Principles and Practice of Pediatric Oncology 7/e

Now thoroughly updated to include new advances in the field, Principles and Practice of Pediatric Oncology, 7th Edition
remains the gold standard text for the care and research of children with cancer. This authoritative reference is the
single most comprehensive resource on the biology and genetics of childhood cancer as well as its diagnosis, multimodal
treatment, as well as long-term management of young patients with cancer. Also addressed are a broad array of topics on
the supportive and psychosocial aspects of care of children and families. Covering virtually every aspect of the
breadth and depth of childhood cancer, this 7th Edition provides expert guidance on state-of-the-art, multidisciplinary
care for children and families.
Stay up to date with the most recent advances in the field with the contributions by new and returning contributors,
including the perspective from patients and parents in the chapter titled 밫he Other Side of the Bed.?
Chapters included on palliative care and education.


Table Of Contents

SECTION 1
BIOLOGICAL BASIS OF CHILDHOOD CANCER
1 Epidemiology of Childhood Cancer 1
Michael E. Scheurer, Philip J. Lupo, and Melissa L. Bondy
Cancer Surveillance and Descriptive Epidemiology 1
Analytic Epidemiology 5
Summary and Future Considerations 10
2 Childhood Cancer and Heredity 13
Sharon E. Plon and David Malkin
Constitutional Chromosomal Abnormalities 13
Structural Chromosomal Abnormalities 14
Overgrowth Disorders and Imprinting Errors 15
Autosomal Dominant Disorders 16
Autosomal Recessive Disorders 25
Issues in Genetic Testing for the Pediatric Oncology Patient 28
3 Molecular and Genetic Basis of Childhood Cancer 32
Peter D. Aplan, Jack F. Shern, and Javed Khan
Introduction 32
General Nature of Cancer-Associated Genetic Aberrations 32
Comprehensive Analysis of the Cancer Genome 32
Germline Mutations 38
Somatically Acquired Chromosomal Aberrations and Mutation 40
Gross Chromosomal Rearrangements 40
Oncogenic Consequences of Gross Chromosomal Rearrangements—General Themes 41
Chromosomal Translocations Lead to Activation of Proto-Oncogenes and Generation of Oncogenic Fusion Genes 41
Chromosomal Deletion Leads to Inactivation of Tumor Suppressor Genes 48
Gene Amplification 50
Point Mutations Leading to Gene Activation or Inactivation 51
Comprehensive Genomic Studies of Pediatric Tumors 52
Mechanisms of Malignant Cell Transformation, Growth, and Clonal Expansion 55
Outlook for Molecularly Targeted Therapies 57
Summary 58
Acknowledgments 58
4 Biology of Childhood Cancer 63
Christopher Denny, Daniel S. Wechsler, and Kathleen M. Sakamoto
Introduction 63
Signal Transduction 63
Gene Expression 66
Cell Cycle 70
Ubiquitin-Proteasome System 72
Programmed Cell Death 74
Tumor Microenvironment 76
5 Tumor Immunology and Pediatric Cancer 82
Terry J. Fry, Paul M. Sondel, and Crystal L. Mackall
Overview of the Immune System 82
Innate Immune Cells and the Tumor Microenvironment 82
T Lymphocytes and Co-Stimulation 85
B Lymphocytes 87
Natural Killer Cells 88
Immune Function in Cancer Patients 89
Modern Concepts of Immune Surveillance 89
Immunotherapy of Cancer 90
Summary and Future Directions 98
Acknowledgments 98
SECTION 2
DIAGNOSIS AND EVALUATION OF THE CHILD WITH CANCER
6 Clinical Assessment and Differential Diagnosis of the Child with Suspected Cancer 101
