Cancer: principles & practice of oncology
Gespeichert in:
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| Format: | Elektronisch E-Book |
| Sprache: | English |
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Philadelphia [u.a.]
Lippincott Williams & Wilkins
2005
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| Ausgabe: | 7. ed. |
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Datensatz im Suchindex
| _version_ | 1804135226651181056 |
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| adam_text | CONTENTS
PART M
MOLECULAR BIOLOGY OF CANCER
1
Molecular Methods In Oncology section 1 Amplification Techniques 3
PAUL M. LIZARDI
Improved Analysis of Mutations in Oncogenes and Tumor
Suppressor Genes 3
Highly Parallelized Single Nucleotide Polymorphism Assays Can Also Be
Used for Somatic Genotyping 4
Increasing the Accuracy of Sequence Information Derived from Polymerase
Chain Reaction Amplification 5
Multiplex Real Time Polymerase Chain Reaction Amplification for Detection
of Minimal Residual Disease or Viral Load 5
Mutation Detection Using In Situ Hybridization Methods Coupled with
DNA Amplification 5
High Throughput Methods for Measuring Gene
Dosage Alterations 6
Whole Genome Amplification of Microdissected Tissue 6
Amplification of Genomic Representations for Analysis of Gene
Gain/Loss 6
Tumor Classification Using Real Time Polymerase Chain Reaction to
Measure Messenger RNA Levels 6
XXX Contents
Biomarker Detection Using DNA Amplified Immunoassays 7
Amplification Based Approaches for DNA Methylation Analysis
in Cancer 7
suction 2 RNA Interference 8
RICHARD A. MORGAN
Biochemistry and Function 8
RNA Interference in Mammals 10
Cancer Applications 11
section 3 cDNA Arrays 13
KEVIN M. BROWN
INGRID A. HEDENFALK
JEFFREY M. TRENT
DNA Microarrays and the Molecular Profiling of
Human Cancers 13
Microarray Technology 13
Pediatric Acute Lymphoblastic Leukemia 15
Diffuse Large B Cell Lymphoma 18
Breast Cancer 19
Microarrays, Tumor Aggressiveness, and Metastasis 21
Are DNA Microarrays Ready for Routine Clinical Management of
Patients with Cancer? 22
Concluding Remarks 24
section 4 Tissue Arrays 26
MARISA DOLLED FILHART
DAVID L. RIMM
Tissue Microarray Construction 26
Tissue Microarray Visualization 28
Tissue Microarray Analysis 29
Tissue Microarray Applications 32
section 5 Cytogenetics 34
MAZIN B. QUMSIYEH
YESIM YILMAZ
Chromosome Structure and Function 34
Cytogenetic Methods 36
Chromosome Abnormalities in Cancer 38
Data Mining in Cancer Cytogenetics 42
sectio 6 Bioinformatics 43
KENNETH H. BUETOW
Flavors of Bioinformatics 44
Biomedical Informatics 44
Electronic Information Provisioning 44
In Silico Biomedical Applications 46
The Future 50
Conti nls vwi
2
Genomics and Proteomics 51
KATHERINE R. CALVO
EMANUEL F. PETRICOIN III
LANCE A. LIOTTA
Understanding Cancer at the Molecular Level: An Evolving Frontier 51
Genetic Mechanisms of Cancer Progression 51
Postgenome Challenge for Molecular Medicine 57
Tissue Microdissection Technology Brings Molecular Analysis to the Tissue Level 58
Complementary DNA Microarrays As a Tool to Analyze Gene Expression Patterns in Human Cancer 59
Beyond Functional Genomics to Cancer Proteomics 63
Molecular Diagnostics and Individualized Cancer Therapy 63
Serum Proteomics 67
3
Molecular Targets in Oncology. 73
section 1 Signal Transduction Systems 73
CHRISTOPHER L. CARPENTER
LEWIS C. CANTLEY
Sensory Machinery: Ligands and Receptors 73
Propagation of Signals to the Cell Interior 76
Efficiency and Specificity: Formation of Multiprotein Signaling Complexes SO
Regulation of Protein Levels: Transcription, Translation, and Proteolysis SI
section 2 Cell Cycle 83
STEVEN I. REED
Cell Cycle Engine 83
Regulation of the Cell Cycle 87
Cell Cycle and Cancer 90
Cell Cycle As a Target for Therapy 93
Conclusion 94
section 3 Apoptosis 95
SANDRA S. ZINKEL
STANLEY J. KORSMEYER
Genetics of Cell Death 95
Bcl 2 Family 95
Critical Role of Apoptosis in Tissue Homeostasis 98
Caspases 99
Death Receptors 99
Apoptosome 99
Inhibitors of Apoptosis 101
Role of Intracellular Organelles: Mitochondria and Endoplasmic Reticulum 101
Cell Proliferation and Apoptosis 101
Possibilities for Therapeutic Intervention 102
Conclusion 102
YY.vii Con/mis
sKcnos 4 Telomerase 105
KWOK KIN WONG
RONALD A. DEPINHO
Telomeres 105
Telomerase Structure, Regulation, and Function 106
Crisis, Telomerase Reactivation, and Alternative Lengthening of Telomeres 106
Telomere Maintenance and Cancer 107
Aging and Cancer 707
Telomere Dynamics, Inflammatory Diseases, and Cancer 108
Telomere Status as a Biomarker for Cancer 109
Telomerase and Telomere Maintenance As Therapeutic Targets 109
Rational Clinical Trial Designs of Telomere and Telomerase
Based Therapeutics 111
4
Invasion and Metastases 113
WILLIAM G. STETLER STEVENSON
Tumor Progression and Genetic Instability 113
Origins of Metastatic Tumor Cells 114
