Radiation Therapy for Sarcomas and Skin Cancers: A Practical Guide on Treatment Techniques

Contents
1: Extremity Soft Tissue Sarcoma
	1.1	 Introduction
	1.2	 Staging System
	1.3	 Treatment Strategies to Be Discussed in this Chapter
	1.4	 Management Principles
		1.4.1	 Workup
		1.4.2	 Staging
		1.4.3	 Treatment Planning
		1.4.4	 Integration of Primary Surgery with Multimodality Treatment
		1.4.5	 Areas of Controversy
	1.5	 Radiation Therapy Techniques
		1.5.1	 Technical Considerations
			1.5.1.1	 CT Simulation
			1.5.1.2	 Target Definitions
			1.5.1.3	 Radiation Planning
		1.5.2	 Preoperative External Beam Radiation Therapy
			1.5.2.1	 Hypofractionation
		1.5.3	 Postoperative External Beam Radiation Therapy
		1.5.4	 Brachytherapy
		1.5.5	 Intraoperative Radiation Therapy (IORT)
	1.6	 Chemotherapy
		1.6.1	 Overview
		1.6.2	 Combinations of Radiation Therapy and Chemotherapy
		1.6.3	 Role of Biologic Therapy in Combination with Radiation Therapy
	1.7	 Sequelae of Treatment and Dose Constraints
		1.7.1	 Follow-Up/Surveillance
	References
2: Retroperitoneal Sarcoma
	2.1	 Introduction to Retroperitoneal Sarcoma
	2.2	 Historical Outcomes
	2.3	 Management Principles
	2.4	 Surgery
	2.5	 Radiotherapy
		2.5.1	 Intraoperative Radiotherapy and Postoperative Brachytherapy
	2.6	 Systemic Therapy
	2.7	 Radiotherapy Techniques and Planning
	2.8	 CT Simulation
	2.9	 Target Volumes
	2.10	 Prescription Dose
	2.11	 Boosts to High-Risk Margin and GTV
	2.12	 Target Coverage
	2.13	 Radiation Technique
		2.13.1	 Image-Guided Radiation Therapy (IGRT)
	2.14	 Organs at Risk and Radiation Tolerance Doses
		2.14.1	 DVH (Dose Volume Histogram) Considerations
	2.15	 Current Trials
		2.15.1	 STRASS EORTC 62092-22092 (ClinicalTrials.gov NCT01344018), Ref [54]
		2.15.2	 Phase I/Phase II Trial of Preoperative IG-IMPT or IMRT with Simultaneous Integrated Boost (SIB) for Retroperitoneal Sarcomas (ClinicalTrials.gov NCT01659203), Ref [64]
		2.15.3	 NRG-DT001 (ClinicalTrials.gov NCT03217266), Ref [50]
	2.16	 Future Directions
	2.17	 Treatment Algorithm
	2.18	 Summary
	References
3: Gynecologic Sarcomas
	3.1	 Introduction
		3.1.1	 Epidemiology and Risk Factors
		3.1.2	 Histopathology of Gynecologic Sarcomas
		3.1.3	 General Management Strategy
		3.1.4	 Current Staging for Gynecologic Sarcomas
		3.1.5	 Prognosis by Tumor Stage
	3.2	 Management Principles
		3.2.1	 Presentation, Diagnosis, and Staging Workup
		3.2.2	 Uterine Sarcoma
		3.2.3	 Cervical Sarcoma
		3.2.4	 Vaginal/Vulvar Sarcoma
		3.2.5	 Ovarian Sarcoma
		3.2.6	 Management of Gynecologic Sarcomas
		3.2.7	 Uterine Sarcoma
		3.2.8	 Cervical Sarcoma
		3.2.9	 Vaginal/Vulvar Sarcoma
		3.2.10	 Ovarian Sarcoma
		3.2.11	 Recurrent Disease/Palliation
	3.3	 Radiation Therapy Techniques and Planning
		3.3.1	 Uterine and Cervical Sarcoma
			3.3.1.1	 Adjuvant Radiotherapy
			3.3.1.2	 Simulation
			3.3.1.3	 Volume Delineation
			3.3.1.4	 Treatment Planning Considerations
