CURRENT ADVANCES IN OSTEOSARCOMA clinical perspectives.

Preface
	Osteosarcoma: The State of Affairs Dictates a Change in Clinical Practice and Clinical Trial Design
Contents
Contributors
1: Adjuvant and Neoadjuvant Chemotherapy for Osteosarcoma: A Historical Perspective
	History
	References
Part I: Surgical Considerations and Outcomes
	2: Limb Salvage and Reconstruction Options in Osteosarcoma
		Introduction
		Types of Reconstruction
		Endoprosthetic Failure Classification
		Anatomic Locations
			Proximal Femur
			Femoral Diaphysis
			Distal Femur
			Case Example: Distal Femur
			Proximal Tibia
			Case Example: Proximal Tibia
			Distal Tibia
			Proximal Humerus
			Case Example: Proximal Humerus
			Distal Humerus
			Forearm
				Case Example: Forearm
		Skeletally Immature Patients
			Case Example: Expandable Prosthesis
			Case Example: Expandable Prosthesis
			Case Example: Intercalary Graft
		Conclusion
		References
	3: Advances in the Functional Assessment of Patients with Sarcoma
		Introduction
		Quality of Life Measures
		HRQL Measures
			TESS
			MSTS
			SF-36
			SF-6D
			EQ-5D
			PROMIS
		Objective Functional Assessment
			Metabolic and Gait Analysis
			Real-World Functional Assessment
		Real-Time, Real-World Monitoring
		Conclusion
		References
Part II: Novel Therapeutic Approaches Based on Biology
	4: Radiopharmaceuticals for Treatment of Osteosarcoma
		Introduction
		Samarium
		Radium
		Another Radiopharmaceutical for Osteosarcoma: CLR 131
		Patient Selection for Radiopharmaceuticals for Osteosarcoma: Practical Considerations
		Summary and Obtaining Access to Radiopharmaceuticals for Osteosarcoma
		References
	5: HER2-Targeted Therapy in Osteosarcoma
		Introduction
		HER2 as an Oncogene in Osteosarcoma
			HER2 Biology
			HER2 in Osteosarcoma Cell Lines
			HER2 Is a Negative Prognostic Indicator in Osteosarcoma
			HER2 Is Not Prognostic in Osteosarcoma
			HER2 Is a Positive Prognostic Indicator in Osteosarcoma
			Summary of HER2 Expression Studies
		HER2 Targeted Therapies in Osteosarcoma
			HER2 Directed Monoclonal Antibodies
			HER2-Specific Chimeric Antigen Receptor (CAR)-Modified T Cells
			Trastuzumab Deruxtecan (DS-8201)
		Targeting Surface Proteins
		Conclusion
		References
	6: Aerosolized Chemotherapy for Osteosarcoma
		Introduction
		Advantages and Potential Limitations of Aerosolized Chemotherapy
		Preclinical Studies
		Clinical Studies
		Drug Administration
		Safety Considerations
		Summary and Potential Implications
		References
	7: The Histone Deacetylase Inhibitor Entinostat/Syndax 275 in Osteosarcoma
		Introduction
		Fas and the Fas Signaling Pathway
		Fas Expression and Its Role in OS Lung Metastasis Formation
		Gemcitabine and Its Effect on Osteosarcoma
		Histone Deacetylase (HDAC) Inhibitors
		Entinostat/Syndax-275 and Its Effect on Osteosarcoma
		HDAC Effect on the Fas/FasL Apoptotic Pathway
		Gemcitabine and Entinostat/Syndax-275 as Potential Salvage Regimen for Osteosarcoma Lung Metastasis
		References
	8: Relapsed Osteosarcoma Trial Concepts to Match the Complexity of the Disease
		Relapsed Osteosarcoma
		Past Relapsed Trials and a Proposed Efficacy Bars
		Current Landscape of Clinical Trials in OS
		Clinical Trial Participation
		Next Steps: Trial Designs and Efforts Toward Improving Outcomes
		References
	9: Using Liquid Biopsy in the Treatment of Patient with OS
		The Emerging Field of Liquid Biopsy in Cancer
		Liquid Biopsy Technologies and Their Adaptation to Osteosarcoma
			ctDNA
			Circulating Tumor Cells
			miRNA
		Liquid Biopsy Applications in Cancer and Osteosarcoma
			Early Detection and Diagnosis