Microarray Analysis of Tumor Progression and Metastasis 115
Tumorigenesis and Metastasis Are Under Separate Genetic Control: Tumor Suppressor Genes 116
Metastatic Cascade 117
Tumor Microenvironment: Determinant of Metastatic Potential and Site of Metastasis 118
Tumor Cell Motility 119
Tumor Invasion of the Basement Membrane 119
Initiation of Cell Migration 119
Cell Cell Adhesion: Metastasis Suppressor 120
Cell Matrix Interactions and Tumor Cell Migration 121
Role of CD44 in Tumor Invasion and Metastasis 121
Role of Integrins in Tumor Progression 722
Cell Migration 724
Proteases in Tumor Cell Invasion 725
Conclusion 726
5
Angiogenesis 129
ISAIAH J. FIDLER
ROBERT R. LANGLEY
ROBERT S. KERBEL
LEE M. ELLIS
Neoplastic Angiogenesis 129
Phenotypic Diversity of Organ Specific Endothelial Cells 131
Tumor Vasculature 752
Host Mediated Angiogenesis 752
Overview of Antiangiogenic and Antivascular Therapies 133
Antivascular Therapy for Bone Metastasis 134
Clinical Studies of Imatinib 755
Discrepancy between Results of Preclinical and Clinical Trials 755
Contents V iii
Basic Principles for Design of Clinical Trials of Antiangiogenic Agents / 3 5
Conclusion 136
6
Cancer Immunology 139
NICHOLAS P. RESTIFO
JOHN R. WUNDERLICH
Antitumor T Cells 140
Biologic Sources of Tumor Associated Antigens 140
Presentation of Tumor Antigens to T Cells 141
Role of Antigen Presenting Cells in Activating Antitumor T Cells 146
T Cell Recognition of Tumor Antigens 148
Maturation of Antitumor T Cells 149
Activation of Mature Antitumor T Cells 750
Activation States of Antitumor T Cells 154
* Functions of Mature Antitumor T Cells 155
Conclusion 157
part £
PRINCIPLES OF ONCOLOGY
7
Etiology of Cancer: Viruses 165
section 1 RNA Viruses 165
GARY L. BUCHSCHACHER JR
FLOSSIE WONG STAAL
Retroviruses: Background, Replication Cycle, and Molecular Genetics 165
Mechanisms of Retroviral Oncogenesis 166
Human T Lymphotropic Virus Type 1 168
Human T Lymphotropic Virus Type 2 169
Human Immunodeficiency Virus 169
Hepatitis C Virus 171
section 2 DNA Viruses 173
PETER M. HOWLEY
DON GANEM
ELLIOT KIEFF
Hepadnaviruses and Hepatocellular Carcinoma / 74
Papillomaviruses and Human Cancer 175
Epstein Barr Virus 180
Kaposi s Sarcoma Associated Herpesvirus 181
Simian Vacuolating Virus 40 and the Human Polyomaviruses 183
xxxiv Contents
8
Etiology of Cancer: Chemical Factors 185
STUART H. YUSPA
PETER G. SHIELDS
Nature of Chemical Carcinogens: Chemistry and Metabolism 185
Animal Model Systems and Chemical Carcinogenesis 186
DNA Repair Protects the Host from Chemical Carcinogens 187
Genetic Susceptibility to Chemical Carcinogenesis 187
Determination of Chemical Carcinogens for Humans and Population
Based Risk Assessment 187
Chemical Carcinogenesis and Cancer Risk 757
Tumor Suppressor Genes in Human Cancer 189
Tobacco Smoking and Cancer Risk 190
9
Etiology of Cancer: Tobacco Use 193
GRAHAM A. COLDITZ
LAURIE B. FISHER
Effects of Tobacco Use and Cessation on Cancer Risk 193
Effect of Tobacco Use on Cardiovascular Disease 196
Cigars, Pipes, and Smokeless Tobacco 196
Secondhand Tobacco Smoke 797
National Trends in Smoking Prevalence 797
Disparities in Active Tobacco Use and Cessation 797
Cigarette Product Modification—Harm Reduction 7 98
Tobacco and Nicotine Addiction 795
Role of the Clinician 7 98
Strategies for Tobacco Control 795
Conclusion 7 98
10
Etiology of Cancer: Physical Factors 201
ROBERT L. ULLRICH
Interactions of Radiation with Cells and Tissues 202
Ultraviolet Light 211
Asbestos 213
11
Epidemiology of Cancer 217
skctiox 1 Epidemiologic Methods 217
XIAOMEI MA
MARGARET A. TUCKER
Descriptive Studies 218
Contents
Analytic Studies 219
Interpretation of Epidemiologic Findings 222
3 Special Topic: Molecular and Genetic Epidemiology 22
section 2 Cancer Statistics 226
AHMEDIN JEMAL
ELIZABETH M. WARD
MICHAEL J. THUN
Measures of the Cancer Burden 226
Data Sources and Age Standardization 230
Temporal Trends 231
Demographic and Geographic Patterns 234
Issues in the Interpretation and Understanding of
Temporal Trends 238
Conclusion 240
5 12
Principles of Surgical Oncology 243
section 1 General Issues 243
STEVEN A. ROSENBERG
Historical Perspective 243
Anesthesia for Oncologic Surgery 244
Determination of Operative Risk 246
Roles for Surgery 249
Surgical Oncologist 251
section 2 Laparoscopic Surgery 253
ALBERT S. KO
ALAN T. LEFOR
Physiology of Laparoscopy 253
Port Site Metastases 255
Laparoscopy in the Diagnosis of Malignancy 257
Laparoscopy in the Staging of Malignancy 258
Laparoscopy in the Treatment of Malignancy 263
Laparoscopy in the Palliation of Malignancy 265
Conclusion 265
13
Principles of Radiation Oncology 267
PHILIP P. CONNELL
MARY K. MARTEL
SAMUEL HELLMAN
Biologic Aspects of Radiation Oncology 267
Physical Aspects of Radiation Oncology 276
Clinical Aspects of Radiation Oncology 285
VVWi Contents
14
Principles of Medical Oncology. 29£
EDWARD CHU
VINCENT T. DEVITA, JR.