Wendy Allen-Rhoades and Charles P. Steuber
Introduction 101
Children at Risk 101
Time to Diagnosis 102
Differential Diagnosis 102
Establishing the Diagnosis 109
Summary 111
7 Pathology and Molecular Diagnosis of Leukemias and Lymphomas 113
Amy Heerema-McKenney, Michael L. Cleary, and Daniel A. Arber
Introduction 113
Specimen Processing 113
Use of Ancillary Studies 113
Acute Lymphoblastic Leukemia/Lymphoma (Precursor Lymphoid Neoplasms) 114
Acute Myeloid Leukemia 117
Myeloid Proliferations Related to Down Syndrome 122
Acute Leukemias of Ambiguous Lineage 123
Blastic Plasmacytoid Dendritic Cell Tumor 123
Myelodysplastic Syndromes and Myeloproliferative Neoplasms of Childhood 123
Hodgkin Lymphoma 124
Non-Hodgkin Lymphoma of Childhood 125
Other Hematopoietic Tumors 128
8 Diagnostic Pathology of Pediatric Malignancies 131
Timothy J. Triche, M. John Hicks, and Poul H. Sorensen
Overview 131
Childhood Tumor Diagnosis 136
Molecular Genetic Evaluation of Childhood Cancer 152
Morphologic Versus Molecular Diagnosis of Cancer in Children 163
Beyond Classification: Diagnosis to Direct Therapy 166
Genome-Wide Analysis for Diagnosis, Prognosis, and Therapeutic Target Identification 166
The Future of Pediatric Cancer Diagnosis 176

9 Imaging Studies in the Diagnosis and Management of Pediatric Malignancies 185
Rajesh Krishnamurthy, Heike E. Daldrup-Link, Jeremy Y. Jones, Stephan D. Voss, Geetika Khanna, Farahnaz Golriz, and
Robert P. Guillerman
Introduction 185
Relative Merits of Available Imaging Procedures 185
General Concepts of Pediatric Tumor Imaging 199
Future Directions 233
SECTION 3
PRINCIPLES OF MULTIMODAL THERAPY
10 General Principles of Chemotherapy 239
Peter C. Adamson, Susan M. Blaney, Rochelle Bagatell,Jeffrey M. Skolnik, and Frank M. Balis
Principles of Cancer Chemotherapy 239
Clinical Pharmacology of Anticancer Drugs 241
Alkylating Agents 247
Nonclassical Alkylating Agents 261
Antimetabolites 265
Purine Antimetabolites 268
Pyrimidine Antimetabolites 272
Topoisomerase Inhibitors 274
Tubulin Inhibitors 281
Small Molecule Pathway Inhibitors 283
Monoclonal Antibodies 288
Miscellaneous Agents 289
CNS Pharmacology of Anticancer Drugs 294
High-Dose Systemic Therapy for Meningeal and CNS Tumors 296
Perspectives 296
11 Molecularly Targeted Therapies and Biotherapeutics 316
Malcolm A. Smith
Introduction 316
Basic Principles for the Clinical Development of Molecularly Targeted Agents 316
Therapies Targeted to Apoptosis Pathways 327
Targeting Extracellular Survival Signaling Pathways 329
Targeting Janus Kinases (Jak) 334
Targeting the PI3K Pathway with Rapalogs and Other Inhibitors 335
Targeting Developmental Signaling Pathways 336
Targeting Mitotic Kinases and Kinesins 336
Targeting Histone Deacetylases 337
Targeting the Ubiquitin-Proteasome System 338
Targeting Angiogenesis 339
Conclusions 340
12 General Principles of Surgery 348
Christopher B. Weldon, Thomas E. Hamilton, and Robert C. Shamberger
Metabolic Response to Malignancy 348
Principles of Perioperative and Anesthetic Management 349
Management of Pheochromocytomas/Paragangliomas 352
Cancer Surgery 353
Preoperative Adjuvant Therapy 354
Minimally Invasive Surgery 359
13 General Principles of Radiation Oncology 362
Ralph P. Ermoian, Shannon E. Fogh, Steve Braunstein, Kavita K. Mishra, Larry E. Kun, and Daphne A. Haas-Kogan
Biological Basis of Radiation Therapy 362
Physical Basis of Radiation Therapy 365