			Improving Risk Stratification of Newly Diagnosed Patients
			Monitoring Response to Therapy and Detecting Relapse
			Understanding Tumor Heterogeneity and Evolution
		The Path to Clinical Implementation
		Summary
		References
Part III: Novel Immunotherapeutic Approaches
	10: Genetically Modified T-Cell Therapy for Osteosarcoma: Into the Roaring 2020s
		Introduction
		T-Cell Therapy Targets for Osteosarcoma
		Genetic Approaches to Render T Cells Specific for Osteosarcoma
			α/β TCR Modified T Cells
			CAR-Modified T Cells
		Genetic Approaches to Enhance the Effector Function of Osteosarcoma-Specific T Cells
			Enhancing T-Cell Expansion and Persistence In Vivo
			Genetic Modifications to Overcome Tumor-Mediated Immunosuppression
			Genetic Modification of T Cells to Improve Homing to Tumor Sites
			Improving Safety of T-Cell Therapy
			Combinatorial T-Cell Therapy
		Conclusions
		References
	11: Muramyl Tripeptide-Phosphatidyl Ethanolamine Encapsulated in Liposomes (L-MTP-PE) in the Treatment of Osteosarcoma
		Introduction
		Background
		Clinical Trials
		Randomized Phase III Trial
		Phase III Randomized Trial for Patients with Metastatic Disease at Initial Presentation
		Compassionate Access Trial
		Regulatory Status of L-MTP-PE
		References
	12: Natural Killer Cell Immunotherapy for Osteosarcoma
		Brief Overview of NK Cell Biology
			Activating and Inhibitory Receptors
			Mechanisms of NK Cell-Mediated Killing
		Evidence for NK Cell Activity in Osteosarcoma
			NK Cell Function in Patients with Osteosarcoma
			Expression by Osteosarcoma of Ligands Recognized by NK Cells
			Mechanisms of Killing
			Mechanisms of Immune Escape
		Indirect Activation of NK Cell Function
			Monoclonal Antibodies
			Cytokines
			Chemotherapy
			Immunomodulators
		NK Cell Adoptive Immunotherapy
			Clinical NK Cell Sources and Trials
			Future Approaches
		References
	13: Nanocapsule Delivery of IL-12
		Interleukin-12 Immunotherapy: The Past, Present and Future
			Why IL-12?
			The Past and Present (1994–2019)
			The Future
		Production of IL-12-Loaded PLGA Nanospheres
			Double Solvent Emulsion-Evaporation Method: The Basics
			Double Solvent Emulsion-Evaporation Method of Encapsulating rIL-12 with Homogenization
			Double Solvent Emulsion-Evaporation Method with Ultrasonication
		In Vitro IL-12 Release Characterization: Elution Study
			Characterizing Nanosphere Protein Release Profile via an In Vitro Elution Study
			Elution Profiles: Homogenization and Ultrasonication Methods
		Conclusions and Future Perspectives
		References
	14: Discovery of Cell-Surface Vimentin (CSV) as a Sarcoma Target and Development of CSV-Targeted IL12 Immune Therapy
		Introduction
		Identify Protein Mislocalization for Discovering Novel Tumor-Specific Targets
		CSV May Serve as a Unique and Mislocalized Cell Surface Target for OS Therapy
		CSV-Targeted Linear Peptide Discovery
		CSV-Targeted IL12 Immune Therapy for Treating Residual OS and Inhibiting Metastasis
		References
Part IV: Survivorship and Late Effects
	15: Anthracycline-Induced Cardiotoxicity: Causes, Mechanisms, and Prevention
		Mechanism of Antitumor Action
		Cardiotoxicity
		Monitoring Cardiotoxicity and Heart Function
		Mechanisms of Anthracycline-Induced Cardiotoxicity
		Prevention of Doxorubicin-Induced Cardiotoxicity
		Summary
		References
	16: Exercise and Physical Activity in Patients with Osteosarcoma and Survivors
		Introduction
		Exercise and Physical Activity in Patients Undergoing Cancer Treatment
			Feasibility
			Benefits
		Exercise and Physical Activity in Survivors
			Feasibility
			Benefits
		Summary
		References
Index