Historical Perspective 295
Clinical Application of Chemotherapy 296
Clinical End Points in Evaluating Response to Chemotherapy 297
Cancer Cell Kinetics and Response to Chemotherapy 298
Principles Governing the Use of Chemotherapy 298
Concept of Dose Intensity 300
Apoptosis, Cell Cycle Control, and Resistance to Chemotherapy 301
15
Pharmacology of Cancer Chemotherapy 307
section 1 Drug Development 307
EDWARD CHU
Drug Discovery 307
Combinatorial Chemistry 309
Drug Screening 311
Molecularly Targeted Screening 312
Preclinical Pharmacology 313
Formulation Studies 314
Preclinical Toxicology 315
Clinical Development 315
Conclusion 316
section 2 Pharmacokinetics 317
CHRIS H. TAKIMOTO
Introduction 317
Pharmacokinetic Concepts 319
Pharmacodynamic Concepts 323
Special Topics in Pharmacokinetics and Pharmacodynamics 324
Pharmacokinetics and Pharmacodynamics in Oncology Drug Development 325
Conclusion 326
section 3 Pharmacogenomics 327
HOWARD L. MCLEOD
BOON CHER GOH
Pharmacogenomics of Chemotherapy Drug Toxicity 327
Pharmacogenomics of Tumor Response 330
Conclusion 331
section 4 Alkylating Agents 332
O. MICHAEL COLVIN
HENRY S. FRIEDMAN
History of the Alkylating Agents 332
Contents xxxvii
Chemistry and Cytotoxicity of Alkylating Agents 332
Classes of Alkylating Agents and Their Properties 332
Mechanisms of Toxicity and Drug Resistance 338
Common Toxicities of Alkylating Agents 340
section 5 Cisplatin and Its Analogues 344
STEVEN W. JOHNSON
PETER J.O DWYER
History 344
Platinum Chemistry 345
Novel Platinum Complexes 345
Mechanism of Action 347
Mechanisms of Resistance 349
Clinical Pharmacology 352
Formulation and Administration 354
r Toxicity 354
section 6 Antimetabolites 358
SHIVAANIKUMMAR
VANITA NORONHA
EDWARD CHU
Methotrexate 358
New Antifolates 361
section 7 Topoisomerase Interactive Agents 375
CHRIS H. TAKIMOTO
Mammalian Topoisomerases 375
Mechanism of Action of Topoisomerase Interactive Agents 377
Camptothecins 377
Epipodophyllotoxins 381
Anthracyclines and Related Compounds 384
Other Topoisomerase Interactive Agents 388
Secondary Malignancies and Topoisomerase Targeting Therapies 389
section 8 Antimicrotubule Agents 390
ERIC K. ROWINSKY
ANTHONY W. TOLCHER
Microtubules 390
Vinca Alkaloids 392
Taxanes 398
Estramustine Phosphate 407
Novel Compounds Targeting Microtubules 410
Novel Compounds Targeting Mitotic Motor Proteins 411
section 9 Miscellaneous Chemotherapeutic Agents 416
MEHMET SITKI COPUR
MICHAL G. ROSE
EDWARD CHU
L Asparaginase 416
W iii Contents
Bleomycin 427
Imatinib Mesylate 417
Gefitinib 418
Bortezomib 420
16
Pharmacology of Cancer Biotherapeutics 423
suction 1 Interferons 423
VERNON K. SONDAK
BRUCE G. REDMAN
Interferon Induction 423
Biologic Effects of Interferons 424
Clinical Toxicity of Interferon Administration 426
Potential Drug Interactions 427
Oncologic Applications of Interferons 427
Conclusion 429
section 2 Interleukin 2 431
JAMES W. MIER
MICHAEL B. ATKINS
Isolation, Characterization, and Cloning of Interleukin 2 431
Interleukin 2 Receptor 431
Interleukin 2 Activated Signaling Pathways 431
In Vitro Effects of Interleukin 2 432
Preclinical Studies with Interleukin 2 in Tumor Bearing Mice 432
Clinical Applications of Interleukin 2 432
Conclusion 437
section 3 Histone Deacetylase Inhibitors: New Targeted Anticancer Drugs 439
PAUL A. MARKS
VICTORIA M. RICHON
THOMAS A. MILLER
WM. KEVIN KELLY
Chromatin Structure 439
Histone Deacetylases and Histone Acetyl Transferases 439
Histone Acetyltransf erases and Histone Deacetylase Inhibitors and Human Cancers 439
Histone Deacetylase Inhibitors 441
Activity of Histone Deacetylase Inhibitors 441
Clinical Trials with Histone Deacetylase Inhibitors 443
Conclusion and Perspectives 444
section 4 Monoclonal Antibodies 445
JONATHAN D. CHENG
GREGORY PAUL ADAMS
MATTHEW K. ROBINSON
LOUIS M. WEINER
Immunoglobulin Structure 446
Contents
Factors Regulating Antibody Based Tumor Targeting 447
Unconjugated Antibodies 448
Immunoconjugates 451
Pretargeted Antibody Conjugates 453
Unconjugated Antibodies with Clinical Activity in
Solid Tumors 453
Conclusion 454
17
Pharmacology of Endocrine Manipulation 457
MATTHEW P. GOETZ
CHARLES ERLICHMAN
CHARLES L. LOPRINZI
Selective Estrogen Receptor Modulators 457
Medroxyprogesterone and Megestrol 461
Aromatase Inhibitors 462
Gonadotropin Releasing Hormone Analogues 464
Antiandrogens 464
Fluoxymesterone 465
Diethylstilbestrol and Estradiol (Estrace) 465
Octreotide 466
18
Design and Analysis of Clinical Trials 471
RICHARD M. SIMON
Phase I Clinical Trials 471
Phase II Clinical Trials 473
Design of Phase III Clinical Trials 478
Analysis of Phase III Clinical Trials 483
PARTlS
PRACTICE OF ONCOLOGY
19
Cancer Prevention: Preventing Tobacco Related Cancers 493
HOWARD K. KOH
ALAN C. GELLER
Tobacco and Nicotine Addiction 493
Health Effects 493
Smoking Rates and Trends 494
Adults 494
Children, Adolescents, and College Students 495
l Contents
Cigarette Product Modification 495
Spit Tobacco 496
Cigars 496
Environmental Tobacco Smoke 496
Tobacco Industry Advertising Strategies 497
Strategies for Tobacco Control 498
Individual Approaches 498
Clinician s Role 498
Nicotine Replacement Therapy 499
Special Populations 500
National Action Plan for Tobacco Cessation 500
Tobacco Restrictions at the Policy Level 500
Tobacco Taxes that Fund Dedicated, Comprehensive Statewide Tobacco Control Programs 500
Mass Media and Counter Advertising 501
Tobacco Litigation, Tobacco Settlement, and International Treaties 502
Proposed U.S. Food and Drug Administration Regulations 502
Conclusion 503
20
Cancer Prevention: Diet and Chemopreventive Agents 507
skction 1 Dietary Fat 507
WALTER C. WILLETT
Fat and Breast Cancer 508
Fat and Colon Cancer 509
Fat and Prostate Cancer 510
Fat and Other Cancers 511
Conclusion 511
sectios 2 Dietary Fiber 514
KARIN B. MICHELS
Diet and Cancer Etiology 514
Properties of Dietary Fiber 514
Observational Studies and Clinical Trials 514
Types of Dietary Fiber 515
Calculation of Fiber Intake 515
Dietary Fiber and Colorectal Cancer 515
Fiber Intake and Colorectal Adenomas 516
Fiber Intake and Breast Cancer 516
Dietary Fiber and Stomach Cancer 516
Timing of Diet 517
Conclusion 517
si;cti ) 3 Fruit and Vegetable Consumption 518
KARIN B. MICHELS
Fruits and Vegetables 518
Diet Assessment Instruments 518
Confounding 518
Fruit and Vegetable Consumption and Colorectal Cancer 518
C.onlnils li
Fruit and Vegetable Consumption and Stomach Cancer 518