14 Adoptive Cellular Immunotherapy 383
Stephen Gottschalk, Cliona M. Rooney, and Malcolm K. Brenner
Introduction 383
Natural Killer Cells 383
γδ Thymus-Derived T Cells 383
Invariant NKT Cells 384
T Cells 384
Combinatorial Cell Therapy 395
Conclusions 396
15 Adolescents and Young Adults with Cancer 401
Leonard S. Sender, Marcio H. Malogolowkin, and Keri B. Zabokrtsky
Adolescents and Emerging Adults 401
Aya Classifications Around the World 401
Cancers Seen in AYA Patients 402
Cancers that Highlight Important AYA Considerations 402
Clinical Trials and AYAs 411
Psychosocial Aspects of AYA Oncology 412
Oncofertility 413
Support Services 413
16 Hematopoietic Stem Cell Transplantation in Pediatric Oncology 419
Stephen Gottschalk, Swati Naik, Meenakshi Hegde, Catherine M. Bollard, Robert A. Krance, and Helen E. Heslop
Introduction 419
Allogeneic Transplantation 419
Autologous Transplantation 420
Source of HSCs 420
Transplant for Leukemia 421
Hodgkin Lymphoma and Non-Hodgkin Lymphoma 429
Transplantation for Solid Tumors 430
Complications After Stem Cell Transplantation 432
Regimen-Related Toxicity 434
Late Complications of Stem Cell Transplantation 435
Future Directions 436
17 Cancer Clinical Trials: Design, Conduct, Analysis, and Reporting 441
Susan G. Hilsenbeck, Lisa R. Bomgaars, and Stacey L. Berg
Planning a Clinical Trial 441
Managing the Clinical Trial 447
Reporting Results of Clinical Trials 450
18 Maximizing Safety in Cancer Treatment 452
Brigitta U. Mueller and Amy L. Billett
Introduction 452
Background 452
Recognizing and Reporting of Problems 454
Preventing Errors 455
SECTION 4
MANAGEMENT OF COMMON CANCERS OF CHILDHOOD
19 Acute Lymphoblastic Leukemia 463
Karen R. Rabin, Maria M. Gramatges, Judith F. Margolin, and David G. Poplack
Introduction 463
Epidemiology 463
Genetics 465
Pathogenesis 466
Classification of ALL 468
Molecular Genetics of ALL 469
Clinical Presentation 478
Prognostic Factors 481

Treatment 483
Treatment of Relapse 488
Late Effects of Treatment 491
Future Challenges 493
20 Acute Myeloid Leukemia and Myelodysplastic Syndromes 498
Robert J. Arceci and Soheil Meshinchi
Historical Background and Definitions 498
Epidemiology of Pediatric AML and MDS 498
Biological Basis of AML and MDS: From Normal Progenitors to Leukemia 499
Familial and Acquired Causes of MDS/AML in Children 500
Methodologies for Classifying Myeloid Malignancies 505
Defining Subtypes: Evolution of Diagnostic Classification of Myeloid Malignancies 508
AML in Children 514
Prognostic Factors and Implications of Risk Group Stratification on Treatment 516
Unique AML Subtypes and Settings 530
The Treatment of Relapsed and/or Refractory AML 533
Survivorship 535
21 Myeloproliferative Neoplasms of Childhood 545
Rachel Rau and Mignon L. Loh
Chronic Myeloid Leukemia 545
Juvenile Myelomonocytic Leukemia 559
PV and ET 563
22 Hodgkin Lymphoma 568
Monika L. Metzger, Matthew J. Krasin, John K. Choi, and Melissa M. Hudson
Epidemiology 568
Biology 569
Pathology 570
Clinical Presentation 572
Differential Diagnosis 572
Diagnostic Workup 572
Staging 573
Treatment 574
Nodular Lymphocyte-Predominant HL 581
Future Considerations 584
23 Malignant Non-Hodgkin Lymphomas in Children 587
Carl E. Allen, Kala Y. Kamdar, Catherine M. Bollard, and Thomas G. Gross
Introduction 587
Overall Incidence/Epidemiology 587
Precursor Lymphomas 589
Mature B-Cell Lymphomas 592
