis of Asymptomatic Tears Detected Sonographically.

Yamaguchi, Middleton, et al.J Shoulder Elbow Surg2001498 citationsRetrospective cohort

The Rotator Crescent and Rotator Cable: An Anatomic Description of the Shoulder's "Suspension Bridge".

Burkhart, Jolson, et al.Arthroscopy1993469 citationsAnatomic study

Posterolateral Rotatory Instability of the Elbow.

O'Driscoll, Morrey, et al.J Bone Joint Surg Am1991997 citationsCase series

Preoperative versus Postoperative Radiotherapy in Soft-Tissue Sarcoma of the Limbs: A Randomised Trial.

O'Sullivan, Zee, et al.Lancet20021,587 citationsRCT

Nonoperative Treatment Compared with Plate Fixation of Displaced Midshaft Clavicular Fractures. A Multicenter, Randomized Clinical Trial.

Canadian Orthopaedic Trauma SocietyJ Bone Joint Surg Am2007804 citationsRCT

Microvasculature of the Human Meniscus.

Arnoczky, WarrenAm J Sports Med19821,227 citationsAnatomic study

Metastatic Disease in Long Bones. A Proposed Scoring System for Diagnosing Impending Pathologic Fractures.

MirelsClin Orthop Relat Res19891,222 citationsRetrospective cohort

Early versus Delayed Decompression for Traumatic Cervical Spinal Cord Injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS).

Fehlings, Rampersaud, et al.PLoS One20121,200 citationsProspective cohort

Three-Dimensional Analysis of the Proximal Part of the Humerus: Relevance to Arthroplasty

Robertson, Yamaguchi, et al.J Bone Joint Surg Am2000255 citationsAnatomic study

Impingement Lesions.

NeerClin Orthop Relat Res19831,827 citationsReview article

Direct Decompressive Surgical Resection in the Treatment of Spinal Cord Compression Caused by Metastatic Cancer: A Randomised Trial.

Patchell, Young, et al.Lancet20052,356 citationsRCT

Injuries Involving the Epiphyseal Plate

Salter, HarrisJ Bone Joint Surg Am19631,737 citationsRetrospective cohort

The Disabled Throwing Shoulder: Spectrum of Pathology Part III: The SICK Scapula, Scapular Dyskinesis, the Kinetic Chain, and Rehabilitation.

Burkhart, Kibler, et al.Arthroscopy2003929 citations

Cuff-Tear Arthropathy.

Neer, Fukuda, et al.J Bone Joint Surg Am1983774 citationsCase series

A System of Staging Musculoskeletal Neoplasms.

EnnekingClin Orthop Relat Res19861,083 citationsReview article

Elbow Instability.

O'DriscollActa Orthop Belg199959 citationsReview article

Effect of Achilles Tendon Lengthening on Neuropathic Plantar Ulcers: A Randomized Clinical Trial

Mueller, Johnson, et al.J Bone Joint Surg Am2003347 citationsRCT

The Management of Acetabular Insufficiency Secondary to Metastatic Malignant Disease

HarringtonJ Bone Joint Surg Am1981303 citationsCase series

Acetabular Anatomy and the Transacetabular Fixation of Screws in Total Hip Arthroplasty

Wasielewski, Rubash, et al.J Bone Joint Surg Am1990290 citationsAnatomic study

Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes: A Prospective Study.

Hewett, Succop, et al.Am J Sports Med20053,495 citationsProspective cohort

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Sirveaux, Molé, et al.J Bone Joint Surg Br20041,598 citationsRetrospective cohort

Hip Morphology Influences the Pattern of Damage to the Acetabular Cartilage: Femoroacetabular Impingement as a Cause of Early Osteoarthritis of the Hip.

Beck, Ganz, et al.J Bone Joint Surg Br20051,955 citationsRetrospective cohort

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Sanders, Walling, et al.Clin Orthop Relat Res1993891 citationsProspective cohort

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Lauge-HansenArch Surg1950830 citationsBiomechanical study

The Natural History of Legg-Calvé-Perthes Disease.

Stulberg, Wallensten, et al.J Bone Joint Surg Am1981810 citationsRetrospective cohort

Reconstruction of the Ulnar Collateral Ligament in Athletes.

Jobe, Lombardo, et al.J Bone Joint Surg Am1986758 citationsCase series

Replacement Arthroplasty for Glenohumeral Osteoarthritis.

NeerJ Bone Joint Surg Am1974598 citationsCase series

Fractures of the Neck of the Talus.

