Sarcoma: A Practical Guide to Multidisciplinary Management

Preface
About the Editor
Contents
1: Centre-Based Care for Bone and Soft Tissue Sarcoma
	1.1	 Introduction
	1.2	 The Rationale for Multidisciplinary Sarcoma Care
	1.3	 Diagnosis
	1.4	 Treatment of Bone Cancers
	1.5	 Treatment of Soft Tissue Sarcoma
	1.6	 Management of Metastatic Sarcoma
	1.7	 Multidisciplinary Sarcoma Team and Clinic at St. Vincent’s Hospital Melbourne and Peter MacCallum Cancer Centre
		1.7.1	 Sarcoma Clinic
		1.7.2	 Multidisciplinary Meeting
		1.7.3	 Clinical Trials
	1.8	 Impact of Delayed Referral on Patient Outcomes
	1.9	 Recommendation
	1.10	 Conclusion
	References
2: The Epidemiology and Pathogenesis of Sarcoma
	2.1	 Epidemiology of Sarcomas
	2.2	 Pathogenesis of Sarcomas
		2.2.1	 Understanding the Origin of Sarcomas
	2.3	 Genetic Predisposition Syndromes
		2.3.1	 Li-Fraumeni Syndrome
		2.3.2	 Retinoblastoma
		2.3.3	 Neurofibromatosis
		2.3.4	 Other Sarcoma-Associated Genetic Syndromes
	2.4	 Molecular Alterations in Sarcoma
		2.4.1	 Sarcomas with Simple Karyotypes
		2.4.2	 Sarcomas with Complex Karyotypes
	2.5	 Infectious Risk Factors
	2.6	 Immunological Risk Factors
	2.7	 Environmental Risk Factors
		2.7.1	 Radiation Exposure
		2.7.2	 Chemical Exposure
		2.7.3	 Trauma Exposure
	References
3: Anatomic Imaging of Bone and Soft Tissue Sarcoma
	3.1	 Plain Radiography
	3.2	 Ultrasound
	3.3	 Computed Tomography
	3.4	 Magnetic Resonance Imaging
	3.5	 Image Fusion
	3.6	 The Role of Pre-biopsy Imaging
	3.7	 Image-Guided Biopsy: Technique
		3.7.1	 Approach: Broad Principles
	3.8	 Bone Biopsy
	3.9	 Soft Tissue Biopsy
	3.10	 Increasing Role of Interventional Radiology
	3.11	 Artificial Intelligence
	References
4: Nuclear Medicine and Molecular Imaging Techniques
	4.1	 Bone Scans
	4.2	 Metabolic Imaging
		4.2.1	 Thallium-201 Scintigraphy
		4.2.2	 Tc-99m Pentavalent Dimercaptosuccinic Acid (DMSA(V))
		4.2.3	 18FDG PET/CT
			4.2.3.1	 Initial Diagnosis
			4.2.3.2	 Staging and Restaging
			4.2.3.3	 Response to Treatment/Prognosis
	4.3	 Conclusion
	References
5: Biopsy
	5.1	 Background
	5.2	 Who Should Have a Biopsy?
	5.3	 Where Should the Biopsy Be Undertaken?
	5.4	 What Investigations Should Be Undertaken Before Biopsy?
	5.5	 Who Should Perform the Biopsy?
	5.6	 Placement of the Biopsy Entry Site (Figs. 5.4, 5.5, and 5.6)
	5.7	 Biopsy Technique
		5.7.1	 Open Biopsy
		5.7.2	 Percutaneous Biopsy
		5.7.3	 What Tests Should Be Ordered on the Biopsy Material?
		5.7.4	 How Should the Results of the Biopsy Be Interpreted?
	References
6: Bone Tumour Pathology
	6.1	 Introduction
	6.2	 Epidemiology
	6.3	 Classification
	6.4	 Grading and Staging
	6.5	 Diagnostic Approach
	6.6	 Osteogenic Tumours
		6.6.1	 Benign Osteogenic Lesions
		6.6.2	 Osteosarcoma
			6.6.2.1	 Central (Intramedullary) Osteosarcoma
			6.6.2.2	 Surface Osteosarcoma
	6.7	 Chondrogenic Tumours
