Oncology of Infancy and Childhood: Expert Consult

Cover......Page 1
ISBN: 9781416034315......Page 2
Copyright Page......Page 3
Contributors......Page 6
Preface......Page 13
I - Biology of Cancer......Page 14
Epidemiology of Leukemia in Childhood......Page 16
Acute Lymphoblastic Leukemia......Page 17
Time Trends......Page 19
Leukemia and Cancer in the Families of Children with Leukemia......Page 20
Genetic Polymorphisms......Page 21
Residence in Areas with High Population Mixing......Page 22
Immunizations......Page 23
Seasonal Variations in Childhood Leukemia Onset......Page 24
Radiation Exposure......Page 25
Hydrocarbons and Solvents......Page 26
Maternal Diet and Vitamin Supplement Use During Pregnancy......Page 27
Maternal Age and Birth Order......Page 28
Congenital Anomalies......Page 29
REFERENCES......Page 30
Angiogenesis......Page 40
Molecular Players That Regulate Angiogenesis......Page 41
Inhibitors of Angiogenesis......Page 42
Hematologic Malignancies Are Angiogenic......Page 43
Myelodysplastic Syndrome......Page 44
Targeting the Vascular Endothelial Growth Factor Pathway......Page 45
Antiangiogenic Chemotherapy......Page 46
Platelets and Angiogenesis......Page 47
Capacity of Platelets to Regulate Angiogenesis......Page 48
REFERENCES......Page 49
Molecular Basis of Human Malignancy......Page 54
Cell-Intrinsic Events......Page 55
Telomeres and Telomerase in Human Cancer......Page 56
p53.......Page 57
Transformation......Page 58
Ras......Page 59
Myc......Page 60
Genetic Instability......Page 61
Cancer Cell Invasion and Metastasis......Page 62
REFERENCES......Page 63
Targeted Approaches to Drug Development......Page 70
Inhibitors of Microtubule Formation......Page 71
Toxicity Acceptable with Curative Therapy......Page 72
What is Targeted Therapy?......Page 73
Advantages of Targeted Therapy......Page 74
Synthetic Lethal or Empirical Track......Page 75
Target Expression......Page 76
Loss-of-Function Genetic Alterations......Page 77
Gain-of-Function Experiments......Page 79
Drugs......Page 80
Targeted Therapy: Lessons Learned from Adult Oncology......Page 83
Imatinib in Chronic Myelogenous Leukemia......Page 84
Beyond Chronic Myelogenous Leukemia and Gastrointestinal Stromal Tumors......Page 86
Epithelial Growth Factor Receptor Inhibition for Non–Small Cell Lung Cancer......Page 87
Rituximab Therapy for Non-Hodgkin’s Lymphoma......Page 88
Bevacizumab and Colorectal Cancer......Page 89
Heat Shock Protein 90 Inhibitors......Page 90
Histone Deacetylase Inhibitors......Page 91
Rarity of Pediatric Cancer......Page 92
Fms-Like Tyrosine Kinase 3 and Acute Leukemias......Page 93
Sonic Hedgehog Signaling and Medulloblastoma......Page 94
Transcription Factors and Pediatric Cancer......Page 96
Antidisialoganglioside and Neuroblastoma......Page 98
Insulin-like Growth Factor Receptor Signaling and Pediatric Solid Tumors......Page 99
REFERENCES......Page 100
Cytogenetic and Molecular Pathology of Pediatric Cancer......Page 112
Need for Sufficient Viable Tumor......Page 113
Unpredictable Tumor Cell Growth in Culture......Page 118
Complex Karyotype......Page 119
Technical Limitations in Detecting Aberrations......Page 120
Highly Combinatorial Modifications of Fluorescence in Situ Hybridization.......Page 121
Maximizing Data Yield from Individual Fluorescence in Situ Hybridization Probes for Rearrangements.......Page 123
General Applications of Polymerase Chain Reaction–Based Methods......Page 124
Specificity of Reverse Transcriptase Polymerase Chain Reaction.......Page 125
Quantitative Polymerase Chain Reaction......Page 126
GENOMIC MECHANISMS IN PEDIATRIC TUMORS......Page 127
Causes and Predisposing Factors for Chromosomal Translocations......Page 129
Chromosomal Rearrangements Involving Transcription Factor Genes......Page 131
Chromosomal Rearrangements Involving Protein Tyrosine Kinase Genes......Page 132
BIOLOGIC BASIS FOR SPECIFICITY OF BALANCED CHROMOSOMAL REARRANGEMENTS: DIAGNOSTIC RELEVANCE......Page 134
Ewing’s Sarcoma......Page 135
Rhabdomyosarcoma......Page 136
Clear Cell Sarcoma: Malignant Melanoma of Soft Parts......Page 138
Desmoplastic Small Round Cell Tumor......Page 139
Infantile Fibrosarcoma......Page 140
Neuroblastoma......Page 141
Pediatric Renal Cell Carcinomas with Xp11 or 6p21 Translocations......Page 142
Mesoblastic Nephroma......Page 143
CNS Tumors......Page 144
Hodgkin’s Lymphoma......Page 145
Nodular Lymphocyte-Predominance Hodgkin’s Lymphoma......Page 146