Fruit and Vegetable Consumption and Breast Cancer 579
Fruit and Vegetable Consumption and Lung Cancer 579
Micronutrient Components of Fruits and Vegetables and Cancer 579
Conclusion 520
section 4 Retinoids, Carotenoids, and Micronutricnts 521
SUSAN T. MAYNE
SCOTT M. LIPPMAN
Historical Perspective 527
Retinoid Biology and Pharmacology 522
Carotenoid Biology and Actions 522
Clinical Trials 523
Translational and Intermediate End Point Studies in Retinoid Chemoprevention 532
Other Retinoids and Carotenoids 533
Conclusion 533
section 5 Dietary Carcinogens 536
PETER GREENWALD
Naturally Occurring Dietary Carcinogens 536
Products of Food Preparation and Processing 538
Synthetic Carcinogens in the Diet 540
Future Research Needs 540
section G Cyclooxygenasc Inhibitors 541
MICHAEL J. THUN
S. JANE HENLEY
Pharmacology of Nonsteroidal Antiinflammatory Drugs 547
Toxicity of Nonsteroidal Antiinflammatory Drugs 542
History of the Inflammation Hypothesis 542
Nonsteroidal Antiinflammatory Drugs in Relation to Other Cancers 543
Mechanisms of Cancer Inhibition 544
Molecular Target(s) 546
Ongoing Randomized Clinical Trials 546
Implications for Research and Clinical Practice 546
Conclusion 548
section 7 Physical Activity and Body Weight 549
GRAHAM A. COLDITZ
KATHLEEN YAUS WOLIN
Physical Activity 549
Obesity 552
Conclusion 553
21
Cancer Prevention: Role of Surgery in Cancer Prevention 555
RICHARD M. SHERRY
Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid Carcinoma 555
vlii Contents
Barrett s Esophagus and Esophageal Cancer 556
Hereditary Diffuse Gastric Cancer 558
Colorectal Cancer 558
Breast Cancer 561
Ovarian Cancer 563
Testicular Cancer and Cryptorchidism 564
22
Cancer Screening 567
BARBARA K. RIMER
JOELLEN M. SCHILDKRAUT
ROBERT A. HIATT
What Is Cancer Screening? 567
Evaluation of a Screening Test 568
Breast Cancer Screening 569
Cervical Cancer Screening 572
Colorectal Cancer Screening 573
Skin Cancer Screening 574
Prostate Cancer Screening 574
Lung Cancer Screening 576
Adherence to Cancer Screening 577
Future of Screening 577
23
Advanced Molecular Diagnostics 581
JOSE C. COSTA
PAUL M. LIZARDI
Present Impact of Novel Technologies on Clinical Practice 582
Charting the Future 584
Conclusion 586
24
Advanced Imaging Methods 589
SEcrios 1 Functional and Metabolic Imaging 589
HEDVIG HRICAK
OGUZ AKIN
MICHELLE S. BRADBURY
LAURA LIBERMAN
LAWRENCE H. SCHWARTZ
STEVEN M. LARSON
Imaging Modalities 589
Therapeutic Response Assessment 594
Brain and Head/Neck Cancers 595
Lung Cancer 597
Lymphoma 600
Breast Cancer 601
Hepatobiliary Cancer 604
Colorectal Cancer 605
Contents xliii
Gynecologic Cancer 607
Endometrial Cancer 607
Cervical Cancer 608
Ovarian Cancer 609
Prostate Cancer 610
Molecular Imaging in Oncology 611
section 2 Interventional Radiology 617
ANNE M. COVEY
KAREN T. BROWN
Percutaneous Biopsy 617
Central Venous Access 619
Gastrointestinal Procedures 629
Genitourinary Procedures 620
Biliary Procedures 623
Chest Interventions 626
Inferior Vena Cava Filters 629
Ascites 630
Abscess Drainage 631
Embolotherapy for Hepatic Neoplasms 631
Tumor Ablation 632
Emerging Therapies and Future Directions 634
25
Cancer Diagnosis: Endoscopy 637
section 1 Gastrointestinal Endoscopy 637
IRVING WAXMAN
Upper Endoscopy 637
Colonoscopy 640
Endoscopic Ultrasonography 641
Small Bowel Endoscopy and Capsule Endoscopy 641
Endoscopic Retrograde Cholangiopancreatography 642
section 2 Respiratory Tract 643
DAO M. NGUYEN
RONALD M. SUMMERS
STEVEN E. FINKELSTEIN
Bronchoscopy 643
Virtual Bronchoscopy 645
Cervical Mediastinoscopy and Anterior Mediastinotomy 647
Video Assisted Thoracoscopy 648
26
Cancer of the Head and Neck 653
section 1 Molecular Biology of Head and Neck Tumors 653
DAVID SIDRANSKY
Genetic Susceptibility 653
xliv Contents
Cytogenetic Alterations 653
Protooncogenes 654
Suppressive Growth Regulation 655
Tumor Suppressor Genes 655
Field Cancerization 657
Molecular Epidemiology 658
Human Papillomavirus 658
Diagnostics 658
section 2 Treatment of Head and Neck Cancers 662
WILLIAM M. MENDENHALL
CHARLES E. RIGGS, JR.
NICHOLAS J. CASSISI
Epidemiology of Head and Neck Cancer 662
Anatomy 662
Pathology 662
Natural History and Patterns of Spread of Squamous
Cell Carcinoma 663
Diagnostic Evaluation 665
Staging 665
General Principles for Selection of Treatment 665
Management 666
section 3 Rehabilitation after Treatment for Head and Neck Cancer 732
MICHAEL A. CRARY
GISELLE D. CARNABY (MANN)
General Functional Consequences of Treatment for Head and
Neck Cancer 732
Tracheostomy Issues 734
Radiation Therapy Impact on Speech, Voice, and Swallowing
Functions 735
Evaluation of Speech, Voice, and Swallowing after Head and Neck
Cancer Treatment 736
Rehabilitation of Posttreatment Functional Limitations 738
Conclusion 742
27
Cancer of the Lung 745
section 1 Molecular Biology of Lung Cancer 745
YOSHITAKA SEKIDO
KWUN M. FONG
JOHN D. MINNA
Genetic and Epigenetic Alterations in Lung Cancers 745
Protooncogenes and Growth Stimulation 746
Tumor Suppressor Genes and Growth Suppression 748
Other Biologic Abnormalities for Lung Cancer Development 749
Molecular Tools in the Lung Cancer Clinic 751
C.onli nls vlv
section 2 Non Small Cell Lung Cancer 753
DAVID S. SCHRUMP
NASSER K. ALTORKI
CLAUDIA L. HENSCHKE
DARRYL CARTER
ANDREW T. TURRISI
MARTIN E. GUTIERREZ
Incidence 753
Etiology 753
Pathology 757
Modes of Metastasis 761
Clinical Manifestations 762
Staging and Diagnosis 763
Methods to Establish Tissue Diagnosis 766
Lung Cancer Screening 768
Chemoprevention 770
Overview of Invasive Lung Cancer Management: Treatment Modalities 770
Specifics of Lung Cancer Management 777
section 3 Small Cell Lung Cancer 810
JOHN R. MURREN
ANDREW T. TURRISI
HARVEY I. PASS
Epidemiology and Etiology 810
Pathology 810
Clinical Presentation 811
Staging Evaluation and Prognostic Factors 812
Treatment 815
Combination Chemotherapy 816
Duration of Chemotherapy 818
Approach to Patients with Limited Disease 819
Role of Radiotherapy in Limited Disease 820
Role of Surgery in Limited Disease 823
Approach to Patients with Extensive Disease 826
Strategies to Optimize Chemotherapy Response 827
Hematopoietic Growth Factors 830
Management of Small Cell Lung Cancer in the Elderly and Infirm 832
Biologic Response Modifiers and Other Treatments 833
Treatment at Relapse 834
Treatment Outcome and Long Term Survival 835
Extrapulmonary Small Cell Carcinoma 836
28
Neoplasms of the Mediastinum 845
ROBERT B. CAMERON
PATRICK J. LOEHRER, SR.