		6.7.1	 Benign Cartilaginous Tumours
		6.7.2	 Malignant Cartilaginous Tumours
	6.8	 Fibrogenic Tumours
	6.9	 Giant Cell Tumour of the Bone
	6.10	 Ewing Sarcoma
	6.11	 Tumours of Haematopoietic Origin
		6.11.1	 Plasma Cell Myeloma (Multiple Myeloma)
		6.11.2	 Solitary Plasmacytoma of the Bone
		6.11.3	 Primary Non-Hodgkin Lymphoma of the Bone
	6.12	 Langerhans Cell Histiocytosis
	References
7: Soft Tissue Tumour Pathology
	7.1	 General Approach to Soft Tissue Tumours
	7.2	 Handling Biopsy Specimens
	7.3	 Classification of Soft Tissue Tumours
	7.4	 Immunohistochemistry (IHC)
		7.4.1	 Epithelial Markers
		7.4.2	 Myogenic Markers
		7.4.3	 Endothelial (Vascular) Markers
		7.4.4	 Neural Crest/Melanoma Markers
		7.4.5	 Other Useful Markers
	7.5	 Grading Sarcoma
	7.6	 Problems and Limitations of Grading
	7.7	 Sarcoma Staging
	7.8	 Diagnostic Approach to Soft Tissue Tumours with Overlap Patterns
	7.9	 Spindle Cell Pattern
	7.10	 Epithelioid Mesenchymal Tumours
	7.11	 Round Cell Mesenchymal Tumours
	7.12	 Myxoid Tumours
	7.13	 Adipocytic Tumours
	7.14	 Undifferentiated Tumours
	References
8: Immunohistochemistry in Bone and Soft Tissue Tumours
	8.1	 Introduction
	8.2	 History of IHC: “Putting Tail Lights on Antibodies”
	8.3	 Procedure, Technical Considerations and Possible Limitations
		8.3.1	 Preparing the Tissue Sample
		8.3.2	 Selecting Useful Antibodies
		8.3.3	 Detecting and Analysing the Reaction
	8.4	 Immunohistochemical Markers
		8.4.1	 Broad-Spectrum Markers
			8.4.1.1	 Cytokeratins
			8.4.1.2	 Epithelial Membrane Antigen
			8.4.1.3	 S100 Protein
			8.4.1.4	 Desmin
			8.4.1.5	 Smooth Muscle Actin
			8.4.1.6	 CD34
			8.4.1.7	 CD99
		8.4.2	 Novel Markers
			8.4.2.1	 FLI-1
			8.4.2.2	 MDM2 and CDK4
	8.5	 Application and Interpretation of IHC
		8.5.1	 Identification of Benign Tumours
			8.5.1.1	 Solitary Fibrous Tumour
			8.5.1.2	 Nodular Fasciitis
		8.5.2	 Exclusion of Non-mesenchymal/Non-sarcomatous Tumours
			8.5.2.1	 Sarcomatoid Carcinoma
			8.5.2.2	 Malignant Melanoma
		8.5.3	 For Diagnosis of Mesenchymal Tumours
			8.5.3.1	 Rhabdomyosarcomas
			8.5.3.2	 Gastrointestinal Stromal Tumours
			8.5.3.3	 Malignant Vascular Tumours
	References
9: Molecular Genetics in the Multidisciplinary Management of Sarcoma
	9.1	 Introduction
	9.2	 Molecular Aberrations in Sarcoma
		9.2.1	 Chromosomal Translocations
		9.2.2	 Gene Amplifications
		9.2.3	 Activating Mutations of Proto-oncogenes
		9.2.4	 Germline Mutations
	9.3	 Molecular Techniques
		9.3.1	 Conventional Karyotyping
		9.3.2	 Fluorescence In Situ Hybridisation
		9.3.3	 Reverse Transcription-Polymerase Chain Reaction
		9.3.4	 Immunohistochemistry
	9.4	 Diagnosis
		9.4.1	 Liposarcoma
		9.4.2	 Synovial Sarcoma
		9.4.3	 Small Round Cell Tumours
		9.4.4	 Nodular Fasciitis
	9.5	 Prognosis
	9.6	 Treatment
		9.6.1	 Imatinib in GIST
		9.6.2	 Imatinib in the Treatment of Other Soft Tissue Tumours
