This 2021 narrative review by Gill and Gorlick surveys the treatment landscape of osteosarcoma — the most common primary bone malignancy in children and young adults. It asks why survival has stagnated for four decades and what molecular, immunologic, and clinical trial innovations may finally change outcomes. The review covers current MAP chemotherapy, molecular subclassification, preclinical models, targeted agents, and immune-based strategies.
A young patient with osteosarcoma progressing through MAP chemotherapy faces a median EFS of 4 months and a 2-year EFS of 12% — numbers that have been unchanged across decades of phase II trials.
Those numbers are not just prognostic. They are the foundation of how new agents are tested in this disease. When you see a trial offering enrollment to a relapsed osteosarcoma patient, know that the 40% disease control rate at 4 months threshold is what separates an active agent from noise in this population.
For the management of refractory disease, single-agent checkpoint inhibition is not a rational choice. Pembrolizumab and nivolumab have both failed convincingly. The active investigational paths are ADCs targeting B7-H3, GPNMB, or LRRC15 (expressed in >91% of tumors), or CAR T cell strategies, particularly for HER2-positive disease where early CR data exist.
The authors note that novel agents will likely need non-overlapping toxicity profiles to be safely combined with the high-dose cytotoxic regimens currently used. This is why TKIs are being explored as maintenance therapy rather than concurrent additions to MAP.
Advancing Therapy for Osteosarcoma
Radiological Assessment of Osteo-Arthrosis.
Mesenchymal Stem Cells.
Traumatic Arthritis of the Hip after Dislocation and Acetabular Fractures: Treatment by Mold Arthroplasty. an End-Result Study Using a New Method of Result Evaluation.
Bone: Formation by Autoinduction.
Treatment of Deep Cartilage Defects in the Knee with Autologous Chondrocyte Transplantation.
Interrater Reliability of a Modified Ashworth Scale of Muscle Spasticity
Osteoclast Differentiation Factor Is a Ligand for Osteoprotegerin/osteoclastogenesis-Inhibitory Factor and Is Identical to Trance/rankl.
Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis. Vigor Study Group.
Magnetic Resonance Classification of Lumbar Intervertebral Disc Degeneration.
Novel Regulators of Bone Formation: Molecular Clones and Activities.
The Diagnosis of Osteoporosis.
"modes of Failure" of Cemented Stem-Type Femoral Components: a Radiographic Analysis of Loosening.
Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes: a Prospective Study.
Femoroacetabular Impingement: a Cause for Osteoarthritis of the Hip.
Prevention of Infection in the Treatment of One Thousand and Twenty-Five Open Fractures of Long Bones: Retrospective and Prospective Analyses.
The Variation in Isometric Tension with Sarcomere Length in Vertebrate Muscle Fibres.
Osteoarthritis: a Disease of the Joint as an Organ.
Radiological Demarcation of Cemented Sockets in Total Hip Replacement.
Ectopic Ossification Following Total Hip Replacement. Incidence and a Method of Classification.
The Operation of the Century: Total Hip Replacement.
Fatty Muscle Degeneration in Cuff Ruptures. Pre- and Postoperative Evaluation by CT Scan.
Osseointegrated Titanium Implants. Requirements for Ensuring a Long-Lasting, Direct Bone-To-Implant Anchorage in Man.
The Etiology of Chondromalacia Patellae.
Fracture and Dislocation Classification Compendium-2018.
The Three Column Spine and Its Significance in the Classification of Acute Thoracolumbar Spinal Injuries.
Dislocations after Total Hip-Replacement Arthroplasties.
Patient Satisfaction after Total Knee Arthroplasty: Who Is Satisfied and Who Is Not?
Problems in the Management of Type III (severe) Open Fractures: a New Classification of Type III Open Fractures.
The Value of Postural Reduction in the Initial Management of Closed Injuries of the Spine with Paraplegia and Tetraplegia. I.
Vacuum-Assisted Closure: a New Method for Wound Control and Treatment: Animal Studies and Basic Foundation.
A System for the Functional Evaluation of Reconstructive Procedures after Surgical Treatment of Tumors of the Musculoskeletal System.
A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee
The Stabilizing System of the Spine. Part I. Function, Dysfunction, Adaptation, and Enhancement.
The Outcome and Repair Integrity of Completely Arthroscopically Repaired Large and Massive Rotator Cuff Tears.
The Tension-Stress Effect on the Genesis and Growth of Tissues. Part I. the Influence of Stability of Fixation and Soft-Tissue Preservation.
A System for the Surgical Staging of Musculoskeletal Sarcoma.
A Comprehensive Classification of Thoracic and Lumbar InjuriesCitation only
Effect of the Tyrosine Kinase Inhibitor Sti571 in a Patient with a Metastatic Gastrointestinal Stromal TumorCitation only
Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture.
Factors of Patellar Instability: an Anatomic Radiographic Study.
Displaced Proximal Humeral Fractures. I. Classification and Evaluation.
Hip Morphology Influences the Pattern of Damage to the Acetabular Cartilage: Femoroacetabular Impingement as a Cause of Early Osteoarthritis of the Hip.
Porosity of 3D Biomaterial Scaffolds and Osteogenesis.
A Report: the Definition and Classification of Cerebral Palsy April 2006.
Clinician's Guide to Prevention and Treatment of Osteoporosis.