Burkitt Lymphoma 592
Diffuse Large B-Cell Lymphoma 596
Primary Mediastinal Large B-Cell Lymphoma 598
Rare Mature B-Cell Lymphomas 598
Anaplastic Large Cell Lymphoma 599
Mature T-Cell Lymphomas 600
Conclusions 600
Management Summary 601
24 Lymphoproliferative Disorders and Malignancies Related to Immunodeficiencies 604
Robert J. Hayashi, Birte Wistinghausen, and Bruce Shiramizu
Introduction 604
Viral Pathogens and the Development of Malignancies 604
Epstein-Barr Virus and Malignancies 604
HHV-8 and Malignancies in Immunodeficient Patients 605
Malignancies in Primary Immunodeficiencies 606
Secondary Immunodeficiency and Cancer 609
Malignancies in the Posttransplant Patient 610
Summary 614
25 Histiocytic Diseases 617
Kenneth L. McClain, Carl E. Allen, and M. John Hicks
Introduction 617
Langerhans Cell Histiocytosis 617
Hemophagocytic Lymphohistiocytosis 622
Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease) 624
Juvenile Xanthogranuloma 624
Malignant Histiocytic Diseases 625
Summary 626
Management Summary 626
26A Gliomas, Ependymomas, and Other Nonembryonal Tumors of the Central Nervous System 628
D. Williams Parsons, Ian F. Pollack, Daphne A. Hass-Kogan, Tina Y. Poussaint, Adekunle M. Adesina, and Murali M.
Chintagumpala
Epidemiology 628
Inherited Syndromes Associated with CNS Tumors 628
Other Factors Associated with CNS Tumors 629
Pathologic Classification of CNS Tumors 630
Clinical Presentation 631
Neuroimaging in Pediatric CNS Tumors: Current Status and Future Directions 633
Neurosurgery: Diagnosis and Treatment 636
Radiation Therapy 638
Principles of Chemotherapy 642
Ependymoma 643
Low-Grade Gliomas 645
Tumors of the Optic Pathway 649
Supratentorial High-Grade Gliomas 651
Brainstem Gliomas 653
Craniopharyngioma 657
Choroid Plexus Neoplasms 659
Intramedullary Spinal Cord Tumors 661
Sequelae of Treatment 662
26B Embryonal and Pineal Region Tumors 671
Murali M. Chintagumpala, Arnold Paulino, Ashok Panigrahy, Cynthia Hawkins, Andrew Jae, and D. Williams Parsons
Embryonal Tumors 671
Supratentorial PNETs 683
Atypical Teratoid/Rhabdoid Tumor 686
Pineal Region Tumors 688
Pineoblastomas 690
Germ Cell Tumors 691
27 Retinoblastoma 700
Richard L. Hurwitz, Carol L. Shields, Jerry A. Shields, Patricia Chévez-Barrios, Dan S. Gombos, Mary Y. Hurwitz, and
Murali M. Chintagumpala
Introduction 700
Epidemiology 700
Genetics 700
Clinical Presentation 702
Diagnosis 702
Pathology 705
Metastasis and Recurrence 710
Trilateral Retinoblastoma and Other Tumors 711
Staging 712
Therapeutic Options 715
Histopathologic Changes Associated with Treatment 722
Research Directions 722
28 Liver Tumors 726
Rebecka L. Meyers, Angela D. Trobaugh-Lotrario, Marcio H. Malogolowkin, Howard M. Katzenstein, Dolores H. López-
Terrada, and Milton J. Finegold
Historical Context 726
Differential Diagnosis 726
Epithelial Tumors 727

Mixed Epithelial/Mesenchymal or Uncertain Origin 744
Mesenchymal Tumors: Malignant 745
Mesenchymal Tumors: Malignant/Other 746
Metastatic and Other Malignant Liver Tumors 748
29 Renal Tumors 753
Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, D. Ashley Hill, John A. Kalapurakal, and Jeffrey S. Dome
Introduction 753
Epidemiology 753
Genetics and Molecular Biology 753
Pathology 755
Clinical Presentation and Diagnostic Workup 757
Prognostic Factors 758
Treatment of Wilms Tumor 759
Clear-Cell Sarcoma of the Kidney 766
Malignant Rhabdoid Tumor 767