HawkinsJ Bone Joint Surg Am1970556 citationsRetrospective cohort

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CharnleyLancet1961834 citationsCase series

Degenerative Lumbar Spondylolisthesis with Spinal Stenosis. A Prospective Study Comparing Decompression with Decompression and Intertransverse Process Arthrodesis.

Herkowitz, KurzJ Bone Joint Surg Am19911,032 citationsProspective cohort

Limits of Movement in the Human Knee. Effect of Sectioning the Posterior Cruciate Ligament and Posterolateral Structures.

Grood, Noyes, et al.J Bone Joint Surg Am1988674 citationsBiomechanical study

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Ponseti, SmoleyClin Orthop Relat Res1963218 citationsRetrospective cohort

The Outcome and Repair Integrity of Completely Arthroscopically Repaired Large and Massive Rotator Cuff Tears.

Galatz, Yamaguchi, et al.J Bone Joint Surg Am20042,135 citationsCase series

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Pfirrmann, Boos, et al.Spine (Phila Pa 1976)20013,960 citationsDiagnostic study

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NeerJ Bone Joint Surg Am19701,957 citationsRetrospective cohort

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Stiell, Worthington, et al.JAMA20011,283 citationsProspective cohort

The Arterial Vascularization of the Humeral Head. An Anatomical Study.

Gerber, Vinh, et al.J Bone Joint Surg Am1990441 citationsAnatomic study

SLAP Lesions of the Shoulder.

Snyder, Friedman, et al.Arthroscopy19901,264 citationsCase series

Displaced Proximal Humeral Fractures. II. Treatment of Three-Part and Four-Part Displacement.

NeerJ Bone Joint Surg Am19701,283 citationsRetrospective cohort

Functional and Structural Outcome after Arthroscopic Full-Thickness Rotator Cuff Repair: Single-Row versus Dual-Row Fixation

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Rosenberg, Wesley, et al.Ann Surg19821,347 citationsRCT

Anterior Acromioplasty for the Chronic Impingement Syndrome in the Shoulder. 1972.

NeerJ Bone Joint Surg Am1972536 citationsCase series

Abnormal Magnetic-Resonance Scans of the Lumbar Spine in Asymptomatic Subjects. A Prospective Investigation.

Boden, Wiesel, et al.J Bone Joint Surg Am1990668 citationsProspective cohort

Hip Arthroscopy versus Best Conservative Care for the Treatment of Femoroacetabular Impingement Syndrome (UK FASHIoN): A Multicentre Randomised Controlled Trial.

Griffin, FASHIoN Study Group, et al.Lancet2018542 citationsRCT

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Insall, Burstein, et al.J Bone Joint Surg Am1982470 citationsRetrospective cohort

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Brooker, Riley, et al.J Bone Joint Surg Am19732,880 citationsRetrospective cohort

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Dejour, Guier, et al.Knee Surg Sports Traumatol Arthrosc19941,987 citationsCase-control study

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Morrey, Chao, et al.J Bone Joint Surg Am19811,380 citationsBiomechanical study

The Disabled Throwing Shoulder: Spectrum of Pathology Part I: Pathoanatomy and Biomechanics.

Burkhart, Kibler, et al.Arthroscopy20031,304 citationsReview article

Grammont Reverse Prosthesis: Design, Rationale, and Biomechanics.

Boileau, Balg, et al.J Shoulder Elbow Surg20051,232 citationsReview article

Fractures of the Acetabulum: Classification and Surgical Approaches for Open Reduction. Preliminary Report.

Judet, Letournel, et al.J Bone Joint Surg Am1964980 citationsCase series

Inferior Capsular Shift for Involuntary Inferior and Multidirectional Instability of the Shoulder. A Preliminary Report.

Neer, FosterJ Bone Joint Surg Am1980934 citationsCase series

The Impact of Positive Sagittal Balance in Adult Spinal Deformity.

Glassman, Schwab, et al.Spine (Phila Pa 1976)20051,878 citationsRetrospective cohort

An Analysis of Outcomes of Reconstruction or Amputation after Leg-Threatening Injuries.

Bosse, Castillo, et al.N Engl J Med2002901 citationsProspective cohort

Normal and Abnormal Motion of the Shoulder.

Poppen, WalkerJ Bone Joint Surg Am1976886 citationsCase-control study

Posterior C1-C2 Fusion with Polyaxial Screw and Rod Fixation.

Harms, MelcherSpine (Phila Pa 1976)20011,528 citationsCase series

A Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures.

Kallmes, Jarvik, et al.N Engl J Med20091,422 citationsRCT

A Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures.

