Treatment of Neuroblastoma

Brian H. Kushner,Susan L.Cohn, Katherine K. Matthay, Nai-Kong V. Cheung, Michael P. La Quaglia, Daphne A. Haas-Kogan, Suzanne L.Wolden,Stephan A.Grupp, Irene Y. Cheung, Peter F. Ambros

Contents

11.1 Low-Risk Neuroblastoma 124

11.1.1 Introduction 124

11.1.2 Clinical Presentation 124

11.1.3 Clinical Staging 125

11.1.4 Biologic Prognostic Markers 125

11.1.5 Treatment 125

11.1.5.1 Localized Tumors with No Regional Spread 126

11.1.5.2 Regionally Invasive Unilateral

Localized Tumors 127

11.1.5.3 Stage 4S 128

11.1.6 Future Directions 129

11.1.7 Conclusion 129

References 129

11.2 Intermediate-Risk Neuroblastoma 131

11.2.1 Introduction 131

11.2.2 Clinical Presentation 131

11.2.3 Clinical Staging 133

11.2.4 Biologic Prognostic Markers 133

11.2.5 Treatment 133

11.2.5.1 Treatment for Stage-3 Neuroblastoma ... 134

11.2.5.2 Treatment for Stage-4S Neuroblastoma. . . 134

11.2.5.3 Treatment of Infant Stage-4 Neuroblastoma 135

11.2.6 Future Directions 136

11.2.7 Conclusion 136

References 137

11.3 High-Risk Neuroblastoma 138

11.3.1 Treatment Approach for High-Risk Disease 138

11.3.2 Induction Therapy 139

11.3.3 Local Control 141

11.3.4 Consolidation Therapy 142

11.3.5 Therapy of Minimal Residual Disease . . . 144

11.3.6 Conclusion 145

References 145

11.4 The Role of Surgery in the Treatment of Neuroblastoma 149

11.4.1 Introduction 149

11.4.2 History 149

11.4.3 Staging 151

11.4.3.1 Stage 1 151

11.4.3.2 Stage 2 152

11.4.3.3 Stage 3 152

11.4.3.4 Stage 4 153

11.4.4 Risk Status and Surgical Intervention ... 155

11.4.4.1 Low-Risk Patients 156

11.4.4.2 Intermediate Risk 156

11.4.4.3 High Risk 156

11.4.4.3.1 Gross Total Resection 156

11.4.4.3.2 Rationale for Gross Total Resection in High-Risk Patients 156

11.4.4.3.3 Local Control 157

11.4.5 Surgical Complications and Mortality . 157

11.4.6 Surgical Technique 158

11.4.6.1 Initial Biopsy 158

11.4.6.2 Cervical Lesions 159

11.4.6.3 Cervico-Thoracic Lesions 159

11.4.6.4 Mediastinal Tumors 159

11.4.6.5 Lesions in the Upper Abdomen and Retroperitoneum 159

11.4.6.6 Pelvic Tumors 159

11.4.7 Conclusion 160

References 161

11.5 Radiation Therapy 164

11.5.1 Background 164

11.5.2 Radiation Approach According to Risk Stratification 164

11.5.2.1 Low- and Intermediate-Risk Disease ... 164

11.5.2.2 Intermediate-Risk Disease 164

11.5.2.3 Stage-4S Disease 165

11.5.2.4 High-Risk Disease 165

11.5.3 Radiation Techniques 167

11.5.3.1 General Technical Considerations 167

11.5.3.2 Intraoperative Radiation Therapy 169

11.5.4 Side Effects of Radiation 170

11.5.5 Conclusion 171

References 171

11.6 Stem Cell Transplantation 173

11.6.1 Introduction 173

11.6.2 Autologous Transplant in Neuroblastoma 174

11.6.2.1 Children's Cancer Group 3891 174

11.6.2.2 Experimental HDC/SCR 175

11.6.3 PBSC Collection 177

11.6.3.1 Vascular Access 177

11.6.3.2 Collection 178

11.6.3.3 Techniques for Stem Cell Mobilization ... 178

11.6.3.4 Target Dose for PBSC Infusion 179

11.6.3.5 Processing and Storage of PBSC 180

11.6.3.6 Tumor Cell Purging 181

11.6.3.7 Storage 182

11.6.4 Conclusion 182

References 182

11.7 Minimal Residual Disease Measurement 185

11.7.1 Introduction 185

11.7.2 Techniques in the Detection of Tumor Cells in the Hematopoietic System 186

11.7.2.1 Histology/Cytology 186

11.7.3 Detection Methods for MRD 186

11.7.3.1 Immunocytology/

Immuno histochemistry 186

11.7.3.2 Automatic Immunofluorescence

Detection Techniques 187

11.7.3.3 Reverse Transcription-Polymerase

Chain Reaction 188

11.7.3.3.1 Real-Time Quantitative RT-PCR 188

11.7.3.3.2 Molecular Targets 188

11.7.3.3.3 Perspectives on Molecular Detection ... 188

11.7.4 Clinical Relevance of MRD 189

11.7.5 Future Directions 190

References 191

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