Pizzo & Poplack's Pediatric Oncology

Contents
SECTION 1
Biological Basis of Childhood Cancer
1 Epidemiology of Childhood Cancer 1
Michael E. Scheurer, Philip J. Lupo, Joachim Schüz,
and Logan G. Spector
Cancer Surveillance and Descriptive Epidemiology 1
Analytic Epidemiology 7
Summary and Future Considerations 12
2 Heredity and Childhood Cancer 15
David Malkin, Sharon E. Plon, Joshua D. Schiffman,
Christian P. Kratz, and Thierry Frebourg
Constitutional Chromosomal Abnormalities 15
Structural Chromosomal Abnormalities 16
Overgrowth Disorders and Imprinting Errors 17
Autosomal Dominant Disorders 18
Autosomal Recessive Disorders 27
Issue in Genetic Testing for the Pediatric
Oncology Patient 30
3 Molecular and Genetic Basis of Childhood
Cancer 34
Peter D. Aplan, Jack F. Shern, and Javed Khan
General Nature of Cancer-Associated Genetic
Aberrations 34
Comprehensive Analysis of the Cancer Genome 34
Germline Mutations 39
Somatically Acquired Chromosomal Aberrations
and Mutation 42
Gross Chromosomal Rearrangements 42
Oncogenic Consequences of Gross Chromosomal
Rearrangements—General Themes 43
Chromosomal Translocations Lead to Activation of
Proto-Oncogenes and Generation of Oncogenic
Fusion Genes 44
Chromosomal Deletion Leads to Inactivation of Tumor
Suppressor Genes 51
Gene Amplification 53
Point Mutations Leading to Gene Activation or
Inactivation 53
Comprehensive Genomic Studies of Pediatric
Tumors 54
Mechanisms of Malignant Cell Transformation, Growth,
and Clonal Expansion 57
Outlook for Molecularly Targeted Therapies 59
Summary 61
4 Biology of Childhood Cancer 66
Tanja Andrea Gruber and Elizabeth R. Lawlor
Gene Regulation 66
Protein Regulation 70
Signal Transduction 71
Cell Proliferation 74
Programmed Cell Death 76
Cancer Metabolism 79
Metastasis and the Tumor Microenvironment 82
5 Tumor Immunology of Childhood Cancer 87
Terry J. Fry, Paul M. Sondel, and Crystal L. Mackall
Overview of the Immune System 87
Modern Concepts of Immune Surveillance 91
T-Cell Recognition of Cancer 92
Innate Immune Cells and the Tumor
Microenvironment 93
Immune Function in Cancer Patients 93
Immunotherapy of Cancer 94
Summary and Future Directions 100
SECTION 2
Diagnosis and Evaluation of the Child
with Cancer
6 Clinical Assessment and Differential
Diagnosis of Suspected Childhood
Cancer 105
Wendy Allen-Rhoades and Charles Philip Steuber
Children at Risk 106
Time to Diagnosis 106
Differential Diagnosis 106
Establishing the Diagnosis 113
Summary 113
7 Pathology and Molecular Diagnosis of
Leukemias and Lymphomas 117
Elizabeth Margolskee, Gerald Benjamin Waith Wertheim, and
Richard C. Harvey
Introduction 117
Ancillary Studies 117
Lymphoblastic Leukemia 119
Myeloid Neoplasms 121
Mature Lymphoid Neoplasms 125
Histiocytic Disorders 128
8 Diagnostic Pathology of Pediatric Solid and
Central Nervous System Malignancies 131
Timothy J. Triche, Thomas G. P. Grünewald,
Jennifer Cotter, Matthew C. Hiemenz, Andrey Korshunov,
M. John Hicks, and Poul H. Sorensen
Introduction 131
Brief Pathologic Classification of Pediatric Solid
Tumors 133