Buchbinder, Murphy, et al.N Engl J Med20091,416 citationsRCT

Validity of a Set of Clinical Criteria to Rule Out Injury to the Cervical Spine in Patients with Blunt Trauma. National Emergency X-Radiography Utilization Study Group.

Hoffman, Zucker, et al.N Engl J Med20001,302 citationsProspective cohort

Total Hip Arthroplasty or Hemiarthroplasty for Hip Fracture

HEALTH Investigators, Devereaux, et al.N Engl J Med2019507 citationsRCT

A Classification for Congenital Limb Malformations.

SwansonJ Hand Surg Am1976429 citationsReview article

Treatment of Grade IV Fracture-Dislocation of the Hip.

PipkinJ Bone Joint Surg Am1957445 citationsCase series

Compression-Plate Fixation in Acute Diaphyseal Fractures of the Radius and Ulna

Anderson, Park, et al.J Bone Joint Surg Am1975416 citationsCase series

Legg-Calve-Perthes Disease. Part II: Prospective Multicenter Study of the Effect of Treatment on Outcome.

Herring, Browne, et al.J Bone Joint Surg Am2004143 citationsProspective cohort

The Role of the Scapula in Athletic Shoulder Function.

KiblerAm J Sports Med19981,240 citationsReview article

The SLAC Wrist: Scapholunate Advanced Collapse Pattern of Degenerative Arthritis.

Watson, BalletJ Hand Surg Am19841,138 citationsRetrospective cohort

Classification and an Algorithmic Approach to the Reconstruction of Femoral Deficiency in Revision Total Hip Arthroplasty.

Valle, PaproskyJ Bone Joint Surg Am2003199 citationsRetrospective cohort

The Tibial Plateau Fracture. The Toronto Experience 1968--1975.

Schatzker, Bruce, et al.Clin Orthop Relat Res19791,029 citationsRetrospective cohort

Surgical Dislocation of the Adult Hip a Technique with Full Access to the Femoral Head and Acetabulum without the Risk of Avascular Necrosis.

Ganz, Berlemann, et al.J Bone Joint Surg Br20011,367 citationsCase series

Predictors of Humeral Head Ischemia after Intracapsular Fracture of the Proximal Humerus.

Hertel, Leunig, et al.J Shoulder Elbow Surg2004837 citationsProspective cohort

Early versus Delayed Stabilization of Femoral Fractures. A Prospective Randomized Study.

Bone, Scheinberg, et al.J Bone Joint Surg Am1989795 citationsRCT

Acetabulum Fractures: Classification and Management.

LetournelClin Orthop Relat Res1980715 citationsRetrospective cohort

A Novel Classification System for Spinal Instability in Neoplastic Disease: An Evidence-Based Approach and Expert Consensus from the Spine Oncology Study Group.

Fisher, Fourney, et al.Spine (Phila Pa 1976)20101,224 citationsConsensus statement

Surgical vs. Nonsurgical Treatment of Adults with Displaced Fractures of the Proximal Humerus: The PROFHER Randomized Clinical Trial.

Rangan, PROFHER Trial Collaborators, et al.JAMA2015540 citationsRCT

Lumbar Disc Herniation. A Controlled, Prospective Study with Ten Years of Observation.

WeberSpine (Phila Pa 1976)19831,149 citationsRCT

Surgical vs. Nonoperative Treatment for Lumbar Disk Herniation. The Spine Patient Outcomes Research Trial (SPORT): A Randomized Trial

Weinstein, Deyo, et al.JAMA20061,086 citationsRCT

Health and Function of Patients with Untreated Idiopathic Scoliosis: A 50-Year Natural History Study.

Weinstein, Ponseti, et al.JAMA2003755 citationsProspective cohort

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Denosumab in Patients with Giant-Cell Tumour of Bone: An Open-Label, Phase 2 Study

Thomas, Jun, et al.·Lancet Oncol·2010·708 citations·Prospective cohort

|

Background

Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT.

Methods

In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1.
The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25.
Study recruitment is closed; patient treatment and follow-up are ongoing.
The study is registered with Clinical Trials.gov, NCT00396279.

Results

Two patients had insufficient histology or radiology data for efficacy assessment.
30 of 35 (86%; 95% CI 70-95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology.
Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4).
Five patients had grade 3-5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related.
Five serious adverse events were reported although none were deemed treatment related.

Conclusions

Further investigation of denosumab as a therapy for GCT is warranted.

Copyright remains with the authors and publisher.

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