			3.3.1.5	 Definitive Radiotherapy/Chemoradiotherapy
			3.3.1.6	 Simulation
			3.3.1.7	 Volume Delineation
			3.3.1.8	 Treatment Planning Considerations
		3.3.2	 Vulvar/Vaginal Sarcoma
			3.3.2.1	 Adjuvant Radiotherapy
			3.3.2.2	 Simulation
			3.3.2.3	 Volume Delineation
			3.3.2.4	 Treatment Planning Considerations
			3.3.2.5	 Definitive Radiotherapy/Chemoradiotherapy
		3.3.3	 Ovarian Sarcoma
			3.3.3.1	 Radiation-Related Toxicities and Radiotherapy Dose Constraints for Organ at Risk Volumes
		3.3.4	 Recurrent and Metastatic Disease
			3.3.4.1	 Interstitial Brachytherapy
			3.3.4.2	 Stereotactic Body Radiotherapy
			3.3.4.3	 Palliative Radiotherapy Treatments
			3.3.4.4	 Physics and Quality Assurance Considerations
			3.3.4.5	 Treatment Algorithm
	3.4	 Summary
	References
4: Radiation Therapy for Oligometastatic Sarcomas
	4.1	 Systemic Therapy for Oligometastatic Sarcoma
		4.1.1	 Standard Chemotherapy
		4.1.2	 Targeted Therapies and Emerging Systemic Treatments
	4.2	 Metastasectomy of Sarcoma Oligometastases
	4.3	 Stereotactic Body Radiation Therapy (SBRT) of Oligometastases
	4.4	 SBRT Technique
		4.4.1	 Spine SBRT
			4.4.1.1	 Image Guidance
			4.4.1.2	 Treatment Delivery
			4.4.1.3	 Imaging and Planning
			4.4.1.4	 Target Volumes
			4.4.1.5	 Patient Selection
			4.4.1.6	 Treatment Dose
		4.4.2	 Lung SBRT
			4.4.2.1	 Simulation
			4.4.2.2	 Motion Management
			4.4.2.3	 Image Guidance
			4.4.2.4	 Target Volumes
			4.4.2.5	 Dose
	4.5	 Concluding Remarks
	References
5: Radiotherapy for Pediatric Sarcomas
	5.1	 Introduction
	5.2	 Management Principles
		5.2.1	 Workup for Pediatric Sarcomas
		5.2.2	 Staging for Pediatric Sarcomas
		5.2.3	 Treatment Algorithm for Pediatric Bone and Soft Tissue Sarcoma
			5.2.3.1	 Ewing Sarcoma
			5.2.3.2	 Rhabdomyosarcoma
			5.2.3.3	 Non-RMS Soft Tissue Sarcoma
			5.2.3.4	 Osteosarcoma
		5.2.4	 Radiation Therapy Techniques and Planning
			5.2.4.1	 Preparing to Treat the Patient
			5.2.4.2	 Simulation
			5.2.4.3	 Target Definitions
		5.2.5	 Curative Dose Recommendations
			5.2.5.1	 Ewing Sarcoma
			5.2.5.2	 RMS
			5.2.5.3	 Non-RMS Soft Tissue Sarcoma
			5.2.5.4	 Osteosarcoma
		5.2.6	 Treatment Planning Considerations
		5.2.7	 Modalities of Radiation
			5.2.7.1	 Physics/Quality Assurance
	5.3	 Summary
	References
6: Concurrent Chemoradiation Therapy for Soft Tissue Sarcoma
	6.1	 Introduction
	6.2	 Concurrent Radiotherapy with Anthracycline-Based Chemotherapy
	6.3	 Improvements in Concurrent CRT
	6.4	 Concurrent Radiotherapy and Immunotherapy
	6.5	 Concurrent Radiotherapy and MDM2 Inhibitor, AMG-232
	6.6	 Concurrent Radiotherapy and Taxanes for Angiosarcoma
	6.7	 Adjuvant Chemotherapy for Resectable Soft Tissue Sarcomas (STS)
	6.8	 Systemic Therapy in Advanced/Metastatic STS
	6.9	 Progression After First-Line Chemotherapy for Metastatic Disease
	6.10	 Summary
	References
7: Particle Therapy for Head and Neck Sarcomas
	7.1	 Introduction