Renal Cell Carcinoma 768
Congenital Mesoblastic Nephroma 768
Acknowledgments 768
30 Neuroblastoma 772
Garrett M. Brodeur, Michael D. Hogarty, Rochelle Bagatell, Yael P. Mossé, and John M. Maris
Introduction 772
Incidence and Epidemiology 772
Genetic Predisposition 773
Molecular Pathogenesis 773
Pathology 777
Clinical Presentation 777
Clinical and Laboratory Evaluation 779
Staging and Treatment Response 780
Prognostic Considerations 782
Principles of Initial Therapy 785
Treatment of Recurrent Disease 790
Late Effects 792
Future Considerations 792
Acknowledgments 792
31 Rhabdomyosarcoma 798
Leonard H. Wexler, Stephen X. Skapek, and Lee J. Helman
Epidemiology and Genetic Susceptibility 798
Molecular Biology 799
Animal Models 799
Pathology 800
Patterns of Spread and Clinical Presentation 802
Methods of Diagnosis 806
Staging 807
Prognostic Considerations 808
Treatment 810
Perspectives 821
32 The Nonrhabdomyosarcoma Soft Tissue Sarcoma 827
Sheri L. Spunt, Lynn Million, and Cheryl Coffin
Introduction 827
Epidemiology 827
Pathology 828
Clinical Presentation 828
Prognostic Factors 829
Staging 830
General Treatment Considerations 830
Radiation Therapy 832
Chemotherapy 834
Selected Specific Diseases (Listed by Biologic Potential and in Alphabetical order) 836
Intermediate, Locally Aggressive Soft Tissue Tumors 836
Intermediate, Rarely Metastasizing Soft Tissue Tumors 842
Malignant Soft Tissue Tumors 845
Late Effects of Therapy 851
Future Directions 851
33 Ewing Sarcoma 855
Douglas S. Hawkins, Bernadette M. D. Brennan, Tobias Bölling, Darin J. Davidson, Uta Dirksen, Steven G. DuBois, Pancras
C. W. Hogendoorn, and Stephen L. Lessnick
Introduction and Epidemiology 855
Nomenclature 855
Biology 855
Clinical Presentation and Staging 859
Pathology 861
Initial Treatment 863
Recurrent Disease: Novel Treatment Strategies 871
Late Effects 872
Summary and Conclusions 872
34 Osteosarcoma 877
Richard Gorlick, Katherine Janeway, and Neyssa Marina
Introduction 877
Clinical Presentation 877
Epidemiology 881
Pathology 884
Biology 885
Treatment 889
Future Directions 895
Follow-Up and Late Effects 896
35 Germ Cell Tumors 899
A. Lindsay Frazier, Thomas A. Olson, Dominik T. Schneider, Elizabeth J. Perlman, and James F. Amatruda
Nomenclature 899
Embryogenesis and Histogenesis of Gonadal Tumors 899
Genetics and Molecular Biology 900
Pathology 902
Tumor Markers 905
Clinical Presentation and Staging 906
Treatment Overview 909
Ovarian Tumors 914
Testicular Tumors 915
Extragonadal Tumors 915
Salvage Strategies 916
Toxicity and Late Effects 916
Future Considerations 917
36 Endocrine Tumors 919
Steven G. Waguespack, Winston W. Huh, and Andrew J. Bauer
Introduction 919
Pituitary Tumors 919
Parathyroid Tumors 925
Thyroid Tumors 926
Gastoenteropancreatic Neuroendocrine Tumors 933
Adrenal Tumors 936
Pheochromocytoma and Paraganglioma 939
37 Rare Pediatric Tumors 946
Carlos Rodriguez-Galindo, Wayne L. Furman, and Alberto S. Pappo
Introduction 946
Cancer of the Aerodigestive Tract and Related Anatomical Sites 946
Cancer of the Lungs, Heart, and Thymus 952
Cancer of the Digestive Tract 954
Cancer of the Pancreas 957
Rare Cancers of the Genitourinary System 958
Cancer of the Skin 959
Other Rare Pediatric Cancers 961

SECTION 5
SUPPORTIVE CARE OF CHILDREN WITH CANCER
38 Oncologic Emergencies 967
Jason L. Freedman, Susan R. Rheingold, and Michael J. Fisher