		9.6.3	 The Future of Other Targeted Therapies in Sarcoma
	9.7	 Conclusion
	References
10: The Role of Radiotherapy for Sarcoma
	10.1	 Introduction
	10.2	 The Role of External Beam Radiotherapy in Soft Tissue Sarcoma of Extremity
	10.3	 Tumour Grade and Radiotherapy
	10.4	 The Timing of External Beam Radiotherapy
	10.5	 Target Delineation and Definition of Margins
	10.6	 Chemoradiotherapy
	10.7	 Brachytherapy
	10.8	 The Role of Radiotherapy in Primary Bone Sarcoma
	10.9	 Osteosarcoma
	10.10	 Ewing Sarcoma
	10.11	 Chondrosarcoma
	10.12	 Whole-Lung Irradiation
	10.13	 Chordoma
	10.14	 Retroperitoneal Sarcoma
	References
11: The Role of Systemic Therapies in the Management of Soft Tissue Sarcoma
	11.1	 Introduction
	11.2	 Systemic Therapy in Localized STS
	11.3	 Systemic Therapy in Advanced/Metastatic STS
	11.4	 Traditional Cytotoxic Agents
		11.4.1	 Doxorubicin and/or Ifosfamide
		11.4.2	 Other Traditional Cytotoxic Agents
		11.4.3	 Histotype-Specific Cytotoxic Agents
			11.4.3.1	 Trabectedin
			11.4.3.2	 Eribulin
		11.4.4	 Molecularly Targeted Agents
		11.4.5	 Tyrosine Kinase Inhibitors (TKIs) or Multi-targeted Kinase Inhibitors
			11.4.5.1	 Pazopanib
	11.5	 Treatment Considerations for Certain STS Histology Subtypes
		11.5.1	 Angiosarcoma
		11.5.2	 Solitary Fibrous Tumour (SFT)
		11.5.3	 Perivascular Epithelioid Cell tumour (PEComa)
		11.5.4	 Alveolar Soft Part Sarcoma (ASPS)
	11.6	 Treatment Considerations for Certain Benign/Intermediate-Grade Soft Tissue Tumours
		11.6.1	 Dermatofibrosarcoma Protuberans (DFSP)
		11.6.2	 Pigmented Villonodular Synovitis (PVNS)
		11.6.3	 Desmoid-Type Fibromatosis
	11.7	 Gynaecological Sarcomas
		11.7.1	 Uterine Sarcoma
		11.7.2	 Uterine Undifferentiated Pleomorphic Sarcoma (UUPS)
		11.7.3	 Uterine Leiomyosarcoma (ULMS)
		11.7.4	 Endometrial Stromal Sarcoma (ESS)
		11.7.5	 Ovarian Sarcoma
	References
12: The Role of Systemic Therapies in the Management of Bone Sarcoma
	12.1	 Introduction
	12.2	 Special Considerations
		12.2.1	 Genetic
		12.2.2	 Adolescent and Young Adults
		12.2.3	 Fertility Preservation
		12.2.4	 Disease and Late Effects Surveillance
	12.3	 Osteosarcoma
		12.3.1	 Metastatic Disease
		12.3.2	 Post-Treatment Surveillance
		12.3.3	 Recurrent and Relapsed Disease
	12.4	 Ewing Sarcoma Family of Tumours
		12.4.1	 Metastatic Disease
		12.4.2	 Post-Treatment Surveillance
		12.4.3	 Recurrent and Relapsed Disease
		12.4.4	 Special Considerations
			12.4.4.1	 Local Therapy
	12.5	 Giant Cell Tumour of Bone
		12.5.1	 Unresectable or Metastatic Disease
		12.5.2	 Post-Treatment Surveillance
	12.6	 Chondrosarcoma
		12.6.1	 Metastatic Disease
		12.6.2	 Surveillance
		12.6.3	 Special Consideration
			12.6.3.1	 Novel Therapies
	12.7	 Chordoma
		12.7.1	 Surveillance
		12.7.2	 Relapsed and Recurrent Disease
	References
13: The Importance of Margins in Sarcoma Surgery
	13.1	 Introduction
	13.2	 Special Considerations