	7.2	 Essentials of Particle Beam Radiotherapy
		7.2.1	 Characteristics of Charged Particle Beams
		7.2.2	 Delivery Technologies of PBRT
	7.3	 Registration and Planning
		7.3.1	 Patient Registration and Immobilization
		7.3.2	 Definition and Delineation of Target Volumes
			7.3.2.1	 Beam Directions
		7.3.3	 Dose and Fractionation of PBRT
			7.3.3.1	 Soft Tissue Sarcoma and Osteosarcoma
			7.3.3.2	 Rhabdomyosarcoma
			7.3.3.3	 Chordoma and Chondrosarcoma
		7.3.4	 Dose Constrains for Organs at Risk (OARs)
		7.3.5	 Reirradiation
		7.3.6	 Setup Verification
	7.4	 The Use of Chemotherapy with PBRT
	7.5	 Clinical Outcomes
		7.5.1	 Soft Tissue Sarcomas and Osteosarcoma
		7.5.2	 Rhabdomyosarcoma
		7.5.3	 Chordoma and Chondrosarcoma
	7.6	 Future Direction
	References
8: Desmoid Tumors
	8.1	 Introduction
	8.2	 Management Principles
		8.2.1	 Workup
		8.2.2	 Observation
		8.2.3	 Surgery
		8.2.4	 Radiation Therapy
		8.2.5	 Systemic Therapy
		8.2.6	 Follow-Up Guidelines Based on Recurrence Patterns and Prognosis
		8.2.7	 Management of Recurrent Disease
	8.3	 Radiation Therapy Techniques and Planning
		8.3.1	 Simulation
		8.3.2	 Treatment Volumes
		8.3.3	 Treatment Techniques
		8.3.4	 Dose
		8.3.5	 Dose Constraints
	8.4	 Treatment Algorithm
	References
9: Solitary Fibrous Tumors/Hemangiopericytoma
	9.1	 Introduction
		9.1.1	 Nomenclature and Historical Perspective
		9.1.2	 Epidemiology and Clinical Manifestations
			9.1.2.1	 Pleural/Intrathoracic SFTs
			9.1.2.2	 Hemangiopericytoma
			9.1.2.3	 Extrathoracic/Soft Tissue SFTs
	9.2	 Diagnosis
		9.2.1	 Initial Evaluation
		9.2.2	 Imaging
		9.2.3	 Pathology
		9.2.4	 Risk Stratification and Staging
			9.2.4.1	 Intrathoracic SFTs
			9.2.4.2	 Intracranial SFTs
			9.2.4.3	 Extrathoracic SFTs
	9.3	 Treatment Strategies
		9.3.1	 Surgery
		9.3.2	 Radiotherapy
			9.3.2.1	 Indications for Adjuvant Radiation
			9.3.2.2	 Indications for Definitive Radiation
		9.3.3	 Systemic Therapy
	9.4	 Posttreatment and Future Direction
		9.4.1	 Surveillance
		9.4.2	 Management of Recurrence
		9.4.3	 Future Directions
	9.5	 Clinical Treatment Planning Considerations
		9.5.1	 Patient Setup and Immobilization
		9.5.2	 Simulation
		9.5.3	 Image Guidance and Motion Management for Optimized Treatment Delivery
		9.5.4	 Radiation Modalities/Plan Optimization
			9.5.4.1	 Intrathoracic SFTs
			9.5.4.2	 Intracranial HPCs
			9.5.4.3	 Extrathoracic SFTs
		9.5.5	 Dosimetric Treatment Planning Considerations
			9.5.5.1	 Target Volumes
				Intrathoracic SFTs
					Gross Tumor Volume (GTV)
					Clinical Target Volume (CTV)
					Internal Target Volume (ITV)
					Planning Target Volume (PTV)
				Intracranial HPCs
					Gross Tumor Volume (GTV)
					Clinical Target Volume (CTV)
					Planning Target Volume (PTV)
				Extrathoracic SFTs
					Gross Tumor Volume (GTV)
					Clinical Target Volume (CTV)
					Planning Target Volume (PTV)
			9.5.5.2	 Dose Prescription
				General Dose Guidelines
