Pediatric Oncology (eBook)

Foreword 6
Preface 8
Table of Contents 9
Contributors 12
1 Acute Leukemia 15
Chapter Overview 15
Introduction 16
Acute Lymphoblastic Leukemia 16
Etiology and Predisposing Factors 16
Molecular Genetic Abnormalities 16
Diagnosis 17
Classification Using Flow Cytometry 18
Treatment and Prognosis 18
Hematopoietic Stem Cell Transplantation 19
Supportive Care 21
Special Considerations for Infants 22
Mature B-Cell Leukemia 22
Clinical Features 22
Diagnosis 23
Treatment for Primary Disease 23
Treatment for Relapsed Disease 24
Myeloid Leukemia 24
Diagnosis 24
Supportive Care 25
Treatment for Primary Disease 26
Treatment for Relapsed Disease 27
Novel Therapies 27
HSCT 28
Long-Term Follow-Up 29
KEY PRACTICE POINTS 30
Suggested Readings 30
2 Hodgkin Lymphoma and Non-Hodgkin Lymphoma 32
Chapter Overview 32
Introduction 33
Hodgkin Lymphoma 33
Clinical Presentation 33
Pathology and Prognostic Factors 33
Diagnosis and Staging 34
Treatment 35
Therapy for Primary Disease 36
Therapy for Recurrent Disease 36
Long-Term Side Effects 37
Non-Hodgkin Lymphoma 38
Clinical Presentation 38
Pathology and Prognostic Factors 39
Diagnosis and Staging 39
Treatment 40
Treatment for Primary Disease 41
Therapy for Recurrent Disease 41
KEY PRACTICE POINTS 42
Suggested Readings 42
3 Brain Tumors: Diagnosis, Surgery and Radiotherapy, and Supportive Care 44
Chapter Overview 44
Introduction 45
Diagnosis 45
Clinical Presentation 45
Evaluation 47
Effect of Neurofibromatosis on Diagnosis 48
Neuropathology 49
Treatment 49
Neurosurgery 49
Hydrocephalus 50
Tumor Resection 51
Surgical Adjuncts 52
Radiotherapy 53
New Techniques for Focal Therapy 54
Craniospinal Radiotherapy 56
Chemotherapy 57
Follow-Up and Supportive Care 57
Neuropsychologic Evaluation 58
Late Neurologic Effects 60
Endocrine Evaluation 60
Other Multidisciplinary Care 61
KEY PRACTICE POINTS 61
Suggested Readings 62
4 Brain Tumors: Chemotherapy and Investigational Therapy 64
Chapter Overview 65
Introduction 65
Low-Grade Astrocytomas 65
Radiotherapy 66
Chemotherapy 67
Medulloblastoma and Other Embryonal Tumors 67
Preoperative Evaluation and Staging 68
Neurosurgery 68
Treatment of Average-Risk Medulloblastoma 69
Treatment of High-Risk Medulloblastoma and PNET 70
Treatment of Young Children with Embryonal Brain Tumors 70
High-Grade Gliomas 71
Surgery 71
Chemotherapy 73
Ependymoma 75
CNS Germ-Cell Tumors 76
Treatment of Germinoma 77
Treatment of Nongerminomatous Germ-Cell Tumor 77
Metastatic Brain Tumors 78
Recurrent Brain Tumors 78
Role of High-Dose Chemotherapy and Autologous Stem Cell Rescue 80
Complications and Long-term Care 81
KEY PRACTICE POINTS 81
Suggested Readings 82
5 Wilms’ Tumor 84
Chapter Overview 84
Introduction 85
Etiology 85
Associated Congenital Anomalies 85
Clinical Manifestations 86
Investigational Studies 86
Differential Diagnoses 87
Histologic Classification 87
Staging 87
Treatment 88
Surgery 88
Chemotherapy 88
Radiotherapy 91
Special Treatment Considerations 91
Inoperable and Bilateral Tumors 91
Recurrent, Progressive, and Resistant Tumors 91
Rare Metastases 92
Tumors Allied to or Previously ConsideredWilms’ Tumor 92
Rhabdoid Tumor of the Kidney 92
Congenital Mesoblastic Nephroma 92
Nephroblastomatosis 92
Side Effects of Therapy 92
Gastrointestinal System 93
Hepatic System 93
Cardiac System 93
Chest, Uterus, and Ovaries 93
Skelton 93
Follow-Up Evaluation 93
Prognosis 94
KEY PRACTICE POINTS 94
Suggested Readings 94
6 Neuroblastoma 96
Chapter Overview 96
Introduction 96
Clinical Presentation 97
Pathology, Pathogenesis, and Prognosis 99
Diagnosis and Staging 100
Treatment 102
Role of Bone Marrow Transplantation 104
Therapy for Recurrence 106
Neuroblastoma Screening 107
KEY PRACTICE POINTS 108
Suggested Readings 108
7 Soft-Tissue Tumors 110
Chapter Overview 110