Cardiothoracic Emergencies 967
Gastrointestinal Emergencies 971
Genitourinary Emergencies 975
Neurologic Emergencies 976
Vascular, Metabolic, and Endocrine Emergencies 982
Therapy-Associated Emergencies 988
39 Hematologic Supportive Care for Children with Cancer 992
Jennifer Andrews, Susan A. Galel, Wendy Wong, and Bertil Glader
Anemia 992
Thrombocytopenia 994
Acknowledgment 1007
40 Infectious Complications in Pediatric Cancer Patients 1010
Monica I. Ardura and Andrew Y. Koh
Host Defenses: Innate and Adaptive Immunitiy 1010
Care of Febrile Cancer Patients 1013
Empirical Antibacterial Treatment of Febrile, Neutropenic Patients 1015
Antifungal Agents 1021
Antiviral Agents 1024
Anti-Pneumocystis Pneumonia Agents 1027
Management of Unexplained Fever in the Neutropenic Patient 1027
Evaluation and Management of Documented Infections 1029
Prevention of Infection in Children with Cancer 1046
Prophylactic Antibiotics 1046
Immunization 1048
Granulocyte Transfusions 1050
Recombinant Human Cytokines 1050
Adoptive T-Cell Therapy 1052
Future Directions 1053
41 Nutritional Supportive Care 1058
Sonia A. Ballal, Lori J. Bechard, and Christopher Duggan
Introduction 1058
Definition of Cancer Cachexia 1058
Obesity and the Pediatric Patient with Cancer 1059
The Population at Risk 1059
Etiology and Pathophysiology 1059
Clinical Assessment of Nutritional Status 1060
Nutrition Intervention Techniques 1062
Vitamins in Treating the Pediatric Patient with Cancer 1064
Nutritional Concerns of Long-Term Survivors of Childhood Cancer 1065
Conclusion 1065
42 Pain and Symptom Management 1067
Elliot J. Krane, Jacqueline Casillas, and Lonnie K. Zeltzer
Overview of Childhood Cancer 1067
What is Pain 1067
Pain in Children: How Does it Differ from that in Adults 1069
Pain in Children: Can it be Quantitated 1070
Cancer Pain in Children 1072
Treatment of Pain in Pediatric Cancer Patients 1072
Drugs for Pain Management 1076
Interventional Procedures for Pain Management 1083
Side Effects and Symptoms in Pediatric Cancer Patients 1085
Summary 1092
43 Nursing Support of the Child with Cancer 1094
Marilyn J. Hockenberry, Nancy E. Kline, and Cheryl Rodgers
Direct Patient Care Nursing Roles 1094
Advanced Practice Roles 1094
Research Roles 1095
Nursing Standards of Care 1095
Providing Expert Clinical Nursing Care 1095
Professional Development 1105
44 Rehabilitation of the Child with Cancer 1108
David W. Pruitt, Mary A. McMahon, and Susan D. Apkon
Rehabilitation Problems 1110
Specific Childhood Cancers: Rehabilitation Issues 1113
45 Psychiatric and Psychosocial Support for the Child and Family 1124
Lori S. Wiener, Maryland Pao, Melissa A. Alderfer
Principles and Essential Knowledge for Health Professionals 1124
Initial Diagnostic Period: A Time of Crisis 1124
Relapses and Recurrences: A Second Crisis 1131
Survivorship 1134
Family Considerations 1135
Psychosocial and Psychiatric Interventions 1137
Final Word 1138
46 The Other Side of the Bed: What Caregivers Can Learn from Listening to Patients and Their Families 1141
Stephen J. Chanock, Vikas Kundra, Nancy Goodman, and Mary D. Singer
Introduction 1141
General Issues of Communication and Trust 1141
Major Events in the Care of Patients and their Families 1148
Conclusion 1154
Acknowledgments 1155
47 Ethical Considerations in Pediatric Oncology 1156
Steven Joffe, Jennifer Kesselheim, and Susan Shurin
Introduction 1156
Informed Consent 1156