		13.2.1	 Response to Neoadjuvant Treatment
		13.2.2	 Tumour Grade
		13.2.3	 Unplanned Excision
		13.2.4	 Histotype and Depth
	13.3	 MSTS Classification of Surgical Margins
		13.3.1	 Intralesional Margin
		13.3.2	 Marginal Margin
		13.3.3	 Wide Margin
		13.3.4	 Radical Margin
		13.3.5	 Adequacy of Surgical Margins
		13.3.6	 Amputation
	References
14: Surgical Management of Lower Limb Sarcomas
	14.1	 Anatomical Considerations
		14.1.1	 Soft Tissue Sarcomas
			14.1.1.1	 Buttock Tumours (Fig. 14.1)
			14.1.1.2	 Quadriceps Tumours (Fig. 14.2)
			14.1.1.3	 Adductor Compartment Tumour
			14.1.1.4	 Hamstring Compartment
			14.1.1.5	 Popliteal Tumours
			14.1.1.6	 Calf Tumours
			14.1.1.7	 Anterior Lower Leg Tumours
			14.1.1.8	 Foot Tumours
		14.1.2	 Bone Sarcomas
			14.1.2.1	 Proximal Femoral Tumours
			14.1.2.2	 Distal Femoral Tumours
			14.1.2.3	 Proximal Tibial Tumours
			14.1.2.4	 Distal Tibial Sarcomas
		14.1.3	 Investigations
			14.1.3.1	 Plain Radiographs
			14.1.3.2	 Anatomic Imaging
			14.1.3.3	 Functional Imaging
			14.1.3.4	 Systemic Imaging
		14.1.4	 Biopsy
		14.1.5	 Preoperative Preparation
		14.1.6	 Operative Preparation
			14.1.6.1	 Anaesthetic
			14.1.6.2	 Antibiotics
			14.1.6.3	 Urinary Catheter
		14.1.7	 Positioning for Soft Tissue Sarcoma Resection
			14.1.7.1	 Buttock Tumours
		14.1.8	 Positioning for Bone Sarcoma Resection
			14.1.8.1	 Proximal and Total Femoral Tumours
			14.1.8.2	 Knee Tumours
			14.1.8.3	 Foot Tumours
	14.2	 Surgical Technique
		14.2.1	 Key Points for Resection of Soft Tissue Sarcomas
		14.2.2	 Key Points for Resection of Bone Sarcomas
			14.2.2.1	 Proximal Femoral Resection
			14.2.2.2	 Distal Femoral Resection
			14.2.2.3	 Total Femoral Resection (Fig. 14.8)
			14.2.2.4	 Proximal Tibial Resection
			14.2.2.5	 Distal Tibial Resection
			14.2.2.6	 Amputation
	References
15: Surgical Management of Upper Limb Sarcomas
	15.1	 Introduction
	15.2	 Soft Tissue Sarcomas
		15.2.1	 Anatomic Considerations
		15.2.2	 Shoulder Girdle Tumours
		15.2.3	 Upper Arm Tumours
		15.2.4	 Forearm Tumours (Fig. 15.3)
		15.2.5	 Wrist and Hand Tumours
	15.3	 Bone Sarcomas
		15.3.1	 Anatomic Considerations
	15.4	 Preoperative Staging
	15.5	 Anatomic Imaging
	15.6	 Functional Imaging
	15.7	 Biopsy
	15.8	 Systemic Imaging
	15.9	 Surgery
		15.9.1	 Soft Tissue Sarcomas
		15.9.2	 Bone Sarcomas
		15.9.3	 Humerus (Fig. 15.4)
		15.9.4	 Elbow
		15.9.5	 Forearm
		15.9.6	 Amputation
	References
16: Surgical Management of Pelvic Sarcomas
	16.1	 Introduction
	16.2	 Bone Tumours
		16.2.1	 Soft Tissue Tumours
		16.2.2	 Presenting Symptoms and Signs
		16.2.3	 Investigations
			16.2.3.1	 Plain Radiography
			16.2.3.2	 Computed Tomography
			16.2.3.3	 Magnetic Resonance Imaging
			16.2.3.4	 Functional Imaging
			16.2.3.5	 Angiography
			16.2.3.6	 Ureterogram/Cystogram
		16.2.4	 Biopsy
	16.3	 Preoperative Preparation
		16.3.1	 Positioning