Anaplastic Large Cell Lymphoma......Page 147
Acute Lymphoblastic Leukemia......Page 149
Intralocus IG and TCR Gene Rearrangements......Page 150
Interlocus IG and TCR Gene Rearrangements and Translocations......Page 151
MLL Translocations.......Page 152
FLT3 Mutations.......Page 153
Acute Myeloid Leukemia......Page 154
t(15;17).......Page 156
t(6;9).......Page 157
Therapy-Related Acute Myeloid Leukemias and Myelodysplastic Syndromes......Page 158
Juvenile Myelomonocytic Leukemia......Page 159
Transient Abnormal Myelopoiesis and Acute Megakaryoblastic Leukemia of Down Syndrome......Page 160
RAS Mutations......Page 161
RELEVANCE OF GENETIC ABERRATIONS FOR TARGETED THERAPIES......Page 162
Imatinib Mesylate......Page 164
REFERENCES......Page 165
II - Pediatric Cancer Therapeutics......Page 185
Chemotherapy in the Pediatric Patient......Page 188
RATIONALE FOR CHEMOTHERAPY OPTIMIZATION......Page 189
Absorption Changes......Page 195
Hepatic Metabolism......Page 196
Choice of Starting Dose......Page 197
Coadministration of Other Chemotherapeutic Drugs......Page 198
Coadministration of Nonchemotherapeutic Drugs......Page 199
Coadministration of Complementary and Alternative Medicine......Page 200
Thiopurine S-Methyltransferase......Page 202
CYP2B6......Page 203
CYP2D6......Page 204
CYP3A4 and CYP3A5......Page 205
ABCB1......Page 206
Conventional Method: Body Surface Area–Based Dosing......Page 209
Therapeutic drug monitoring......Page 210
Pharmacokinetic alterations......Page 211
Drug scheduling and administration sequencing......Page 212
REFERENCES......Page 213
Immunotherapy of Cancer......Page 222
Monoclonal Antibodies......Page 223
T Cells......Page 225
γδ T Cells......Page 226
Dendritic Cells......Page 227
TUMOR TARGET ANTIGENS......Page 228
Normal Proteins Expressed in Immune-Privileged Sites......Page 229
Rationale and Physiology......Page 230
Immunization to Tumor Antigens......Page 231
The Interferons......Page 233
Interleukin-2......Page 234
MONOCLONAL ANTIBODIES......Page 235
Naked Monoclonal Antibodies......Page 236
Immunotoxins......Page 237
Radioimmunoconjugates......Page 238
Adoptive T-Cell Therapy......Page 239
Adoptive T-Cell Therapy to Treat Pediatric Malignancies......Page 240
The Graft Versus Leukemia Reaction......Page 241
Nonmyeloablative Transplants for Leukemia and Lymphoma......Page 243
Donor Lymphocyte Infusions......Page 244
Allogeneic Natural Killer-Cell Infusions......Page 245
CHALLENGES AND FUTURE DIRECTIONS......Page 246
REFERENCES......Page 247
Pediatric Radiation Oncology......Page 254
THE PHYSICAL BASIS OF RADIATION THERAPY......Page 255
Clonogenic Survival Curves......Page 256
Radiation Interactions with Chemotherapeutic Agents......Page 257
Vascular Endothelial Growth Factor Receptor Inhibitors......Page 258
Combining Molecularly Targeted Therapies with Conventional Antineoplastic Treatments......Page 259
Modern Treatment Approaches......Page 260
Intensity-Modulated Radiation Therapy......Page 261
Carbon Ions......Page 262
Clinical Applications......Page 263
Sequelae of Treatment......Page 265
REFERENCES......Page 266
Pediatric Surgical Oncology......Page 270
ANESTHESIA IN A PATIENT WITH AN ANTERIOR MEDIASTINAL MASS......Page 271
The Five Principles......Page 273
Small Specimen Biopsies......Page 274
Fine Needle Aspiration and Core Needle Biopsy......Page 275
Large Specimen Biopsies......Page 277
Extremity Tumors......Page 278
Wilms’ Tumor......Page 279
Neuroblastoma......Page 280
Hepatoblastoma......Page 282
Osteosarcoma, Ewing’s Sarcoma......Page 283
Surgical Principles......Page 284
Endoprostheses......Page 286
Distal Femur and Proximal Tibia......Page 287
Rotationplasty......Page 289
Pelvis......Page 290
Proximal Humerus......Page 292
Outcomes......Page 293
MANAGEMENT OF PULMONARY METASTASIS IN PEDIATRIC SOLID TUMORS......Page 294
The Four Principles......Page 295
Metastasis Localization......Page 296
Differentiated Thyroid Cancers......Page 297
Hepatoblastomas......Page 298
Sarcomas......Page 299
REFERENCES......Page 300
III - Hematologic Malignancy......Page 307
Acute Lymphoblastic Leukemia......Page 310
Immunophenotype......Page 311
B-precursor cell Acute Lymphoblastic Leukemia......Page 312
CLINICAL MANIFESTATIONS......Page 314
Bone Marrow......Page 315
Bone and Joint Manifestations......Page 316
Aplastic Anemia, Myelodysplasia, and Myeloproliferative Disorders......Page 317
Immunophenotype......Page 318
Minimal Residual Disease.......Page 319
Risk-Adapted Therapy......Page 320