Traditional Approaches to Childhood Solid Tumor
Diagnosis 134
Molecular Genetic Evaluation of
Childhood Cancer 146
Integrated Diagnostic Molecular Pathology of Pediatric
Solid Tumors 151
The Holistic Cancer Genome 169
DNA 169
RNA 170
Emerging Technologies for Diagnosis 170
The Future of Pediatric Cancer Diagnosis 172 9 Imaging Studies in the Diagnosis of
Childhood Cancer 184
Rajesh Krishnamurthy, Heike E. Daldrup-Link, Jeremy Y. Jones,
Stephan D. Voss, Adam J. Bobbey, Garima Suman, and
Ellen M. Chung
Relative Merits of Available Imaging Procedures 184
General Concepts of Pediatric Tumor Imaging 197
Future Directions 233
SECTION 3
Principles of Multimodal Therapy
10 General Principles of Chemotherapy 239
Elizabeth Fox, Susan M. Blaney, Lucas Moreno, Robin Norris,
Jeffrey M. Skolnik, Peter C. Adamson, and Frank M. Balis
Principles of Cancer Chemotherapy 239
Clinical Pharmacology of Anticancer Drugs 241
Alkylating Agents 255
Nonclassical Alkylating Agents 261
Antimetabolites 265
Purine Antimetabolites 268
Pyrimidine Antimetabolites 271
Topoisomerase Inhibitors 274
Tubulin Inhibitors 280
Miscellaneous Agents 282
Small-Molecule Pathway Inhibitors 287
Therapeutic Antibodies 291
Perspectives 293
11 General Principles of Cellular
Immunotherapy 303
Meenakshi G. Hegde, Shoba A. Navai, Sujith K. Joseph,
Andras Heczey, Stephen Gottschalk, Cliona M. Rooney, and
Malcolm K. Brenner
T Cells 303
Natural Killer Cells 318
gd Thymus-Derived T Cells 318
Invariant Natural Killer T Cells 318
Strategies to Improve Adoptive Cellular Therapies 319
Conclusions 321
12 General Principles of Targeted Therapy 327
Julia Glade Bender, Maria Luisa Sulis, and Malcolm A. Smith
Introduction 327
Basic Principles for the Clinical Development of
Molecularly Targeted Agents 327
Therapies Targeted to Apoptosis Pathways 338
Targeting Extracellular Survival Signaling Pathways 340
Targeting Development, Differentiation, and Other
Intracellular Processes 348
Targeting Angiogenesis 351
Conclusions 352
13 General Principles of Hematopoietic Stem
Cell Transplantation 362
Michael A. Pulsipher, Swati Naik, and Helen E. Heslop
Autologous Transplantation—High-Dose Chemotherapy
with Hematopoietic Stem Cell (HSC) Rescue 362
Allogeneic Transplantation 362
Allogeneic Hematopoietic Stem Cell Transplantation
Preparative Regimens 364
Transplantation for Leukemia 365
Transplantation for Hodgkin Lymphoma (HL) and
Non-Hodgkin Lymphoma (NHL) 372
Transplantation for Solid Tumors 374
Complications After Hematopoietic Stem Cell
Transplantation 375
Late Effects After Hematopoietic Stem Cell
Transplantation 378
Future Directions 379
14 General Principles of Radiation
Oncology 385
Colette J. Shen, Ralph P. Ermoian, Shannon E. Fogh,
Steve E. Braunstein, Kavita K. Mishra, Daphne A. Haas-Kogan,
and Stephanie A. Terezakis
Biologic Basis of Radiation Therapy 385
Physical Basis of Radiation Therapy 387
Interactions of Radiation Therapy and
Chemotherapy 393
Radiation Effects on Normal Tissues 394
15 General Principles of Surgery 405
Sanjeev A. Vasudevan, Richard S. Whitlock, Christopher B.