		16.3.2	 Surgical Considerations
			16.3.2.1	 Type I Tumours
			16.3.2.2	 Type II Tumours
			16.3.2.3	 Type III Tumours
			16.3.2.4	 Type IV Tumours
				Margins
				Amputation
	References
17: Surgical Management of Chest Wall Sarcomas
	17.1	 Historical Note
	17.2	 Primary Chest Wall Malignancies
	17.3	 Clinical Presentation
		17.3.1	 Diagnosis
		17.3.2	 Treatment
		17.3.3	 Preoperative Evaluation
	17.4	 Principles of Surgery
		17.4.1	 Resection
		17.4.2	 Reconstruction
		17.4.3	 Choice of Material
		17.4.4	 Tips/Tricks
	17.5	 Future Directions
	17.6	 Summary
	References
18: Surgical Management of Pulmonary Metastases from Sarcoma
	18.1	 Introduction
	18.2	 The Oligometastatic Disease Concept
	18.3	 Assessment for Surgery
	18.4	 Surgical Oncology Principles
	18.5	 Conduct of Surgery
		18.5.1	 Access
		18.5.2	 Wedge Metastasectomy
		18.5.3	 Anatomic Sublobar Resections
		18.5.4	 Bronchoplastic Resections
	18.6	 Complications of Surgery
	References
19: Management of Retroperitoneal Sarcomas
	19.1	 Epidemiology and Staging
	19.2	 Histologic Subtypes
		19.2.1	 Liposarcomas
		19.2.2	 Leiomyosarcomas
		19.2.3	 Other Histologies
	19.3	 Patient Presentation
	19.4	 Diagnostic Pathway
		19.4.1	 Imaging
		19.4.2	 Core Needle Biopsy
		19.4.3	 The Transatlantic Retroperitoneal Sarcoma Working Group
	19.5	 Management
		19.5.1	 Multidisciplinary Team
		19.5.2	 When Is a Retroperitoneal Sarcoma Deemed Unresectable?
	19.6	 Preoperative Assessment
	19.7	 The Surgical Strategy
	19.8	 Prognosis
		19.8.1	 Neoadjuvant and Adjuvant Therapies
			19.8.1.1	 Radiotherapy
			19.8.1.2	 Chemotherapy
		19.8.2	 Follow-Up
	19.9	 Management of Recurrent Disease
	19.10	 Management of Metastatic Disease
	References
20: Soft Tissue Reconstructions After Sarcoma Resection
	20.1	 Challenges of Sarcoma Reconstruction
	20.2	 Goals and Principles of Reconstruction
	20.3	 Wound Assessment and Flap Selection
	20.4	 Regional Reconstruction: Lower Limb
		20.4.1	 Upper Limb
	20.5	 Common Flaps
	20.6	 Propeller Flap or Regional Fasciocutaneous Perforator Flaps
		20.6.1	 Application in Sarcoma Reconstruction
		20.6.2	 Latissimus Dorsi Flap
			20.6.2.1	 History
		20.6.3	 Application in Sarcoma Reconstruction
			20.6.3.1	 Free Flap
			20.6.3.2	 Local Flap
			20.6.3.3	 Functional Reconstruction
		20.6.4	 Gracilis Flap
			20.6.4.1	 History
			20.6.4.2	 Application in Sarcoma Reconstruction
		20.6.5	 Parascapular/Scapular Flaps
			20.6.5.1	 History
			20.6.5.2	 Application in Sarcoma Reconstruction
			20.6.5.3	 Local Flap
			20.6.5.4	 Free Flap
		20.6.6	 Anterolateral Thigh Flap
			20.6.6.1	 History
			20.6.6.2	 Application in Sarcoma Reconstruction
			20.6.6.3	 Free Flap
			20.6.6.4	 Pedicle Flap
	References
21: Management of Metastatic Sarcoma
	21.1	 Radiotherapy
		21.1.1	 Treatment of Oligometastasis
		21.1.2	 Stereotactic Body Radiotherapy
	21.2	 Surgery
	21.3	 Chemotherapy
	References