Introduction 111
Incidence and Epidemiology 111
Disease Histiotypes and Chromosomal Abnormalities 111
RMS 112
NRSTS 112
Clinical Presentation 113
RMS 113
NRSTS 113
Aggressive Fibromatosis and Neurofibroma 113
Staging and Diagnostic Evaluation 114
RMS 114
NRSTS 115
Aggressive Fibromatosis and Neurofibroma 116
Treatment 116
RMS 116
Surgery 117
Radiotherapy 118
Chemotherapy 118
NRSTS 120
Aggressive Fibromatosis and Neurofibroma 121
Management of Relapse 121
KEY PRACTICE POINTS 122
Suggested Readings 122
8 Osteosarcoma 124
Chapter Overview 124
Introduction 124
Etiology 125
Clinical Manifestations 125
Histologic Varieties 125
Conventional Osteosarcoma 125
Surface Osteosarcoma 126
Biologic Behavior 126
Diagnostic Investigations 126
Definitive Diagnosis 127
Treatment for Primary Disease 127
Chemotherapy 127
Preoperative Intra-Arterial Chemotherapy 128
Postoperative Chemotherapy 128
Surgery 129
Treatment for Metastases 130
Pulmonary Metastases 130
Resistant or Recurrent Metastases 130
Investigational Therapies 131
Side Effects and Complications of Chemotherapy 131
Follow-Up 132
KEY PRACTICE POINTS 133
Suggested Readings 133
9 Ewing’s Sarcoma 135
Chapter Overview 135
Introduction 136
Etiology and Epidemiology 136
Presenting Signs, Clinical Features, and DiagnosticWork-Up 137
Pathology and Genetics 137
Prognostic Factors 137
Stage of Disease 138
Tumor Location 138
Tumor Size 138
Chromosomal Translocation 138
Surgical Margins 138
Response to Chemotherapy 139
Treatment 139
Chemotherapy 140
Immunotherapy 141
Therapy for Local Control 142
Surgery 143
Limb-Salvage Surgery: Endoprostheses and Allografts 144
Amputation or Rotationplasty 147
Surgical Aspects of Pelvic and Spinal Ewing’s Sarcomas 148
Radiotherapy 148
Timing of Treatment 149
Tumor Volume 149
Critical Structures in the Irradiated Volume 151
Radiation Dose 151
Radiation Fractionation 151
Toxicity 152
Treatment of Metastasis 152
KEY PRACTICE POINTS 153
Suggested Readings 153
10 Retinoblastoma 156
Chapter Overview 156
Introduction 156
Epidemiology and Genetics 157
Clinical Features 157
Workup 159
Treatment 162
Chemoreduction 162
Thermotherapy 164
Cryotherapy 164
Radiotherapy 164
Enucleation 165
Treatment of Metastatic Disease 166
Second Primary Tumors 166
KEY PRACTICE POINTS 166
Suggested Readings 167
11 Differentiated Thyroid Cancer 169
Chapter Overview 169
Introduction 169
Radiation-Induced Differentiated Thyroid Cancer 170
Regional Lymph Node Involvement 171
Pulmonary Metastases 171
Clinical Outcome and Mortality After Prolonged Follow-Up 172
Diagnosis, Treatment, and Surveillance 174
Case Example 1 176
Case Example 2 178
Case Example 3 178
Conclusions 178
KEY PRACTICE POINTS 179
Suggested Readings 179
12 Medullary Thyroid Carcinoma 181
Chapter Overview 181
Introduction 182
Histologic Features 182
Epidemiology and Tumor Subtypes 183
Sporadic Medullary Thyroid Carcinoma 183
Hereditary Medullary Thyroid Carcinoma 184
MEN2A 184
Variants of MEN2A 185
MEN2B 185
Clinical Features of MEN2-Associated Tumors 186
Evaluation and Management of Hereditary Medullary Thyroid Carcinoma 187
RET Proto-oncogene Mutations in MEN2 188
Genotype-Phenotype Correlations in MEN2 188
RET Proto-oncogene Testing 188
Use of Genetic Information 190
Highest Risk 190
High Risk 190
Intermediate Risk 191
Evaluation and Management of Pheochromocytoma and Hyperparathyroidism 191
Conclusions 192
KEY PRACTICE POINTS 192
Suggested Readings 192
13 Melanoma 194
Chapter Overview 194
Introduction 195
Diagnosis and Staging 195
Pathology 195
Primary Skin Tumor 195
Differential Diagnoses 197
Sentinel Lymph Nodes 199
Lymph Node Dissection 200
Immunohistochemisty 200
Surgical Treatment 201
Wide Local Excision 201
Lymph Node Mapping 202
Lymph Node Dissection 203
Evaluation for Metastasis 203
Blood Tests 203