Phases of Therapy......Page 321
Central Nervous System Treatment......Page 322
Continuation Therapy......Page 323
Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia......Page 324
Metabolic Complications......Page 325
Acute Neurologic Toxicity......Page 326
Bony Morbidity......Page 327
RELAPSED ACUTE LYMPHOBLASTIC LEUKEMIA......Page 328
Unrelated and Autologous Stem Cell Transplantation......Page 329
REFERENCES......Page 330
Myeloid Leukemia, Myelodysplasia, and Myeloproliferative Disease in Children......Page 344
Epidemiology and Etiology......Page 345
Clonal Origin of Myeloid Leukemia Cells......Page 346
Transformation of Stem Cells with Self-Renewal Capacity......Page 347
Molecular Genetics......Page 348
Class I Mutations......Page 349
Translocations Involving the Retinoic Acid Receptor-α.......Page 351
Type 2 Mutations......Page 353
Morphology and Cytochemistry......Page 354
M0: Acute Myeloblastic Leukemia with Minimal Differentiation......Page 359
M5: Acute Monocytic Leukemia......Page 361
World Health Organization Classification......Page 362
Remission Induction......Page 363
Current U.S. Trials......Page 364
Supportive Therapy at Diagnosis and During Therapy......Page 365
Bleeding Complications......Page 366
Chemotherapy Complications......Page 367
Demographic Risk Factors......Page 368
Prognosis in Relapsed or Refractory Disease......Page 369
Antibody Therapy with Gemtuzumab Ozogamicin......Page 370
Apoptosis inhibitors......Page 371
Arsenic trioxide......Page 372
Hematopoietic Stem Cell Transplantation......Page 373
Pathobiology......Page 374
Clinical Presentation......Page 375
Treatment......Page 376
Pathophysiology......Page 377
Clinical Presentation......Page 378
Pathobiology......Page 379
Chronic Myelogenous Leukemia Caused by the BCR-ABL Fusion Gene......Page 380
Clinical Presentation......Page 381
Tyrosine Kinase Inhibitors......Page 382
Hematopoietic Stem Cell Transplantation......Page 383
Polycythemia Vera......Page 384
Essential Thrombocythemia......Page 385
Agnogenic Myeloid Metaplasia with Myelofibrosis......Page 386
REFERENCES......Page 387
Infant Leukemias......Page 416
RISK FACTORS......Page 417
biology of Mixed Lineage Leukemia translocations......Page 418
Clinical and Biologic Features......Page 419
Prognostic Factors and Outcomes......Page 420
Toxicity and Central Nervous System–Directed Therapy......Page 421
Association with Down Syndrome......Page 422
Modulators of Glucocorticoid Resistance......Page 423
REFERENCES......Page 424
Malignant Lymphomas and Lymphadenopathies......Page 430
Histopathology and Classification......Page 431
Classic Hodgkin’s Lymphoma......Page 432
Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma......Page 433
Epidemiology and Causative Factors......Page 434
Cellular Microenvironment: Cytokines and Chemokines......Page 437
Clinical Characteristics......Page 438
Clinical Evaluation and Staging Procedures......Page 441
Prognostic Factors—Stratification of Treatment......Page 444
Radiotherapy......Page 445
Combined-Modality Chemotherapy and Radiotherapy......Page 446
Relapsed Patients......Page 453
Late Effects......Page 455
Definition......Page 458
Immunophenotype......Page 459
Role of T-Cell Receptor Translocations.......Page 460
NOTCH1 Activation.......Page 462
HOX11(TLX1), HOX11L2(TLX3), and HOXA9 Homeobox Genes.......Page 463
Cell Cycle Regulators: p15INK4B, p14ARF, and p16INK4A Inactivation and Cyclin D2 Overexpression.......Page 464
Morphology.......Page 465
Role of Epstein-Barr Virus......Page 466
Centroblastic Variant.......Page 467
Anaplastic Large Cell Lymphoma......Page 468
Time Trends in Incidence Rates......Page 469
Familial Predisposition......Page 470
Infections......Page 471
Clinical Characteristics......Page 472
Diagnosis and Staging......Page 477
Staging Classification......Page 478
Clinical Evaluation and Staging Procedures......Page 479
Emergencies......Page 480
Prevention and Treatment of Acute Tumor Cell Lysis Syndrome......Page 481
Acute Renal Dysfunction and Uremia......Page 482
Chemotherapy......Page 483
Extracompartmental Therapy......Page 485
Chemotherapy......Page 486
Extracompartmental Therapy......Page 489
Chemotherapy......Page 491
Incomplete Tumor Regression, Second-Look Surgery, and Monitoring of Response......Page 492
Treatment of Children and Adolescents with Rare Non-Hodgkin’s Lymphoma Subtypes......Page 493
Treatment of Relapse......Page 494
Prognostic Factors......Page 495