Weldon, and Jed G. Nuchtern
Preoperative Considerations for the Oncologist 405
Perioperative Considerations for the Oncologist 411
Minimally Invasive Surgery 414
SECTION 4
Management of Common Cancers of
Childhood
16 Acute Lymphoblastic Leukemia 419
M. Monica Gramatges, Maureen M. O’Brien, and Karen R. Rabin
Epidemiology 419
Genetic Risk Factors 420
Environmental Risk Factors 421
Pathogenesis 422
Classification of Acute Lymphoblastic Leukemia 422
Molecular Genomics of Acute Lymphoblastic
Leukemia 423
Pharmacogenetics 431
Clinical Presentation 432
Assessing Treatment Response 435
Prognostic Factors 435
Treatment 438
Treatment of Relapse 444
Late Effects of Treatment 445
Future Challenges 447
17A Acute Myeloid Leukemia and Myelodysplastic
Syndromes 454
Richard Aplenc, Caitlin W. Elgarten, John Kim Choi,
and Soheil Meshinchi
Historical Background and Definitions 454
Epidemiology of Pediatric Acute Myeloid Leukemia and
Myelodysplastic Syndrome 454
Biologic Basis of Acute Myeloid Leukemia and
Myelodysplastic Syndrome: From Normal Progenitors
to Leukemia 455
Methodologies for Classifying Myeloid
Malignancies 460
Defining Subtypes: Evolution of Diagnostic Classification
of Myeloid Malignancies 463
Clinical and Laboratory Presentation 467
Prognostic Factors and Implications of Risk Group
Stratification on Treatment 470
Evolution of Risk Adapted Therapy 474
Unique AML Subtypes and Settings 483
The Treatment of Relapsed or Refractory Acute
Myeloid Leukemia 484
Survivorship 486
17B Myeloproliferative Neoplasms
of Childhood 496
Rachel E. Rau and Mignon L. Loh
Chronic Myeloid Leukemia 496
Juvenile Myelomonocytic Leukemia 508
Polycythemia Vera and Essential Thrombocythemia 511 18 Hodgkin Lymphoma 517
Peter D. Cole, Rahul R. Parikh, and Kara M. Kelly
Biologic Considerations 517
Epidemiology, Pathogenesis & Pathology 518
Clinical Presentation 520
Treatment and Outcome 523
Nodular Lymphocyte Predominant Hodgkin
Lymphoma 528
Approach to Patients with Primary Refractory Disease or
Relapse of Hodgkin Lymphoma 530
Late Effects 531
Future Considerations 534
19 Malignant Non–Hodgkin Lymphomas in
Children 538
Thomas G. Gross, Kala Y. Kamdar, and Catherine M. Bollard
Non-Hodgkin Lymphoma Overview 538
NHL Cellular Classifications: Specific Biologic and Clinical
Considerations 540
Conclusions 550
Management Summary 550
20 Lymphoproliferative Disorders
and Malignancies Related to
Immunodeficiencies 554
David T. Teachey
Viral Pathogens and the Development of
Malignancies 554
Epstein–Barr Virus and Malignancies 554
Human herpesvirus-8 and Malignancies in
Immunodeficient Patients 555
Malignancies in Primary Immunodeficiencies 556
Secondary Immunodeficiency and Cancer 559
Malignancies in the Posttransplant Patient 560
Summary 565
21 Histiocytoses 568
Kenneth L. McClain, Carl E. Allen, Johannes H. Visser,
and M. John Hicks
Langerhans Cell Histiocytosis 568
Hemophagocytic Lymphohistiocytosis 573