Imaging Studies 203
Systemic Therapy 203
Adjuvant Therapy 203
Interferon 203
Biochemotherapy 204
Vaccine Therapies 204
Treatment of Measurable Disease 204
Follow-Up 204
KEY PRACTICE POINTS 205
Suggested Readings 205
14 Novel Therapeutic Approaches 208
Chapter Overview 208
Introduction 209
Realities of Pediatric Clinical Research 210
Stringent Regulatory Requirements 210
Slow Accrual 210
Need for More Biologic Correlates 211
Novel Therapies Used at M. D. Anderson 211
Hematologic Malignancies 212
Imatinib 213
Clofarabine 213
Solid Tumors 214
MTP-PE 214
Isotretinoin 214
Graft-Versus-Host Disease 215
Infliximab 216
Rapamycin 216
Pentostatin 217
Photopheresis 217
Is Research in Children Ethical? 217
When Should a Child Be Enrolled in a Clinical Trial? 219
Conclusions 219
KEY PRACTICE POINTS 219
Suggested Readings 220
15 Supportive Care: Myelosuppression 222
Chapter Overview 222
Introduction 222
Fever and Neutropenia 223
Antimicrobial Prophylaxis 226
Antibacterial Agents 226
Antiprotozoal Agents 226
Antiviral Agents 227
Hematologic Support 227
Anemia 227
Platelet Transfusions 228
Granulocyte Transfusions 229
Hematopoietic Growth Factors 229
KEY PRACTICE POINTS 230
Suggested Readings 230
16 Supportive Care: Symptom Control 232
Chapter Overview 233
Introduction 233
Chemotherapy-Induced Nausea and Vomiting 233
Pathophysiology 234
Risk Factors 234
Phases of Symptomatology 236
Treatment 237
Nutrition 237
Assessment 240
Enteral Feeding 241
Parenteral Feeding 242
Pain and Symptom Management 242
Pediatric Cancer Pain 244
Pathophysiologic Mechanisms of Pain 244
Pain and Symptom History 245
Assessment Tools 246
Synthesis of Symptom Diagnosis and Management Plan 246
Modalities of Symptom Control 246
Treatment Assessment 246
Analgesic Pharmacotherapy 247
Nonopioids and Adjuvant Analgesics 247
Opioids 247
Tolerance, Physical Dependence, and Addiction 248
Management of Side Effects 248
Principles of Analgesic Administration 249
Routes of Administration 249
Palliative Care 250
KEY PRACTICE POINTS 251
Suggested Readings 251
Appendix 16–1. Procedure for Determining the Emetogenicity of a Chemotherapy Regimen 253
Appendix 16–2. Eight-Step Process Involved in Total Parenteral Nutrition Administration 254
17 Behavioral Medicine in Cancer Care 258
Chapter Overview 258
Introduction 259
Supportive-Care Needs of Pediatric Patients and Family Members 259
Psychological- and Emotional-Support Interventions 260
Child-Life Specialists 261
Social Workers 261
Parent Consultants 261
Psychologists and Psychiatrists 261
Neuropsychologists 262
Education Staff 262
Language Assistants 262
Creative Arts Instructors 262
Clergy 263
Intensive Psychosocial-Support Interventions 263
Academic Interventions 264
Hospital-Based Schooling 264
Academic Program 264
ESL Program 265
Exercise and Physical Fitness 265
Support of Homebound and Community-School Programs 266
Neuropsychological Effects of Cancer 266
Role of Radiotherapy 266
Cognitive Remediation 267
Conclusions 268
KEY PRACTICE POINTS 268
Suggested Readings 269
18 The Adolescent and Young Adult Program 270
Chapter Overview 270
Introduction 271
Multidisciplinary Program Design 272
Improving Treatment Outcomes 272
Solid Tumors 272
Leukemia 273
Improving Quality of Life 274
Prior to Initiation of Therapy 274
Giving Patients Appropriate Control 275
Looking Beyond Therapy 275
During Therapy 276
Age-Appropriate Interaction and Support 276
Body Image and Relationships 276
Planning for the Future 277
Year-Round Social Activities 277
After Therapy 278
Monitoring for Recurrence and Secondary Malignancies 278
Addressing Long-Term Sequela 278
Ensuring Reintegration 279
Promoting Awareness of Issues Specific to Adolescents and Young Adults 280
Conclusions 280
KEY PRACTICE POINTS 280
Suggested Readings 281
Index 282