Post–Solid Organ Transplantation PTLD Versus Post-HSCT PTLD......Page 496
Treatment......Page 497
LYMPHADENOPATHY......Page 498
Approach to the Patient......Page 499
MEDIASTINAL MASSES......Page 500
References......Page 501
IV - Solid Tumors......Page 519
Neuroblastoma......Page 522
Development of the Sympathetic Nervous System......Page 523
Hereditary predisposition......Page 525
MYCN Amplification......Page 526
Chromosome 17q Gain......Page 527
Neurotrophin Expression in Neuroblastoma......Page 528
Apoptosis Pathways......Page 529
Histopathology......Page 530
CLINICAL PRESENTATION......Page 532
Paraneoplastic Syndromes......Page 533
Risk Stratification......Page 534
Clinical Variables......Page 536
Treatment of Low-Risk Disease......Page 537
Treatment of Intermediate-Risk Disease......Page 538
Local Control......Page 539
Consolidation Therapy......Page 540
Treatment of Minimal Residual Disease......Page 541
Immunotherapy......Page 542
REFERENCES......Page 543
Pediatric Renal Tumors......Page 554
Staging......Page 555
Epithelial Patterns.......Page 556
Focal and Diffuse Anaplasia.......Page 557
Nephrogenic Rests and Nephroblastomatosis......Page 558
Classic Pattern.......Page 559
Clear Cell Sarcoma of the Kidney Versus Wilms’ Tumor.......Page 560
Differential Diagnosis......Page 561
Malignant Rhabdoid Tumor Versus Wilms’ Tumor.......Page 562
Xp11.2 Translocation Renal Cell Carcinomas......Page 563
Oncocytic Renal Carcinomas in Neuroblastoma Patients......Page 564
Epidemiology......Page 565
β-Catenin and WTX......Page 566
WT2—The 11p15 Locus......Page 567
Clinical Presentation and Diagnostic Evaluation......Page 568
Radiation Therapy......Page 569
Chemotherapy......Page 571
Anaplastic Wilms’ Tumor......Page 572
Late Effects of Wilms’ Tumor Treatment......Page 573
Treatment......Page 574
Clinical Presentation and Diagnostic Evaluation......Page 575
Molecular Biology and Genetics......Page 576
Treatment......Page 577
FUTURE DIRECTIONS......Page 578
REFERENCES......Page 579
Retinoblastoma......Page 588
CLINICAL PRESENTATION......Page 589
DIAGNOSIS......Page 590
Screening All Children......Page 591
Screening Children with Increased Risk for Retinoblastoma......Page 592
Routes of Extraocular Spread......Page 593
Histopathologic Features that Predict Extraocular Spread......Page 594
Relationship to Retinoblastoma......Page 595
Gene and Protein Structure......Page 596
Gene Mutations in RB1......Page 597
GENETIC DIAGNOSIS......Page 598
Management of Retinoblastoma......Page 599
Systemic Workup......Page 600
General Principles in Treating Intraocular Retinoblastoma......Page 601
Cryotherapy......Page 602
Radiotherapy for Retinoblastoma......Page 603
Chemotherapy for Retinoblastoma......Page 605
REFERENCES......Page 609
Tumors of the Brain and Spinal Cord......Page 614
EPIDEMIOLOGY......Page 615
Neural Tube......Page 617
Cerebellar Cortex......Page 618
Neurofibromatosis Type 1......Page 619
Gorlin’s Syndrome......Page 620
Lhermitte-Duclos Disease, Cowden’s Syndrome, and PTEN Mutation......Page 621
CONCEPTUAL ORGANIZATION OF PEDIATRIC BRAIN TUMORS......Page 622
Obstructive Hydrocephalus and Raised Intracranial Pressure......Page 624
Neuroimaging......Page 625
Neurosurgery......Page 628
Acute Management Issues......Page 629
Perioperative Issues......Page 631
Stereotactic Radiotherapy.......Page 632
Chemotherapy......Page 633
Blood-Brain Barrier......Page 634
Small-Molecule Inhibitors......Page 635
Gliomas......Page 636
Imaging and Histology.......Page 637
Management.......Page 638
Clinical Presentation.......Page 640
Management.......Page 641
Management.......Page 642
Management.......Page 643
Imaging and Histology.......Page 644
Pilomyxoid Astrocytomas......Page 645
Ganglioglioma and Glial-Neuronal Tumors......Page 646
Imaging and Histology.......Page 647
Subependymal Giant Cell Astrocytomas (SEGAs)......Page 648
Management.......Page 649
Lipoastrocytomas.......Page 650
Imaging and Histology.......Page 651
Management.......Page 652
Clinical Presentation.......Page 653
Management.......Page 654
Management.......Page 655
Clinical Presentation.......Page 656
Imaging and Histology.......Page 657
Prognosis.......Page 658
Management.......Page 659
Embryonal Tumors......Page 660
Clinical Presentation.......Page 661
Imaging and Histology.......Page 662
Management.......Page 664
Historical Perspective......Page 665
Radiation Therapy......Page 666
Prognosis......Page 667
Management.......Page 668
Management.......Page 669
Imaging and Histology.......Page 670