Ethics of Research Involving Human Participants 1158
Ethical Issues at the End of Life 1163
Privacy and Confidentiality 1165
Genetics and Genomics 1166
Financial Incentives and Conflict of Interest 1167
SECTION 6
OTHER ISSUES ARISING AT DIAGNOSIS, DURING TREATMENT, AND AFTER CESSATION OF THERAPY
48 Late Effects of Childhood Cancer and its Treatment 1173
Wendy Landier, Saro H. Armenian, Anna T. Meadows, and Smita Bhatia
Burden of Morbidity 1173
Knowledge about Past Diagnosis and Treatment 1173
Standardized Recommendations for Follow-up of Childhood Cancer 1173
Auditory, Ocular, Oral, and Dental Complications 1178
Neurocognitive Sequelae 1179
Cardiovascular Function 1180

Pulmonary Function 1181
Genitourinary Abnormalities 1182
Gastrointestinal Function 1182
Thyroid Abnormalities 1183
Gonadal Function 1183
Growth 1185
Obesity 1186
Musculoskeletal and Related Tissues 1186
Subsequent Malignant Neoplasms 1189
Late Mortality Among Childhood Cancer Survivors 1191
Cancer Survivorship—Future Research Opportunities 1191
49 Educational Issues for Children with Cancer 1197
Laurie D. Leigh, Heather M. Conklin, and Jane E. Schreiber
The Importance of School Reentry Intervention 1197
Phases of School Reentry 1198
Conclusion 1208
Acknowledgments 1209
50 Palliative Care for the Child with Cancer 1210
Christina K. Ullrich, Barbara M. Sourkes, and Joanne Wolfe
Palliative Care: A Philosophy of Care 1210
Palliative Care for Children with Cancer 1211
51 Economic Issues in Pediatric Cancer 1228
Susan K. Parsons, Pei-Jung Lin, and Joshua T. Cohen
Patient-Physician Communication about Cost of Cancer Care 1229
Methods of Economic Evaluation 1229
Financing Care 1234
Family Impact 1235
Conclusion 1236
52 Pediatric Cancer Policy and Case Advocacy on Insurance, Education, and Employment 1238
Susan L. Weiner and Gilbert P. Smith
Part I: National Childhood Cancer Advocacy and Policy Priorities 1238
Part II: Case Advocacy For Individual Patients and Survivors 1242
Conclusion 1246
53 Complementary and Alternative Medical Therapies in Pediatric Oncology 1247
Thomas W. McLean and Kathi J. Kemper
Introduction 1247
Definitions 1247
Epidemiology 1247
Patients’ and Families’ Reasons for Using Complementary and Alternative Medicine 1247
Cam Therapies 1249
Ethical and Legal Considerations 1253
Summary 1254
54 Pediatric Oncology in Countries with Limited Resources 1256
Raul C. Ribeiro, Guillermo L. Chantada, Ramandeep S. Arora, Federico Antillon, Mariana Kruger, and Ronald D. Barr
Background 1256
Epidemiology of Pediatric Cancer Worldwide 1256
International Disparities and Barriers to Progress 1258
Pediatric Oncology Research in LMIC 1260
Index 1267

Supportive care is covered broadly and specifically in contexts such as emergencies, infectious disease, and
nutrition.
Benefit from completely new and updated information throughout.
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Gain a thorough understanding of every aspect of pediatric oncology, with comprehensive information regarding basic
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coverage of each pediatric malignancy.
Collaborate more effectively with others on the cancer care team to enhance quality-of-life issues for patients and
families.
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cooperative clinical trial groups and consortia.
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