"11 Differentiated Thyroid Cancer (p. 155-156)

Chapter Overview

Thyroid nodules are relatively common in adult women but uncommon in adult men and in children and adolescents, and children are infrequently affected by differentiated thyroid cancer. When this cancer does occur in a child, the patient’s prognosis is generally favorable and he or she can expect a near-normal life span; however, it can prove to be a lethal neoplasm, especially in older patients and when distant metastases are present. The survival duration for children and adolescents with differentiated thyroid cancer is substantially long despite the fact that the disease presents with extensive morbid characteristics. The varied presentations and activities of differentiated thyroid cancer in children require speci?c diagnostic and treatment approaches and lifelong surveillance.

Introduction

Differentiated thyroid cancer, often simply called “thyroid cancer,” is an infrequent malignancy overall but the most common endocrine malignancy. At M. D. Anderson Cancer Center, less than 10% of all patients with differentiated thyroid cancer receive the diagnosis before 20 years of age. In children, differentiated thyroid cancer occurs more commonly as the papillary rather than the follicular variant, and it affects girls more often than boys.

Unlike in young adults, differentiated thyroid cancer presents in children with extensive disease bulk, including multifocal primary lesions, bilateral cervical lymph node metastases, and tumor invasion into the soft tissues of the neck. Diffuse pulmonary metastases may also be present in a small subset of children with cervical lymph node metastases. Children with differentiated thyroid cancer generally have a good prognosis despite the initial extent of disease (Harness et al, 1992; Hung and Sarlis, 2002). Nevertheless, disease- and treatment-related morbidity and mortality do occur; thus, a thoughtful, comprehensive initial evaluation and treatment plan must be coupled with lifelong surveillance in all cases.

Radiation-Induced Differentiated Thyroid Cancer

The risk for radiation-induced differentiated thyroid cancer is well documented. During the early decades of the twentieth century, low-dose irradiation to the head and neck was often used in the treatment of benign childhood conditions such as thymic enlargement, hemangioma, ringworm, and acne. The excess relative risk for radiation-induced differentiated thyroid cancer appears to depend on radiation dose and schedule as well as the patient’s age at the time of exposure.

The average time between irradiation and diagnosis of differentiated thyroid cancer is 10 years; accordingly, some cases of radiation-induced differentiated thyroid cancer will be diagnosed before the patient is 20 years old. There is no indication that radiationinduced differentiated thyroid cancer has a different clinical presentation and course than unirradiated cases of the disease. Increasing awareness of thyroid radiosensitivity, especially in children, has led to the virtual elimination of the use of irradiation for benign conditions; thus, low-dose radiation-induced differentiated thyroid cancer is expected to subside in the future."