			9.5.5.3	 Organs-at-Risk (OAR) Tolerances
		9.5.6	 Physics and Quality Assurance
			9.5.6.1	 Equipment-Specific QA
			9.5.6.2	 Patient-Specific QA
			9.5.6.3	 Procedure-Specific QA
	9.6	 Summary of Radiotherapy Treatment Algorithm
	9.7	 Conclusion
	References
10: Radiation Therapy for Angiosarcomas
	10.1	 Introduction
	10.2	 Epidemiology
	10.3	 Etiology
	10.4	 Imaging
	10.5	 Pathology
	10.6	 Clinical Subtypes
		10.6.1	 Primary Cutaneous Angiosarcoma
			10.6.1.1	 Diagnosis
			10.6.1.2	 Management
				Surgery
				Radiation Therapy
					Simulation
					Target Delineation Including Organs at Risk (OAR)
					Treatment Planning
					Treatment Delivery
					Safety/Quality Assurance (QA)
				Systemic Therapy
		10.6.2	 Angiosarcoma Associated with Lymphedema
			10.6.2.1	 Diagnosis
			10.6.2.2	 Management
		10.6.3	 Breast Angiosarcoma
			10.6.3.1	 Diagnosis
			10.6.3.2	 Management
		10.6.4	 Soft Tissue Angiosarcoma
		10.6.5	 Radiation-Induced Angiosarcoma
			10.6.5.1	 Diagnosis
			10.6.5.2	 Management
	10.7	 Summary
	References
11: Radiation for Dermatofibrosarcoma Protuberans
	11.1	 Introduction
		11.1.1	 Staging
	11.2	 Management Principles
		11.2.1	 Workup
		11.2.2	 Treatment Options
			11.2.2.1	 Surgery
			11.2.2.2	 Radiotherapy
			11.2.2.3	 Systemic Therapy
			11.2.2.4	 Follow-Up
	11.3	 Radiation Therapy Techniques and Planning
		11.3.1	 Choice of Modality
		11.3.2	 Simulation
		11.3.3	 Target Definition
		11.3.4	 Dose
	11.4	 Physics/QA
	11.5	 Treatment Algorithm
	11.6	 Summary
	References
12: Radiation Therapy in the Management of Cutaneous Squamous Cell Carcinomas
	12.1	 Early Stage Disease
		12.1.1	 Surgical Management of Early Stage cSCCs
		12.1.2	 Indications for Adjuvant Radiation After Surgery for Early Stage cSCCs
		12.1.3	 Radiation as Primary Management of Early Stage cSCCs
		12.1.4	 Radiation Dose and Fractionation Schemes for the Management of Early Stage cSCCs
		12.1.5	 Radiation Techniques for the Management of Early Stage cSCCs
	12.2	 Advanced Disease
		12.2.1	 Surgical Management of Advanced Stage cSCCs
		12.2.2	 Indications for Adjuvant Radiation After Surgery for Advanced Stage cSCCs
		12.2.3	 Radiation as the Primary Management of Advanced Stage cSCCs
		12.2.4	 Radiation Dose and Fractionation Schemes for the Management of Advanced Stage cSCCs
		12.2.5	 Radiation Techniques for the Management of Advanced Stage cSCCs
	12.3	 Conclusion
	References
13: Basal Cell Carcinoma
	13.1	 Epidemiology
	13.2	 Natural History
	13.3	 Subtypes
		13.3.1	 Risk Stratification
		13.3.2	 Management Options
			13.3.2.1	 Excision
			13.3.2.2	 MOHS Micrographic Surgery (MMS)
			13.3.2.3	 Curettage and Electrodesiccation (C&E)
			13.3.2.4	 Superficial Therapies
		13.3.3	 Radiation Therapy
			13.3.3.1	 Patient Selection
			13.3.3.2	 Modality Comparison
			13.3.3.3	 Treatment Recommendations
		13.3.4	 Radiation Techniques
		13.3.5	 External Beam Radiation
			13.3.5.1	 Orthovoltage/Supervoltage