Sinus Histiocytosis with Massive Lymphadenopathy
(Rosai–Dorfman Disease) 576
Juvenile Xanthogranuloma 576
Malignant Histiocytic Diseases 577
Summary 578
Management Summary 578
22A Gliomas, Ependymomas, and Other
Nonembryonal Tumors of the Central
Nervous System 582
D. Williams Parsons, Ian F. Pollack, Daphne A. Hass-Kogan,
Arnold C. Paulino, Stephen F. Kralik, Nilesh K. Desai, Adekunle
M. Adesina, and Murali M. Chintagumpala
Epidemiology 582
Inherited Syndromes Associated with Central Nervous
System Tumors 582
Ionizing Radiation and Central Nervous System
Tumors 583
Pathologic Classification of Central Nervous System
Tumors 584
Clinical Presentation 585
Neuroimaging in Pediatric Central Nervous
System Tumors: Current Status and Future
Directions 587
Neurosurgery: Diagnosis and Treatment 589
Radiation Therapy 591
Principles of Chemotherapy 593
Ependymoma 593
Low-Grade Gliomas 595
Tumors of the Optic Pathway 599
Supratentorial High-Grade Gliomas 600
Brainstem Gliomas 602
Craniopharyngioma 605
Choroid Plexus Neoplasms 607
Intramedullary Spinal Cord Tumors 608
Sequelae of Treatment 609
22B Tumors of the Central Nervous System:
Embryonal and Pineal Region Tumors 614
Annie Huang, Holly Lindsay, Benita Tamrazi,
Adekunle M. Adesina, Arnold C. Paulino, Ian F. Pollack,
Eric Bouffet, and Murali M. Chintagumpala
Embryonal Tumors 614
Medulloblastoma 614
Atypical Teratoid/Rhabdoid Tumor 624
Embryonal Tumors with Multilayered Rosettes 628
Other Rare Embryonal Tumors 631
Pineal Region Tumors 632
Germ Cell Tumors 637
23 Neuroblastoma 647
Julie R. Park, Michael D. Hogarty, Rochelle Bagatell, Gudrun
Schleiermacher, Yael P. Mossé, and John M. Maris
Epidemiology 647
Genetic Predisposition 647
Molecular Pathogenesis 649
Pathology 652
Clinical Presentation 653
Paraneoplastic Syndromes 653
Clinical and Laboratory Evaluation 654
Staging and Treatment Response 655
Prognostic Considerations 657
Principals of Initial Therapy 660
Late Effects 665
Future Considerations 666
24 Renal Tumors 673
Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Marry M.
van den Heuvel-Eibrink, Norbert Graf, Elizabeth A. Mullen, D.
Ashley Hill, John A. Kalapurakal, and Jeffrey S. Dome
Epidemiology 673
Genetics and Molecular Biology 673
Pathology 675
Clinical Presentation and Diagnostic Workup 677
Prognostic Factors 678
Treatment of Wilms Tumor 680
Clear Cell Sarcoma of the Kidney 687
Malignant Rhabdoid Tumor 688
Renal Cell Carcinoma 689
Congenital Mesoblastic Nephroma 689
25 Rhabdomyosarcoma 693
Corinne M. Linardic and Leonard H. Wexler
Epidemiology and Genetic Susceptibility 693
Molecular Biology 694
Animal Models 695
Pathology 695
Patterns of Spread and Clinical Presentation 698
Methods of Diagnosis 701
Staging 702
Prognostic Considerations 703
Treatment 705
Perspectives 715
26 Nonrhabdomyosarcoma Soft-Tissue
Sarcomas 721
Douglas S. Hawkins, Jennifer O. Black, Daniel Orbach, Thomas J.