Ependymoblastomas......Page 671
Prognosis.......Page 672
Imaging and Histology.......Page 673
Imaging and Histology.......Page 674
Choroid Plexus Tumors......Page 675
Imaging and Histology.......Page 676
Clinical Presentation.......Page 677
Imaging and Histology.......Page 678
Management.......Page 679
Imaging and Histology.......Page 680
Prognosis.......Page 681
Management.......Page 682
Specific Management Issues in Infants and Young Children......Page 683
Infant Central Nervous System Primitive Neuroectodermal Tumors and Pineoblastoma......Page 684
Infant Glioma......Page 685
Imaging and Histology.......Page 686
Management.......Page 687
Hamartomas......Page 688
Astroblastomas......Page 689
Imaging and Histology.......Page 690
Imaging and Histology.......Page 691
Clinical Presentation.......Page 692
Management.......Page 693
Imaging and Histology.......Page 694
Late Effects of Radiation......Page 695
PALLIATIVE CARE......Page 698
REFERENCES......Page 699
Hepatoblastomas and Other Liver Tumors......Page 734
STEM CELL ORIGINS OF HEPATOBLASTOMA......Page 735
GENETIC PREDISPOSITION AND LIVER TUMORIGENESIS......Page 736
PREMATURITY AS A RISK FACTOR......Page 738
STAGING......Page 739
ACQUIRED GENETIC CHANGES IN HEPATOBLASTOMA......Page 740
TREATMENT: CHEMOTHERAPY......Page 741
SURGICAL ASPECTS OF LIVER TUMORS......Page 745
LESS COMMON MALIGNANT TUMORS OF THE LIVER......Page 746
BENIGN TUMORS OF THE LIVER......Page 747
REFERENCES......Page 748
Rhabdomyosarcoma......Page 756
Pathologic Classification of Rhabdomyosarcoma......Page 757
Li-Fraumeni Syndrome......Page 758
Costello Syndrome......Page 759
Comparative Genomic Hybridization Analyses of Copy Number Changes in Rhabdomyosarcoma......Page 760
Molecular Genetics of Chromosomal Translocations in Alveolar Rhabdomyosarcoma......Page 762
Gene Amplification in Rhabdomyosarcoma......Page 763
Oncogene and Tumor Suppressor Gene Mutations in Rhabdomyosarcoma......Page 764
Myogenic Pathways in the Tumorigenesis of Rhabdomyosarcoma......Page 765
Role of Insulin-like Growth Factors in Rhabdomyosarcoma......Page 766
Metastatic Pathways in Rhabdomyosarcoma......Page 767
Activation of the Shh Signaling Pathway......Page 769
Models in Other Species......Page 771
Gene Expression Profiling with Microarrays......Page 772
Detection of Minimal Disseminated Rhabdomyocarcoma......Page 773
Clinical Evaluation......Page 774
Histology......Page 775
Metastases at Diagnosis......Page 776
Cyclophosphamide......Page 777
Doxorubicin......Page 778
Irinotecan......Page 779
Treatment Strategies......Page 780
Surgery......Page 781
Radiation Therapy......Page 782
Infants and Toddlers......Page 783
Parameningeal Tumors......Page 784
Late Effects......Page 785
REFERENCES......Page 786
Nonrhabdomyosarcomas and Other Soft Tissue Tumors......Page 796
introduction......Page 797
Epidemiology......Page 798
Presentation and Evaluation......Page 800
Staging and Grading......Page 801
Treatment......Page 802
Chemotherapy......Page 803
ADIPOCYTIC TUMORS......Page 804
Infantile Myofibroma/Myofibromatosis and Hemangiopericytoma......Page 805
Specific Forms of Fibrosarcoma......Page 806
Low-Grade Fibromyxoid Sarcoma......Page 807
Myxofibrosarcoma......Page 808
Inflammatory Myofibroblastic Tumor......Page 809
Sporadic Leiomyosarcoma......Page 810
Giant Cell Angioblastoma......Page 813
Kaposi Sarcoma......Page 814
Mesenchymal Chondrosarcoma......Page 815
Synovial Sarcoma......Page 816
Clear Cell Sarcoma......Page 818
Desmoplastic Small Round Cell Tumor......Page 820
Angiomatoid Fibrous Histiocytoma......Page 821
Epithelioid Sarcoma......Page 822
Gastrointestinal Stromal Tumor......Page 823
Malignant Peripheral Nerve Sheath Tumors......Page 824
Undifferentiated Sarcoma/High-grade Undifferentiated Polymorphous Sarcoma......Page 825
REFERENCES......Page 826
Ewing’s Sarcoma......Page 842
EPIDEMIOLOGY......Page 843
Chromosomal Rearrangements in Ewing’s Sarcoma......Page 844
Wild-type EWS Protein......Page 845
EWS/FLI and Other TET/ETS Fusions in Ewing’s Sarcoma......Page 846
Ewing’s Sarcoma Cell of Origin......Page 848
EWS/FLI Target Genes......Page 849
Cooperative Pathways in Ewing’s Sarcoma Oncogenesis......Page 850
Clinical Presentation......Page 851
Imaging Features......Page 853
Pathologic Diagnosis......Page 854
PROGNOSTIC FACTORS......Page 855
Local Control......Page 857
Early Improvements with Vincristine, Actinomycin D, Doxorubicin, and Cyclophosphamide......Page 859