			13.3.5.2	 Electron Beam
			13.3.5.3	 Patient Setup
			13.3.5.4	 Prescription
			13.3.5.5	 Electron Arc Therapy
			13.3.5.6	 Photon Beam Therapy
			13.3.5.7	 Brachytherapy
		13.3.6	 Applicators
			13.3.6.1	 Contact BT
			13.3.6.2	 Surface Flaps
			13.3.6.3	 Custom Applicators
			13.3.6.4	 Treatment Planning and Prescription
			13.3.6.5	 Treatment Toxicity and Patient Management
			13.3.6.6	 Palliation
	13.4	 Systemic Therapy
		13.4.1	 Targeted Therapy: Hedgehog Pathway
		13.4.2	 Non-Targeted Agents
	References
14: Melanoma
	14.1	 Pathology
		14.1.1	 Epidemiology
		14.1.2 Aetiology
			14.1.2.1	 Environmental
			14.1.2.2	 Genetic
		14.1.3 Radial and Vertical Growth
		14.1.4 Subtypes
			14.1.4.1	 Superficial Spreading Melanoma
			14.1.4.2	 Nodular Melanoma
			14.1.4.3	 Lentigo Maligna Melanoma
			14.1.4.4	 Desmoplastic Melanoma
			14.1.4.5	 Acral Lentiginous Melanoma
	14.2	 Staging
		14.2.1 T Category
		14.2.2 N Category
		14.2.3 M Category
		14.2.4 Clinical and Pathologic Prognostic Stage Groups
	14.3	 Initial Assessment
		14.3.1	 Approach to Pigmented Lesion
			14.3.1.1	 History
			14.3.1.2	 Examination
			14.3.1.3	 Investigations
		14.3.2 Workup of Biopsy-Confirmed Melanoma
			14.3.2.1	 All Patients
			14.3.2.2	 Patients with No Clinical Evidence of Regional Nodal or Distant Metastases
			14.3.2.3	 Patients with Clinical Evidence of Regional Nodal or Distant Metastases
	14.4	 Treatment: Primary Cutaneous Melanoma
		14.4.1	 Invasive Malignant Melanoma
			14.4.1.1	 Wide Local Excision
			14.4.1.2	 Radiation Therapy
			14.4.1.3	 Adjuvant Therapy
		14.4.2 In Situ Melanoma
	14.5	 Treatment: Regional Lymphatics
		14.5.1	 Approach to the Clinically Involved Nodal Basin
			14.5.1.1	 Surgery for Resectable Regional Nodal Metastases
			14.5.1.2	 Adjuvant Therapy Following Regional Lymph Node Dissection
			14.5.1.3	 Neoadjuvant Therapy Prior to Regional Lymph Node Dissection
			14.5.1.4	 Unresectable Regional Nodal Metastases
		14.5.2 Approach to the Clinically Uninvolved Nodal Basin
			14.5.2.1	 Sentinel Lymph Node Biopsy
			14.5.2.2	 Adjuvant Therapy Following Sentinel Lymph Node Biopsy
			14.5.2.3	 Approach to Satellite Lesions or in-Transit Metastases
	14.6	 Treatment: Distant Metastases and Unresectable Regional Nodal Metastases
		14.6.1	 Systemic Therapy
			14.6.1.1	 Cytotoxic Chemotherapy
			14.6.1.2	 Targeted Therapies
			14.6.1.3	 Immunotherapy
		14.6.2 Local Therapy for Extracranial Oligometastases
			14.6.2.1	 Surgical Metastasectomy
			14.6.2.2	 Radiation Therapy
		14.6.3 Approach to Brain Metastases
	14.7	 Head and Neck Mucosal Melanoma
		14.7.1	 Pathology, Epidemiology and Staging
		14.7.2 Treatment
	14.8	 Other Mucosal Melanoma
		14.8.1	 Pathology, Epidemiology and Staging
		14.8.2 Treatment
	14.9	 Ocular Melanoma
		14.9.1	 Pathology, Epidemiology and Staging
		14.9.2 Treatment
	14.10	 Radiation Therapy Techniques
		14.10.1 Considerations in Selecting a Radiation Technique