Scharschmidt, Monika Scheer, Stephanie A. Terezakis, Rajkumar
Venkatramani, and Aaron R. Weiss
Epidemiology 721
Pathology 722
Clinical Presentation 723Prognostic Factors 724
Staging 724
General Treatment Considerations 724
Radiation Therapy 726
Chemotherapy 727
Selected Specific Diseases (Grouped First by Biologic
Potential and then in Alphabetical Order) 730
Intermediate, Locally Aggressive Soft-Tissue
Tumors 730
Intermediate, Rarely Metastasizing Soft-Tissue
Tumors 734
Future Directions 742
27 Ewing Sarcoma 747
Stephen L. Lessnick, Patrick J. Grohar, Steven G. DuBois,
Pancras C.W. Hogendoorn, Darin Davidson, Nadia Nicole Laack,
and Uta Dirksen
Nomenclature 747
Biology 747
Clinical Presentation and Staging 751
Pathology 753
Initial Treatment 754
Treatment 755
Management of Recurrent Disease 763
Late Effects 765
Summary and Conclusions 765
28 Osteosarcoma 770
Katherine A. Janeway, R. Lor Randall, and Richard Gorlick
Introduction 770
Clinical Presentation 770
Epidemiology 774
Pathology 776
Biology 778
Treatment 781
New Drugs 784
Follow-Up and Late Effects 788
29 Germ Cell Tumors 793
A. Lindsay Frazier, Thomas A. Olson, Dominik T. Schneider,
and James F. Amatruda
Nomenclature 793
Embryogenesis and Histogenesis of Gonadal
Tumors 793
Genetics and Molecular Biology 794
Pathology 795
Tumor Markers 798
Clinical Presentation, Staging, and Risk Assignment 799
Treatment Overview 802
Surgical Approach: Ovarian Tumors 803
Salvage Strategies 808
Toxicity and Late Effects 808
Future Considerations 809
30 Endocrine Tumors 811
Sogol Mostoufi-Moab, Rajkumar Venkatramani, Andrew J. Bauer,
and Steven G. Waguespack
Pituitary Tumors 811
Parathyroid Tumors 817
Thyroid Tumors 819
Gastroenteropancreatic Neuroendocrine Tumors 827
Adrenal Tumors 831
Pheochromocytoma and Paraganglioma 834
31 Liver Tumors 842
Howard M. Katzenstein, Dolores H. López-Terrada, Greg Tiao,
and Andras Heczey
Approach to Children with a Liver Mass 842
Hepatoblastoma 843
Staging, Pretreatment Extent of Tumor (Pretext) and
Current Risk Group Stratification of HB 849
Surgery in HCC 857
Hepatocellular Benign and Premalignant Epithelial
Biliary Epithelial and Mixed Biliary-Hepatocellular
Tumors 859
Mixed Epithelial/Mesenchymal or Uncertain Origin 859
Mesenchymal Tumors, Malignant 860
Metastatic and Other Malignant Tumors Involving
the Liver 863
32 Retinoblastoma 868
Ann-Marie Leahey, Dan S. Gombos, and Patricia Chevez-Barrios
Epidemiology 868
Anatomy 868
Genetics 869
Clinical Presentation 870
Diagnosis 871
Pathology 872
Metastasis and Recurrence 876
Trilateral Retinoblastoma and Other Tumors 877
Staging 877
Therapeutic Options 881
Immediate Future Directions 886
33 Rare Tumors 889
Rajkumar Venkatramani, Samara L. Potter, Kris Ann P. Schultz,
and Carlos Rodriguez-Galindo
Head and Neck 889
Chest 895
Abdomen 897
Genitourinary System/Pelvis 900
Skin 901
Bone Tumors 903
Conclusion 904
SECTION 5
Supportive Care of Children
with Cancer
34 Oncologic Emergencies 909
Susan R. Rheingold, Amanda M. Li, and Jason Lawrence
Freedman
Cardiothoracic Emergencies 909
Gastrointestinal Emergencies 913
Genitourinary Emergencies 917
Metabolic and Endocrine Emergencies 918
Neurologic Emergencies 923
Therapy-Associated Emergencies 930
Summary 933
35 Hematologic Supportive Care 937
Lani D. Lieberman, Amber M. Yates, and Jennifer Andrews
Anemia 937
Thrombocytopenia 939
Other Transfusion Products 942
Complications of Transfusion 944
Hematopoietic Colony-Stimulating Factors 950
36 Infectious Complications in Children with
Underlying Malignancy 955
Monica I. Ardura and Andrew Y. Koh