Addition of Ifosfamide and Ifosfamide plus Etoposide to VACA-Based Therapy......Page 861
Dose-Intensified VACA/IE Regimens......Page 862
Ewing’s Sarcoma of the Spine......Page 863
Role of Surgery and Radiation......Page 864
Role of High-Dose Therapy with Hematopoietic Stem Cell Rescue......Page 865
Systemic Chemotherapy......Page 866
LATE EFFECTS IN PATIENTS TREATED FOR EWING’S SARCOMA......Page 867
REFERENCES......Page 869
Osteosarcoma......Page 884
EPIDEMIOLOGY......Page 885
CAUSE......Page 886
Radiologic Evaluation......Page 888
Biopsy......Page 890
Pathology......Page 891
Staging......Page 894
Prognostic Factors......Page 895
Genetic Alterations......Page 896
Retinoblastoma......Page 897
p53......Page 899
MET......Page 900
Insulin-like Growth Factor......Page 901
Determinants of Metastasis......Page 902
Biologic Markers of Response to Chemotherapy......Page 903
Chemotherapy and Outcome......Page 904
Ifosfamide and Etoposide......Page 907
Neoadjuvant Chemotherapy......Page 908
Current Approach to Therapy......Page 909
Treatment of Initially Metastatic Osteosarcoma......Page 910
Treatment of Recurrent Osteosarcoma......Page 911
Complications of Therapy......Page 912
REFERENCES......Page 914
Pediatric Germ Cell Tumors......Page 924
Primordial Germ Cell Migration......Page 925
Testicular Germ Cell Tumors......Page 926
Histopathology......Page 928
Ovarian Teratoma......Page 929
Histopathology......Page 930
Seminoma......Page 931
Choriocarcinoma......Page 932
Incidence......Page 933
Possible Environmental Causes......Page 936
Cryptorchidism and Testicular Cancer......Page 937
Adolescent and Adult Malignant Germ Cell Tumors......Page 938
Testicular Germ Cell Tumors......Page 939
Sacrococcygeal Germ Cell Tumors......Page 940
Evaluation for Metastatic Disease......Page 941
Tumor Markers......Page 942
Surgical Approach to Sacrococcygeal Tumors......Page 944
Evaluation of Retroperitoneal Nodes in Pediatric Testicular Germ Cell Tumors.......Page 945
Prognostic Factors at Diagnosis......Page 946
Seminoma and Dysgerminoma......Page 947
Factors that Predict Relapse.......Page 948
History of Use of Chemotherapy In Men with Testicular Cancer.......Page 949
Treatment of Pediatric Germ Cell Tumors in the United States......Page 950
Treatment of Pediatric Germ Cell Tumors in the United Kingdom......Page 952
Dose of Bleomycin in Treatment of Pediatric Germ Cell Tumors......Page 953
Mature and Immature Teratomas......Page 954
Sacrococcygeal Tumors......Page 955
Men with Testicular Cancer......Page 956
Radiotherapy......Page 957
Prospects for Targeted Therapy of Germ Cell Tumors......Page 958
Risk of Cardiovascular Disease......Page 959
Gonadal Function.......Page 960
REFERENCES......Page 961
Histiocytoses......Page 976
Types of Dendritic Cells......Page 977
Incidence and Etiology......Page 978
Bone......Page 979
Skin......Page 980
Risk Sites......Page 981
Therapy of Single-System Disease......Page 982
Therapy of Multisystem Disease......Page 983
Refractory Langerhans Cell Histiocytosis......Page 984
Juvenile Xanthogranuloma......Page 985
Origins of Macrophages......Page 986
Nonsyndromic Familial Hemophagocytic Lymphohistiocytosis......Page 987
Hemophagocytic Lymphohistiocytosis Associated with Other Genetic Syndromes......Page 988
Macrophage Activation Syndrome......Page 989
Clinical Features......Page 990
Infection-Associated Hemophagocytic Lymphohistiocytosis.......Page 992
Hematopoietic Cell Transplantation......Page 993
REFERENCES......Page 994
Rare Tumors of Childhood......Page 1002
Presentation......Page 1003
Epidemiology......Page 1004
Clinical Presentation and Staging......Page 1005
BREAST TUMORS......Page 1006
Bronchial Adenomas......Page 1007
Bronchogenic Carcinoma......Page 1008
Other Pulmonary Tumors......Page 1009
Gastrointestinal Stromal Tumors in Adults......Page 1010
Pediatric Gastrointestinal Stromal Tumors......Page 1011
CARCINOID......Page 1012
COLORECTAL CARCINOMA......Page 1013
Treatment......Page 1014
OVARIAN TUMORS......Page 1016
TUMORS OF THE CERVIX AND VAGINA......Page 1017
MELANOMA......Page 1018
Other Factors......Page 1019
Treatment and Outcome......Page 1020
REFERENCES......Page 1021
V - Supportive Care......Page 1027
Diagnostic Imaging in the Evaluation of Childhood Cancer......Page 1030
Computed Tomography......Page 1031
Positron Emission Tomography......Page 1033
Staging Considerations......Page 1034
Oligodendroglioma......Page 1035
Central Neurocytoma......Page 1036
Infratentorial Tumors......Page 1037