CHARLES R. THOMAS, JR.
Anatomy 845
Incidence and Pathology 845
Diagnostic Considerations 846
hi Contents
Thymic Neoplasms 848
Germ Cell Tumors 852
Mesenchymal Tumors 855
Neurogenic Tumors 855
Primary Cardiac Malignancies 858
29
Cancers of the Gastrointestinal Tract 861
sm:tio 1 Cancer of the Esophagus 861
MITCHELL C. POSNER
ARLENE A. FORASTIERE
BRUCE D. MINSKY
Epidemiology 861
Etiologic Factors and Predisposing Conditions 862
Applied Anatomy and Histology 865
Molecular Biology 867
Natural History and Patterns of Failure 869
Clinical Presentation 869
Diagnostic Studies and Pretreatment Staging 870
Pathologic Staging 871
Treatment 872
Stage Directed Treatment Recommendations 901
sh:cTio 2 Cancer of the Stomach 909
PETER W. T. PISTERS
DAVID P. KELSEN
STEVEN M. POWELL
JOEL E. TEPPER
Epidemiology and Etiology 909
Molecular Biology 912
Pathology and Tumor Biology 914
Clinical Presentation and Pretreatment Evaluation 915
Staging, Classification, and Prognosis 917
Treatment of Localized Disease 921
Treatment of Advanced Disease (Stage IV) 934
shctk) 3 Cancer of the Pancreas 945
CHARLES J. YEO
THERESA PLUTH YEO
RALPH H. HRUBAN
SCOTT E. KERN
CHRISTINE A. IACOBUZIO DONOHUE
ANIRBAN MAITRA
MICHAEL GOGGINS
MARCIA I. CANTO
WELLS MESSERSMITH
ROSS A. ABRAMS
DANIEL A. LAHERU
MANUEL HIDALGO
ELIZABETH M. JAFFEE
Epidemiology and Risk Factors 945
Contents xlvii
Pathology 947
Molecular Genetics 950
Gene Expression Profiling and Beyond 952
Screening and Early Detection 953
Clinicopathologic Staging 955
Clinical Presentation and Evaluation 957
Treatment of Potentially Resectable Disease 960
Treatment of Locally Advanced Disease 969
Treatment of Metastatic and Recurrent Disease 973
Immunotherapy 982
section 4 Cancer of the Liver 986
DAVID L. BARTLETT
BRIAN I. CARR
J. WALLIS MARSH
Epidemiology 987
Etiologic Factors 988
Pathology 992
Clinical Features 991
Staging 993
Clinical Evaluation 993
Screening of High Risk Populations 995
Clinical Management 996
Treatment of Other Primary Liver Tumors 2003
Summary: Practical Guide to the Management of Patients
with Hepatocellular Carcinoma 2004
section 5 Cancer of the Biliary Tree 1009
DAVID L. BARTLETT
RAMESH K. RAMANATHAN
MELVIN DEUTSCH
Cholangiocarcinomas 2009
Tumors of the Gallbladder 2022
New Advances for Treatment of Biliary Tract Cancers 2032
section 6 Cancer of the Small Intestine 1035
HERBERT J. ZEH III
Incidence 2036
Pathogenetic Mechanisms in Small Intestinal Carcinogenesis 2036
Genetic and Environmental Factors That Predispose to Malignancy
Arising in the Small Intestine 2037
Presentation and Diagnosis of Cancers Arising in the Small Intestine 1038
Adenocarcinoma Arising in the Small Intestine 2040
Carcinoid Tumors Arising in the Small Intestine 2042
Lymphoma Arising in the Small Intestine 2044
Mesenchymal Tumors Arising in the Small Intestine 2046
section 7 Gastrointestinal Stromal Tumors 1050
GEORGE D. DEMETRI
Histopathologic Features and Histogenesis 2050
Ylviii Contents
Clinical Considerations 1052
Treatment Options and Management Decisions in the Era of Molecularly Targeted Therapies f
Gastrointestinal Stromal Tumor 2054
Special Considerations in Gastrointestinal Stromal Tumor 1058
New Challenges and Alternative Approaches 1059
section 8 Cancer of the Colon 1061
STEVEN K. LIBUTTI
LEONARD B. SALTZ
ANIL K. RUSTGI
JOEL E. TEPPER
Epidemiology 1061
Etiology: Genetic and Environmental Risk Factors 1062
Biology of Colorectal Cancer: Clinical and Molecular
Genetic Risk Factors 1063
Anatomy of the Colon 1065
Diagnosis 2067
Screening 1068
Staging and Prognosis 1068
Approaches to Surgical Resection of Colon Cancer 1076
Polyps and Stage I Colon Cancer 1080
Stage II and Stage HI Colon Cancer 1080
Surgical Management of Stage IV Disease 2089
Management of Unresectable Metastatic Disease 1089
Management of Synchronous Primary and Metastatic Disease 2202
Unusual Colorectal Tumors 2 2 02
section 9 Cancer of the Rectum 1110
STEVEN K. LIBUTTI
JOEL E. TEPPER
LEONARD B. SALTZ
ANIL K. RUSTGI
Anatomy 2220
Staging 2222
Surgery 2223
Stage I 2223
Combined Modality Therapy (Stages II and III) 2226
Concurrent Chemotherapy 2229
Management of Unresectable Primary and Locally Advanced
Disease (T4) 2220
Radiation Therapy Technique 2222
Radiation Fields 2222
section 10 Cancer of the Anal Region 1125
BERNARD J. CUMMINGS
JAFFERA.AJANI
CAROL J. SWALLOW
Anatomy 2225
Pathology 2226
Epidemiology 2226
Risk Factors and Etiology 2226
Contents
Natural History 2227
or Staging 1128
Prognostic Factors 7229
Anal Canal Squamous Cancers 1129
Adenocarcinomas 1135
Small Cell Cancers 1135
Perianal Cancers 1135
Special Considerations: Patients with Human Immunodeficiency Virus Infection/
Acquired Immunodeficiency Syndrome 1136
30
Cancers of the Genitourinary System 1139
section 1 Cancer of the Kidney 1139