Host Defenses: Innate and Adaptive Immunity 955
Care of Febrile Cancer Patients 957
Empirical Antibacterial Treatment of Febrile
Neutropenic Patients 960
Antifungal Agents 966
Antiviral Agents 968
Anti-Pneumocystis Pneumonia Agents 971
Management of Unexplained Fever in the
Neutropenic Patient 971
Evaluation and Management of Documented
Infections 972
Prevention of Infection in Children with Cancer 988
Prophylactic Antibiotics 989Granulocyte Transfusions 992
Recombinant Human Cytokines 992
Adoptive T-Cell Therapy 994
Future Directions 994
37 Nursing Support of the Child
with Cancer 1002
Marilyn J. Hockenberry
Direct Patient Care Nursing Roles 1002
Advanced Practice Roles 1002
Research Roles 1003
Nursing Standards of Care 1003
Providing Expert Clinical Nursing Care 1003
Professional Development 1012
38 Nutritional Supportive Care 1014
Deena Altschwager and Alexandra N. Carey
Definition of Cancer Cachexia 1014
Obesity and the Pediatric Patient with Cancer 1015
The Population at Risk 1015
Etiology and Pathophysiology 1016
Clinical Assessment of Nutritional Status 1017
Nutrition Intervention Techniques 1019
Vitamins in Treating the Pediatric Patient with
Cancer 1021
Nutritional Concerns of Long-Term Survivors of
Childhood Cancer 1022
Conclusion 1022
39 Rehabilitation of the Child with Cancer 1024
Elaine Y. Tsao, David W. Pruitt, and Mary A. McMahon
Rehabilitation Problems 1024
Specific Childhood Cancers: Rehabilitation Issues 1029
Spinal Cord Tumors 1031
Bone Tumors 1033
Acute Lymphoblastic Leukemia 1034
40 Pain and Symptom Management 1038
Elliot J. Krane, Lori S. Wiener, Roy L. Kao, and Lonnie K. Zeltzer
Introduction 1038
Pain 1038
Etiologies of Cancer Pain 1045
Multimodal Management of Pain 1049
Pharmaceutical Management of Cancer-Related Pain
in Children 1050
Interventional Procedures for Pain Management 1057
Somnolence, Fatigue, Insomnia 1058
Summary 1062
41 Psychosocial Support for the
Child and Family 1067
Lori S. Wiener, Marieke Van Schoors, Maryland Pao,
and Melissa A. Alderfer
Principles and Essential Knowledge for Health
Professionals 1067
The Initial Diagnostic Period: A Time of Crisis 1067
Treatment: Reestablishing Equilibrium 1069
Relapses: A Second Crisis 1073
Survivorship 1076
Family Considerations 1077
Psychosocial and Psychiatric Interventions 1079
Final Word 1080
42 Educational Issues for Children with
Cancer 1083
Lisa M. Jacola, Lisa S. Kahalley, Stephanie K. Powell, Julie Baran,
and Robert B. Noll
School Reentry: Considerations and Stakeholders 1083
Evidence Base and Standards of Care 1084
Components of School Reentry Programs 1084
Special Education Services in Childhood Cancer
Survivors 1091
43 Palliative Care for the Child
with Cancer 1098
Jennifer M. Snaman, Jessica A. Casas, Tammy I. Kang, and
Joanne Wolfe
The Interdisciplinary Nature of Palliative Care 1099
Palliative Care for Children with Cancer 1099
Other Considerations at the End of Life 1116
SECTION 6
Other Considerations in Childhood
Cancer
44 Adolescents and Young Adults with Cancer
and Transitional Care to Adulthood 1123
David R. Freyer, Barbara Jones, Jennifer M. Levine,
Diana Jean Moke, and Michael Roth
Cancer Incidence and Survival Trends 1123
Treatment-Related Toxicity 1128
Clinical Trial Enrollment 1129
Psychosocial Issues 1130
Cancer Survivorship 1131
Conclusions 1132
Management Summary 1133
45 Late Effects of Childhood Cancer and its
Treatment 1135
Wendy Landier, Saro Armenian, M. Monica Gramatges,
Eric J. Chow, and Smita Bhatia
Burden of Morbidity 1137
Standardized Recommendations for Follow-Up of
Childhood Cancer 1138
Auditory Complications 1138