Cerebellar Astrocytoma......Page 1038
Ependymoma......Page 1039
Metastatic Disease......Page 1040
Spinal Cord Tumors......Page 1044
Thyroid and Parathyroid Tumors......Page 1045
Mediastinal Masses and Tumors......Page 1046
Lymphoma......Page 1047
Thymoma......Page 1048
Tracheobronchial Tree Masses......Page 1049
Posterior Mediastinal Masses......Page 1051
Ewing’s Sarcoma......Page 1055
Pulmonary Metastases......Page 1057
Hepatoblastoma......Page 1058
Hepatocellular Carcinoma......Page 1059
Mesenchymal Hamartoma......Page 1061
Focal Nodular Hyperplasia......Page 1063
Spleen Tumors......Page 1064
Pancreatoblastoma......Page 1065
Pancreatic Sarcomas......Page 1066
Alimentary Tract Tumors......Page 1067
Wilms’ Tumor......Page 1069
Clear Cell Sarcoma......Page 1071
Renal Cell Carcinoma......Page 1072
Rare Renal Tumors......Page 1073
Rhabdomyosarcomas......Page 1075
Neuroblastoma......Page 1076
Ovarian Germ Cell Tumors......Page 1080
Testicular Germ Cell Tumors......Page 1081
Sacrococcygeal Germ Cell Tumors......Page 1082
MUSCULOSKELETAL NEOPLASMS......Page 1083
Osteosarcoma......Page 1084
Ewing’s Sarcoma......Page 1085
Other Bone Tumors......Page 1086
Synovial Sarcoma......Page 1088
Infantile (Desmoid-type) Fibromatosis......Page 1089
Acute Lymphoblastic Leukemia......Page 1090
Childhood Acute Myelogenous Leukemia......Page 1091
Lymphoma......Page 1092
Staging......Page 1094
Non-Hodgkin’s Lymphoma......Page 1095
Sites of Relapse......Page 1098
IMAGING TREATMENT COMPLICATIONS......Page 1099
NEW IMAGING TECHNIQUES......Page 1101
Magnetic Resonance Spectroscopy......Page 1102
Targeted Contrast Agents......Page 1103
REFERENCES......Page 1104
Infectious Diseases in Pediatric Cancer......Page 1112
Fungi......Page 1113
Physical Defense Barriers......Page 1114
Defects in Cell-Mediated Immunity......Page 1115
Fever and Neutropenia......Page 1116
Antibiotic Management of a Neutropenic Patient Who Becomes Febrile......Page 1117
Modification of Antibiotic Therapy During the Course of Granulocytopenia......Page 1118
Empirical Antifungal or Antiviral Therapy During Prolonged Granulocytopenia......Page 1119
Oropharyngeal Candidiasis (Thrush) and Candida Esophagitis......Page 1121
Chronic Disseminated (Hepatosplenic) Candidiasis......Page 1122
Infections Caused by Aspergillus Species......Page 1123
Infection by the Varicella-Zoster Virus......Page 1124
Other Viral Infections......Page 1125
REFERENCES......Page 1126
Oncologic Emergencies......Page 1134
Overview......Page 1135
Incidence......Page 1136
Clinical Manifestations and Treatment......Page 1137
Fluids and Alkalinization......Page 1138
Hyperuricemia......Page 1139
Definition......Page 1141
Clinical Presentation......Page 1142
Treatment......Page 1143
ANTERIOR MEDIASTINAL MASSES......Page 1144
Evaluation and Imaging......Page 1147
Chemotherapy......Page 1149
Clinical Studies......Page 1150
Vesicant Extravasation......Page 1152
REFERENCES......Page 1153
Nursing Care of Patients with Childhood Cancer......Page 1158
OVERVIEW OF THE PEDIATRIC ONCOLOGY NURSE’S ROLE......Page 1159
The Nurse’s Relationship with Patients, Families, and Other Providers......Page 1160
Patient- and Family-Centered Care......Page 1161
Educating Patients and Families......Page 1162
Informing Patients and Families of the Diagnosis......Page 1163
Surgery......Page 1164
Chemotherapy......Page 1165
Preprocedure Phase......Page 1166
Complementary and Integrative Therapies......Page 1167
Neutropenia......Page 1168
Fatigue......Page 1169
Pain......Page 1170
Managing Pain and Stress during Invasive Procedures......Page 1171
Central Venous Access Devices......Page 1172
The Emotional Impact of Transitioning from Treatment......Page 1173
NURSING CARE OF CHILDHOOD CANCER SURVIVORS......Page 1174
Follow-up Nursing Care......Page 1175
Recurrence......Page 1176
End-of-Life and Palliative Care......Page 1177
Outpatient, Home, and Hospice Care......Page 1178
ETHICAL NURSING PRACTICE......Page 1179
FUTURE TRENDS IN ONCOLOGY NURSING......Page 1180
Cancer Treatment and the Roles of Nurses......Page 1181
Nursing Research......Page 1182
REFERENCES......Page 1183
Palliative Care in Pediatric Oncology......Page 1190
INTEGRATING PALLIATIVE CARE AT THE TIME OF DIAGNOSIS......Page 1191
Advantages of Early Integration of Palliative Care......Page 1192
Creating a Plan for Care Based on Goals......Page 1193
Talking with Children About Palliative Care......Page 1194
The Spiritual Assessment......Page 1197