W. MARSTON LINEHAN
SUSAN E. BATES
JAMES C. YANG
Histologic Types of Renal Carcinoma 1139
Localized Renal Carcinoma 1149
Metastatic Renal Carcinoma 2252
section 2 Cancer of the Bladder, Ureter, and Renal Pelvis 1168
WILLIAM U. SHIPLEY
DONALD S. KAUFMAN
W. SCOTT MCDOUGAL
DOUGLAS M. DAHL
M. DROR MICHAELSON
ANTHONY L. ZIETMAN
Epidemiology 2265
Screening and Early Detection 1169
Pathology 2269
Molecular Tumor Markers 1170
Cancer of the Bladder 2 2 72
Cancers of the Ureter and Renal Pelvis 2285
section 3 Cancer of the Prostate 1192
HOWARD I. SCHER
STEVEN A. LEIBEL
ZVI FUKS
CARLOS CORDON CARDO
PETER T. SCARDINO
States and State Transitions 2292
Biologic Characterization and Pathology 2 295
Initial Urologic Evaluation: No Cancer Diagnosis 2203
Localized Disease 2209
Radiation Therapy 2222
Expectant Management 2230
Systemic Therapies 2232
Clinical Metastases: Castrate 2242
Conclusion 2250
section 4 Cancer of the Urethra and Penis 1260
SANJAY RAZDAN
LEONARD G. GOMELLA
Cancer of the Male Urethra 1260
Carcinoma of the Female Urethra 1261
Cancer of the Penis 1262
31
Cancer of the Testis 1269
GEORGE J. BOSL
DEAN F. BAJORIN
JOEL SHEINFELD
ROBERT J.MOTZER
R. S. K. CHAGANTI
Background: Incidence 1269
Epidemiology 1269
Initial Presentation and Management 1270
Histology 1270
Staging 1274
Management of Clinical Stage I Disease 1277
Management of Clinical Stage II Disease (Low Tumor Burden) 1281
Management of Stage II and Stage III Disease (High Tumor Burden) 1282
Management of Relapse after Chemotherapy and Refractory Disease 1286
Treatment Sequelae 1287
Midline Tumors of Uncertain Histogenesis 1289
Other Testicular Tumors 1289
32
Gynecologic Cancers 1295
section 1 Cancer of the Cervix, Vagina, and Vulva 1295
PATRICIA J. EIFEL
JONATHAN S. BEREK
MAURIE A. MARKMAN
Carcinoma of the Cervix 1295
Carcinoma of the Vagina 1320
Carcinoma of the Vulva 1326
section 2 Cancers of the Uterine Body 1341
THOMAS W. BURKE
ARNOJ. MUNDT
FRANCO M. MUGGIA
Endometrial Carcinoma 1341
Uterine Sarcomas 2354
section 3 Gestational Trophoblastic Diseases 1360
FRANCO M. MUGGIA
THOMAS W. BURKE
WILLIAM SMALL, JR
Epidemiology 1360
Pathology and Biology 7367
Clinical Diagnosis and Human Chorionic Gonadotropin 7367
Choriocarcinoma 7362
suction 4 Ovarian Cancer, Peritoneal Carcinoma, and Fallopian l ibe Carcinoma 1364
BETH Y. KARLAN
MAURIE A. MARKMAN
PATRICIA J. EIFEL
Ovarian Cancer 7364
Borderline Tumors 1388
Primary Peritoneal Carcinoma 7389
Germ Cell Tumors of the Ovary 7390
Sex Cord Stromal Tumors 7392
Fallopian Tube Cancer 1393
33
Cancer of the Breast 1399
section 1 Molecular Biology of Breast Cancer 1399
ROBERT B. DICKSON
RICHARD G. PESTELL
MARC E. LIPPMAN
Genetics 7399
Steroid and Growth Factor Pathways of Cellular Regulation 7402
Cell Cycle and Cell Death 7408
Process of Malignant Progression 7470
Implications of Molecular Biology for Tumor Prevention, Early Detection,
Prognosis, and Response to Therapy 7477
section 2 Malignant Tumors of the Breast 1415
WILLIAM C. WOOD
HYMAN B. MUSS
LAWRENCE J. SOLIN
OLUFUNMILAYO I. OLOPADE
Risk Factors for Breast Cancer 7475
Diagnosis and Biopsy 1418
Pathologic Classification of Tumor Types 7420
Staging of Breast Cancer 1421
Prognostic and Predictive Factors 7423
Advising the Woman at High Risk for Breast Cancer 7427
Ductal Carcinoma In Situ 1429
Lobular Carcinoma In Situ 1434
Paget s Disease 7434
Early Stage Breast Cancer 7435
Locally Advanced and Inflammatory Breast Cancer 7450
Metastatic Breast Cancer 7453
Breast Cancer and Pregnancy 7462
Bilateral Breast Cancer 7464
Male Breast Cancer 7465
Nonepithelial Neoplasms 7465
lii Contents
Lymphoma of the Breast 1466
Axillary Lymph Node Presentation 1466
Local and Regional Recurrence 1467
Breast Cancer in the Elderly 1469
section 3 Rehabilitation after Treatment for Cancer of the Breast 1478
JEANNE A. PETREK
JOSEPH J. DISA
Delayed versus Immediate Reconstruction 1478
Prosthetic Reconstruction 1478
Autologous Tissue Reconstruction 1479
Postmastectomy after Breast Irradiation 1481
Skin Sparing Mastectomy with Immediate Reconstruction 1481
Lymphedema 1483
34
Cancer of the Endocrine System 1489
section 1 Molecular Biology of Endocrine Tumors 1489
TERRY C. LAIRMORE
JEFFREY F. MOLEY
Multiple Endocrine Neoplasia Syndromes 1489
Molecular Pathogenesis of Sporadic Thyroid Neoplasms 1495
Genetic Abnormalities in Parathyroid Neoplasms 2497
Other Genetic Loci Implicated in Familial Hypercalcemic Syndromes 1498
Parathyroid Carcinoma 1499
Genetic Abnormalities in Adrenal Neoplasms 1499
Conclusion 1500
section 2 Thyroid Tumors 1502
TOBIAS CARLING
ROBERT UDELSMAN
Thyroid Tumor Classification and Staging Systems 1502
Epidemiology and Demographics 1503
Etiology and Risk Factors 1503
Evaluation of the Thyroid Nodule 1506
Well Differentiated Thyroid Carcinoma 1508