		14.10.2 Simulation
		14.10.3 Daily Treatment Position and Image Verification
		14.10.4 Treatment Planning, Volume Delineation and Recommended Dose
			14.10.4.1	 Adjuvant Radiation Therapy for High-Risk Nodal Metastases
			14.10.4.2	 Adjuvant Radiation Therapy for High-Risk Primary Cutaneous Melanoma of the Head and Neck
			14.10.4.3	 Definitive Radiation Therapy for Lentigo Maligna
			14.10.4.4	 Definitive Radiation Therapy for Mucosal Melanoma of the Head and Neck
		14.10.5 Dose Specification
			14.10.5.1	 Megavoltage (MV) Energy Photon Treatments (3DCRT, IMRT/VMAT)
			14.10.5.2	 Electron Treatments
			14.10.5.3	 Superficial (Kilovoltage Energy) Photon Treatments
	14.11	 Principles of Stereotactic Ablative Radiation Therapy for Extracranial Oligometastases
		14.11.1 Highly Hypofractionated Treatment to Small Fields with Steep Dose Gradients
		14.11.2 Motion Management
		14.11.3 Image Guidance
		14.11.4 Quality Assurance
	14.12	 Patient-Specific Radiation Quality Assurance for Modern Techniques
	14.13	 Normal Tissue Complications From Radiation Therapy for Melanoma
		14.13.1 Factors Affecting Risk of Normal Tissue Complications
			14.13.1.1	 Patient Factors
			14.13.1.2	 Tumour Factors
			14.13.1.3	 Treatment Factors
		14.13.2 Early Radiation Toxicity Following Radiation Therapy for Melanoma
			14.13.2.1	 Head and Neck
			14.13.2.2	 Axilla
			14.13.2.3	 Groin
		14.13.3 Late Toxicities Following Radiation Therapy for Melanoma
			14.13.3.1	 General
			14.13.3.2	 Head and Neck
			14.13.3.3	 Adjuvant Treatment of Axilla
			14.13.3.4	 Adjuvant Treatment of Groin
		14.13.4 Strategies to Minimize Radiation Toxicity
			14.13.4.1	 Patient Factors
			14.13.4.2	 Treatment Factors
	14.14	 Summary for Role of RT in Melanoma
	References
15: Merkel Cell Carcinoma
	15.1	 Introduction
		15.1.1	 Clinical Presentation
		15.1.2	 Risk Factors and Pathogenesis
		15.1.3	 Staging
	15.2	 Management Principles
		15.2.1	 Initial Diagnosis
		15.2.2	 Treatment
		15.2.3	 Current Role of Adjuvant Therapy in MCC
			15.2.3.1	 Radiation Therapy
			15.2.3.2	 Adjuvant Systemic Therapy
			15.2.3.3	 Metastatic Disease
			15.2.3.4	 Role of Radiation
	15.3	 Radiation Therapy Techniques and Planning
		15.3.1	 Radiation Technical Considerations
		15.3.2	 Target Delineation
		15.3.3	 Dose Treatment Recommendations
	15.4	 Summary
	References
16: Treatment of Cutaneous Lymphomas: Topical, Systemic, and Radiation Therapies
	16.1	 Introduction
	16.2	 Management Approaches
		16.2.1	 Primary Cutaneous B-Cell Lymphomas
			16.2.1.1	 Radiotherapy
			16.2.1.2	 Other Therapies
		16.2.2	 Cutaneous T-Cell Lymphoma (CTCL) Including Primary Cutaneous CD30-Positive Lymphomas (Such as pcALCL and LyP) and Mycosis Fungoides (MF)
			16.2.2.1	 Radiation Therapy (RT)
			16.2.2.2	 Mycosis Fungoides
			16.2.2.3	 Topical Therapies
			16.2.2.4	 Phototherapy
			16.2.2.5	 Systemic Therapies for CTCL
	References