INTERDISCIPLINARY CARE......Page 1198
Hospice Services......Page 1199
SYMPTOM-DIRECTED THERAPY......Page 1200
Dyspnea......Page 1201
Constipation......Page 1203
Fatigue......Page 1204
Anxiety......Page 1205
Anemia and Bleeding......Page 1206
Swallowing Impairment......Page 1207
Talking with Parents About What to Expect......Page 1208
Bereavement Care for Families......Page 1209
REFERENCES......Page 1210
Symptom Management in Children with Cancer......Page 1216
Epidemiology......Page 1217
Pathophysiology......Page 1218
Self-Report Instruments......Page 1219
Behavioral Observation Scales......Page 1220
Nonopioid Analgesics......Page 1221
Developmental Pharmacology......Page 1222
Hepatic Failure.......Page 1223
Fentanyl.......Page 1224
Rectal Route.......Page 1225
Breakthrough Pain......Page 1226
Opioid-induced Neurotoxicity......Page 1227
Invasive Approaches to Pain Management......Page 1228
Psychological and Nonpharmacologic Approaches to Pain......Page 1229
Mucositis......Page 1230
Postoperative Pain......Page 1231
Procedure-Related Pain......Page 1232
Chemotherapy-Induced Nausea and Vomiting......Page 1233
Acute and Delayed Chemotherapy-Induced Nausea and Vomiting......Page 1234
Assessment......Page 1235
Principles of Pharmacologic Therapy......Page 1236
5-Hydroxytryptamine-3 Receptor Antagonists......Page 1237
Metoclopramide......Page 1238
Delayed Vomiting......Page 1239
Radiation-Induced Nausea and Vomiting......Page 1240
Nonpharmacologic Interventions......Page 1241
Constipation......Page 1242
Bowel Obstruction......Page 1243
DYSPNEA......Page 1244
Diagnosis and Assessment......Page 1245
Escalating Dyspnea......Page 1246
Impact......Page 1247
Associated Factors......Page 1248
Sleep......Page 1249
Stimulants......Page 1250
Pharmacologic Treatment......Page 1251
Depression......Page 1252
REFERENCES......Page 1253
Childhood Cancer Survivorship......Page 1268
Identifying Risk Factors for Late Effects......Page 1269
General Principles of Late Effects......Page 1271
Secondary Solid Tumors......Page 1272
Breast Cancer......Page 1274
Thyroid Cancer......Page 1275
Skin Cancer......Page 1276
Hematologic Malignancies......Page 1277
Cardiomyopathy......Page 1278
Coronary Artery Disease......Page 1279
Pulmonary System......Page 1280
Bone Disorders......Page 1281
Short Stature......Page 1282
Neurologic Disorders......Page 1283
Females......Page 1284
Pregnancy......Page 1285
Genitourinary System......Page 1286
Psychosocial Function......Page 1287
Comprehensive Clinical Evaluation......Page 1288
Medical History and Physical Examination......Page 1289
SPECIAL CONSIDERATIONS FOR THE HEMATOPOIETIC STEM CELL TRANSPLANT SURVIVOR......Page 1292
FUTURE DIRECTIONS......Page 1293
REFERENCES......Page 1294
Psychosocial Care of Children and Families......Page 1304
Conceptual Models Guiding the Psychosocial Care of Children and Families......Page 1305
Professional Roles and a Team Approach to Psychosocial Care......Page 1306
Parents’ Reactions to Children’s Illness......Page 1307
Children’s Reactions to Illness......Page 1309
Presenting Diagnoses and Plans for Treatment: The Day One Talk......Page 1310
Psychosocial Assessment of Patients and Families......Page 1312
Education and Information About Treatment......Page 1314
Support for Parents and Families During Treatment......Page 1315
Coping with Treatment and Side Effects......Page 1316
Home Care......Page 1317
Discipline......Page 1318
School......Page 1319
Peer Relationships......Page 1320
Depression and Anxiety......Page 1321
Adolescent Patients......Page 1322
REFERENCES......Page 1323
Ethical Considerations in Pediatric Oncology Clinical Trials......Page 1332
HISTORICAL PERSPECTIVE......Page 1333
What is “Consent” in Pediatrics?......Page 1334
Assent in Childhood Cancer Trials......Page 1336
Phase I and II Trials in Pediatric Oncology......Page 1339
CANCER TRIALS USING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION......Page 1340
MODELS AND TOOLS FOR ETHICAL DECISION MAKING......Page 1342
CHALLENGES OF TECHNOLOGY, GLOBALIZATION, AND ECONOMIC DISPARITY......Page 1345
CONCLUSION......Page 1346
REFERENCES......Page 1347
A......Page 1350
B......Page 1353
C......Page 1354
D......Page 1358
E......Page 1359
F......Page 1360
G......Page 1361
H......Page 1362
I......Page 1364
J......Page 1365
L......Page 1366
M......Page 1367
N......Page 1370
O......Page 1371
P......Page 1373
R......Page 1375
S......Page 1377
T......Page 1378
V......Page 1380
Z......Page 1381