Treatment of Well and Intermediately Differentiated
Thyroid Carcinoma 1510
Poorly Differentiated Thyroid Carcinoma 1514
Medullary Thyroid Carcinoma 1515
Thyroid Lymphoma 1517
Metastatic Disease of the Thyroid 1518
Thyroid Carcinoma in Children 1518
section 3 Parathyroid Tumors 1521
DOUGLAS L. FRAKER
Primary Hyperparathyroidism 1521
Pathology 1521
Molecular Genetics 2522
Epidemiology 7522
Clinical Presentation 7524
Natural History 7524
Differential Diagnosis 7525
Treatment 7525
Outcome 7526
section 4 Adrenal Tumors 1528
JEFFREY A. NORTON
Pathology of the Adrenal Cortex 1528
Clinical Presentations of Adrenal Cortical
Neoplasms 7529
Treatment of Adrenal Cortical Neoplasms 7533
Pheochromocytoma 7535
section 5 Pancreatic Endocrine Tumors 1540
H. RICHARD ALEXANDER, JR
ROBERT T. JENSEN
Pathogenesis, Pathology, Tumor Biology 7547
Clinical Presentation and Diagnosis 7543
Imaging and Localization of Pancreatic
Endocrine Tumors 7547
Treatment of Resectable Disease 7548
Treatment of Metastatic Disease 7555
suction 6 Carcinoid Tumors and the Carcinoid Syndrome 1559
ROBERT T. JENSEN
GERARD M. DOHERTY
Pathology and Tumor Histology 7559
Molecular Pathogenesis 7562
Clinical Features 7562
Carcinoid Syndrome 1563
Treatment of the Carcinoid Tumor 7577
section 7 Multiple Endocrine Neoplasias 1575
GERARD M. DOHERTY
ROBERT T. JENSEN
Multiple Endocrine Neoplasia Type 1 7575
Familial Medullary Thyroid Carcinoma and Multiple Endocrine Neoplasia
Types 2A and 2B 1578
35
Sarcomas of the Soft Tissues and Bone 1581
section 1 Soft Tissue Sarcoma 1581
MURRAY F. BRENNAN
SAMUEL SINGER
ROBERT G. MAKI
BRIAN O SULLIVAN
Incidence 1587
liv Contents
Etiology and Genetics 1581
Distribution 1584
Pathologic Classification 1584
Grading of Sarcoma 1587
Differential Diagnosis 1588
Clinicopathologic Features of Specific Types of Benign and Malignant
Soft Tissue Tumors 1589
Clinical Presentation 1597
Differential Diagnosis 1597
Management of Extremity and Superficial Truncal Soft Tissue
Sarcoma 1602
Radiation Therapy 1603
Adjuvant Brachytherapy 1608
Special Considerations 1609
Definitive Radiation 1610
Adjuvant Chemotherapy 1611
Preoperative Chemotherapy 1616
Intraarterial Chemotherapy 1617
Hyperthermia and Limb Perfusion 1617
Special Features of the Management of Sarcomas of
Nonextremity Sites 1618
Serious Complications of Primary Treatment 1620
Prognostic Factors 1622
Quality of Life and Functional Outcome 1623
Treatment of Local Recurrence 1623
Management of Advanced Disease 1624
Resection of Metastatic Disease 1624
Systemic Therapy for Advanced Disease 1624
Response by Histologic Subtype and Site 1629
Recommendations for Patients with Advanced
Disease 1631
Future Directions 2632
section 2 Sarcomas of Bone 1638
MARTIN M. MALAWER
LEE J. HELMAN
BRIAN O SULLIVAN
Classification and Types of Bone Tumor 1638
Radiographic Evaluation and Diagnosis 2639
Natural History 2640
Staging Bone Tumors 2642
Preoperative Evaluation 2642
Biopsy Technique and Timing 2644
Restaging after Induction (Preoperative) Chemotherapy 2645
Surgical Management of Skeletal Tumors 2646
Principles and Techniques of Limb Sparing Surgery 2647
Limb Sparing Surgery and Perioperative Pain Management 1648
Amputations 1652
Cryosurgery 2652
Chemotherapy for Bone Sarcomas 2652
Radiotherapy for Bone Tumors 2658
Malignant Bone Tumors 2 660
Conlnit.s Iv
36
Benign and Malignant Mesothelioma 1687
HARVEY I. PASS
NICHOLAS J. VOGELZANG
STEPHEN M. HAHN
MICHELE CARBONE
Mechanism of Asbestos Induced Oncogenesis 1687
Mechanism of Asbestos Pathogenicity 1688
Overview of Molecular Mechanisms in Mesothelioma 1688
Simian Virus 40 1690
Radiation and Mesothelioma 1690
Genetic Predisposition to Mesothelioma 1690
Pathology of Mesothelioma 1691
Solitary Fibrous Tumors of Pleura 1693
Clinical Presentation of Malignant Pleural Mesothelioma 1693
Diagnostic Approach 1698
Natural History 1699
Prognostic Indicators 1699
Staging 1700
Treatment 1700
Malignant Peritoneal Mesothelioma 1710
Malignant Mesothelioma of the Tunica Vaginalis Testis 1712
Malignant Mesothelioma of the Pericardium 1712
37
Cancer of the Skin 1717
SUMAIRA Z. AASI
DAVID J.LEFFELL
Diagnosis 2727
General Approach to Management of Skin Cancer 1718
Precancerous Lesions 1723
Carcinoma Metastatic to Skin 2 742
Conclusion 2742
38
Melanoma 1745
suction 1 Molecular Biology of Cutaneous Melanoma 1745
ZHAO JUN LIU
MEENHARD HERLYN
Etiology of Melanoma 2745
Genetics of Melanoma 2746
Biologic Basis of Melanoma Development and Progression 2 749
section 2 Cutaneous Melanoma 1754
CHARLES M. BALCH
MICHAEL B. ATKINS
ARTHUR J. SOBER
Epidemiology 2754
Ivi Contents
Anatomic Distribution 1755
Risk Factors 1756
Prevention and Screening 2757
Diagnosis of Melanoma 1759
Prognostic Factors 1760
New Staging System for Melanoma 1765
Biopsy 1769
Surgical Treatment of Primary Melanoma (Stages I to III) 1769