Prevention of Venous ThromboembolismCitation only
The Development of Assessment of Spondyloarthritis International Society Classification Criteria for Axial Spondyloarthritis (part II): Validation and Final SelectionCitation only
Radiation Exposure from CT Scans in Childhood and Subsequent Risk of Leukaemia and Brain Tumours: a Retrospective Cohort Study.
Epidemiology of Adult Fractures: a Review.
Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017.
Osteoblastic Cells Regulate the Haematopoietic Stem Cell Niche.
A Joint Coordinate System for the Clinical Description of Three-Dimensional Motions: Application to the Knee.
Consensus Statement on Concussion in Sport-The 5th International Conference on Concussion in Sport Held in Berlin, October 2016.
Oarsi Guidelines for the Non-Surgical Management of Knee Osteoarthritis.
Estimating the Prevalence of Limb Loss in the United States: 2005 to 2050.
Metastasis to Bone: Causes, Consequences and Therapeutic Opportunities.
Role of Proinflammatory Cytokines in the Pathophysiology of Osteoarthritis.
The Basic Science of Articular Cartilage: Structure, Composition, and Function.
Osteoporosis: Now and the Future.
Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity.
Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs. a 1:1:2 Ratio and Mortality in Patients with Severe Trauma: the Proppr Randomized Clinical Trial
Direct Decompressive Surgical Resection in the Treatment of Spinal Cord Compression Caused by Metastatic Cancer: a Randomised Trial.
Fracture and Dislocation Classification Compendium - 2007: Orthopaedic Trauma Association Classification, Database and Outcomes Committee.
Peek Biomaterials in Trauma, Orthopedic, and Spinal Implants.
Effect of Calcium and Vitamin D Supplementation on Bone Density in Men and Women 65 Years of Age or OlderCitation only
The Long-Term Consequence of Anterior Cruciate Ligament and Meniscus Injuries: Osteoarthritis.
Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America.
The Amazing Osteocyte.
Osteosarcoma Incidence and Survival Rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program.
Projected Volume of Primary Total Joint Arthroplasty in the U.s., 2014 to 2030.
The 2018 Definition of Periprosthetic Hip and Knee Infection: an Evidence-Based and Validated Criteria.
Bone Quality--The Material and Structural Basis of Bone Strength and Fragility.
Prevalence of Muscular Dystrophies: a Systematic Literature Review.
Mechanisms of Bone Metastasis.
The Compressive Behavior of Bone as a Two-Phase Porous Structure.
Metastatic Bone Disease: Clinical Features, Pathophysiology and Treatment Strategies.
Diagnosis and Treatment of Hip and Knee Osteoarthritis
Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis.
Opgl Is a Key Regulator of Osteoclastogenesis, Lymphocyte Development and Lymph-Node Organogenesis.
Osteoarthritis: New Insights. Part 1: the Disease and Its Risk Factors.
Morbidity at Bone Graft Donor Sites.
Articular Cartilage Repair: Basic Science and Clinical Progress. a Review of the Current Status and Prospects.
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors.
Guidelines for the Process of Cross-Cultural Adaptation of Self-Report MeasuresCitation only
Assessment of Coma and Impaired Consciousness. a Practical Scale.
Development and Reliability of a System to Classify Gross Motor Function in Children with Cerebral Palsy
Validation Study of Womac: a Health Status Instrument for Measuring Clinically Important Patient Relevant Outcomes to Antirheumatic Drug Therapy in Patients with Osteoarthritis of the Hip or Knee.
Projections of Primary and Revision Hip and Knee Arthroplasty in the United States from 2005 to 2030.
The Oswestry Disability Index.
A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population.
A Clinical Method of Functional Assessment of the Shoulder.
Rating Systems in the Evaluation of Knee Ligament Injuries.
Sf-36 Health Survey UpdateCitation only
Rationale of the Knee Society Clinical Rating System.
Knee Injury and Osteoarthritis Outcome Score (koos)--Development of a Self-Administered Outcome Measure.
Evaluation of Knee Ligament Surgery Results with Special Emphasis on Use of a Scoring Scale.
Development and Validation of the International Knee Documentation Committee Subjective Knee Form.
Delirium in Older Persons.Citation only
Calcium Phosphate Ceramics as Hard Tissue Prosthetics.
The Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System.
This 2021 narrative review by Gill and Gorlick surveys the treatment landscape of osteosarcoma — the most common primary bone malignancy in children and young adults. It asks why survival has stagnated for four decades and what molecular, immunologic, and clinical trial innovations may finally change outcomes. The review covers current MAP chemotherapy, molecular subclassification, preclinical models, targeted agents, and immune-based strategies.
A young patient with osteosarcoma progressing through MAP chemotherapy faces a median EFS of 4 months and a 2-year EFS of 12% — numbers that have been unchanged across decades of phase II trials.
Those numbers are not just prognostic. They are the foundation of how new agents are tested in this disease. When you see a trial offering enrollment to a relapsed osteosarcoma patient, know that the 40% disease control rate at 4 months threshold is what separates an active agent from noise in this population.
For the management of refractory disease, single-agent checkpoint inhibition is not a rational choice. Pembrolizumab and nivolumab have both failed convincingly. The active investigational paths are ADCs targeting B7-H3, GPNMB, or LRRC15 (expressed in >91% of tumors), or CAR T cell strategies, particularly for HER2-positive disease where early CR data exist.
The authors note that novel agents will likely need non-overlapping toxicity profiles to be safely combined with the high-dose cytotoxic regimens currently used. This is why TKIs are being explored as maintenance therapy rather than concurrent additions to MAP.