Neurocognitive Sequelae 1139
Cardiovascular Function 1139
Pulmonary Function 1140
Genitourinary Abnormalities 1141
Gastrointestinal Function 1142
Gonadal Function 1142
Other Endocrinologic Outcomes 1144
Growth Hormone Deficiency 1144
Obesity and Metabolic Syndrome 1144
Musculoskeletal and Related Tissues 1145
Subsequent Malignant Neoplasms 1146
Late Mortality Among Childhood Cancer
Survivors 1148
New Agents and New Potential
Late Effects 1148
Cancer Survivorship—Future Research
Opportunities 1149
46 Cancer Clinical Trials: Design, Conduct,
Analysis, and Reporting 1153
Arzu Onar-Thomas, Patricia Baxter, Lisa Bomgaars,
and Stacey L. Berg
Planning a Clinical Trial 1153
Feasibility Assessment 1159
Protocol Writing 1159
Regulatory Affairs 1160
Conduct of the Clinical Trial 1160
Analyzing Clinical Trial Data 1161
Reporting Results of Clinical Trials 1163
47 Ethical Considerations in Pediatric
Oncology 1165
Bryan Sisk, Avram E. Denburg, Abby R. Rosenberg, and
Eric Kodish
Informed Consent and Decision-Making 1165
Ethics of Research Involving Children with
Cancer 1167Privacy and Confidentiality 1175
Genetics and Genomics 1176
Population Inequities in Childhood Cancer Care and
Outcomes 1177
Caring for Health Care Providers 1179
Conclusion 1180
48 The Other Side of the Bed: What Providers
Can Learn from Listening to Patients and
Their Families 1185
Donna Ludwinski, Vikas Kundra, Nancy Goodman, Leona Knox,
and Elena Gerasimov
General Issues of Communication and Trust 1185
Major Events in the Care of Patients and
Their Families 1189
Conclusion 1196
49 Complementary and Integrative Therapies in
Pediatric Oncology 1197
Thomas Williams McLean and Susan F. Sencer
History 1197
Definitions 1197
Epidemiology 1197
Patients’ and Families’ Reasons for Using Complementary
and Integrative Therapies 1198
Talking with Patients and Families 1198
Integrative Therapy Modalities 1200
Biochemical Therapies 1200
Toxicities and Other Risks 1201
Lifestyle Therapy: Diet, Exercise, Environment, and
Mind–Body 1201
Environment 1202
Mind–Body 1202
Biomechanical Therapies 1202
Bioenergetic Therapies 1203
Summary 1204
50 Economic Issues in Pediatric Cancer 1207
Susan K. Parsons, Pei-Jung Lin, and K. Robin Yabroff
Patient–Physician Communication about Cost of
Cancer Care 1208
Methods of Economic Evaluation 1209
Financing Care 1212
Family Impact 1213
Conclusion 1215
51 Pediatric Cancer: Advocacy and Policy Issues
for Patients, Families, and Survivors 1218
Susan L. Weiner and Victoria Buenger
Landscape of the Childhood Cancer Advocacy
Community 1218
Advocates’ Central Policy Priorities 1219
Ongoing and Emerging Issues for Advocates 1224
52 Maximizing Safety in Cancer Treatment 1227
Brigitta U. Mueller and Amy L. Billett
Background 1227
Recognizing and Reporting of Problems 1229
Event Reporting 1230
Preventing Errors 1231
53 Pediatric Oncology in Low- and Middle-
Income Countries 1236
Joseph Lubega, Lulu F. Chirande, Kathy Pritchard-Jones,
and David G. Poplack
Epidemiology and Burden of Pediatric Cancer in
LMICs 1236
Health Systems and Sociocultural Barriers to Pediatric
Cancer Care in LMICs 1238
Shortage of Multispecialty Expertise for Pediatric Cancer
Care 1239
Diagnosis and Risk-Stratification Modalities of Pediatric
Cancer in LMICs 1239
Access to Cancer Treatment Modalities: Drugs, Pediatric
Surgery, and Radiotherapy 1240
Supportive Care for Children on Cancer Treatment in
LMICs 1240
Palliative Care for Children with Cancer in LMICs 1242
Survivorship Care for Children with Cancer in
LMICs 1242
Pediatric Oncology Research in LMICs 1242
Index 1245