Local Recurrences 1774
Management of Regional Nodes—Lymphadenectomy
(Stage III) 1774
Radiotherapy for Regional Metastases (Stage III) 1778
Regional Relapses 1779
Adjuvant Systemic Therapy (Stages II and III) 1780
Follow Up of Melanoma Patients (Stages I to III) 1786
Diagnosis of Stage IV Melanoma 1786
Surgery and Irradiation for Distant Metastases (Stage IV) 1787
Systemic Treatment of Stage IV Melanoma 1792
section 3 Intraocular Melanoma 1809
ROBERT B. AVERY
MINESH P. MEHTA
RICHARD M. AUCHTER
DANIEL M. ALBERT
Epidemiology 1809
Mortality 1810
Natural History 1810
Etiology and Pathogenesis 1811
Histopathology 1812
Diagnosis 1813
Prognostic Assessment 1815
Therapeutic Approaches 1816
Radiation Therapy 1817
Management 1823
Future Directions 1824
39
Neoplasms of the Central Nervous System 1827
skctio* 1 Molecular Biology of Central Nervous System Neoplasms 1827
DAVID N. LOUIS
WEBSTER K. CAVENEE
Diffuse, Fibrillary Astrocytomas 1827
Other Gliomas 2 £29
Medulloblastomas 1831
Meningiomas 1831
Peripheral Nerve Tumors 1832
Miscellaneous Tumors 1832
Neurologic Tumor Syndromes 1832
Conclusion 1833
Contents I H
section 2 Neoplasms of the Central Nervous System 1834
HOWARD A. FINE
FRED G. BARKER II
JAMES M. MARKERT
JAY S. LOEFFLER
General Considerations 1834
Anatomic and Clinical Considerations 1836
Neurodiagnostic Tests 1838
Surgery 1841
Radiation Therapy 1843
Chemotherapy 1845
Cerebral Astrocytomas 2847
Brainstem Gliomas 1854
Cerebellar Astrocytomas 1856
Optic, Chiasmal, and Hypothalamic
Gliomas 1856
Oligodendrogliomas 1858
Ependymomas 1860
Meningiomas 1862
Primitive Neuroepithelial Tumors 1865
Medulloblastomas 1865
Pineal Region Tumors 1869
Pituitary Adenomas 1871
Craniopharyngiomas 1873
Acoustic Neuromas (Vestibular Schwannomas) 7874
Glomus Jugulare Tumors 1875
Chordomas and Chondrosarcomas 1876
Hemangioblastomas 1877
Choroid Plexus Papillomas and
Carcinomas 1879
Spinal Axis Tumors 1880
40
Cancers of Childhood 1889
section 1 Molecular Biology of Childhood Cancers 1889
LEE J. HELMAN
DAVID MALKIN
Tumor Suppressor Genes 1890
Retinoblastoma: The Paradigm 1890
Wilms Tumor: Three Distinct Loci 1891
Neurofibromatoses 1892
Neuroblastoma 1892
Ewing s Sarcoma Family of Tumors 1893
Rhabdomyosarcoma 1893
Hereditary Syndromes Associated with Tumors of
Childhood 1894
Predictive Testing for Germline Mutations and Childhood
Cancers 1895
Molecular Therapeutics 1895
lviii Contents
sKcno 2 Solid Tumors of Childhood 1898
DAVID H. EBB
DANIEL M. GREEN
ROBERT C. SHAMBERGER
NANCY J. TARBELL
Epidemiology 1898
Management of Childhood Cancer 1898
Wilms Tumor 1898
Favorable Histology Wilms Tumor 1903
Neuroblastoma 1904
Retinoblastoma 1909
Advanced Unilateral Disease 1911
Limited Unilateral or Limited Bilateral
Disease 1911
Bilateral Disease 1911
Chemotherapy 1912
Rhabdomyosarcoma 1912
Ewing s Sarcoma and Peripheral Primitive Neuroectodermal
Tumor 1919
Primary Hepatic Tumors 1923
Germ Cell Tumors 1926
Clinical Presentation and Treatment by Anatomic
Site 1928
41
Lymphomas 1939
section 1 Leukemias and Lymphomas of Childhood 1939
HOWARD J. WEINSTEIN
NANCY J. TARBELL
Leukemias 1939
Non Hodgkin s Lymphoma 1948
Hodgkin s Disease 1953
section 2 Non Hodgkin s Lymphomas 1957
RICHARD I. FISHER
PETER M. MAUCH
NANCY LEE HARRIS
JONATHAN W. FRIEDBERG
Epidemiology 1957
Etiology 1958
Biologic Background for Classification of Lymphoid
Neoplasms 1959
Principles of the Revised European American Classification of Lymphoid Neoplasms/
World Health Organization Classification of Lymphoid
Neoplasms 1967
Principles of Management of Non Hodgkin s
Lymphoma 2969
Specific Disease Entities 1971
Special Clinical Situations 1990
Contents H
si ;ctio 3 Cutaneous T Cell Lymphomas 1998
LYNN D. WILSON
GLENN W. JONES
MICHAEL GIRARDI
RICHARD L. EDELSON
PETER W. HEALD
Pathobiology 1998
Epidemiology 1998
Etiology 1998
Clinical Presentation 1999
Approach to the Patient with Mycosis Fungoides 2000
Patient Evaluation 2002
Principles of Therapy 2003
Other Clinical Management Issues 2010
section 4 Primary Central Nervous System Lymphoma 2012
LISA M. DEANGELIS
JOACHIM YAHALOM
Clinical Features 2012
Diagnostic Tests 2013
Pathology 2013
Management and Therapy 2014
Immunologically Normal Patients 2015
Immunocompromised Patients 2079
suction 5 Hodgkin s Lymphoma 2020
VOLKER DIEHL
NANCY LEE HARRIS
PETER M. MAUCH
History 2020
Etiology and Epidemiology 2021
Biology and Cell of Origin 2021
Pathology 2026
Diagnosis and Staging 2032
Clinical Presentation 2034
Treatment Methods 2035
Choice of Treatment 2038
Special Cases 2059
Sequelae 2062
Quality of Life 2064
New Drugs for Treatment of Hodgkin s Lymphoma 2064
Immunotherapy 2065
Gene Therapy 2068
42
Acute Leukemias 2077
sectios i Molecular Biology of Acute Leukemias 2077
D. GARY GILLILAND
GLEN DAVID RAFFEL
Leukemic Stem Cell 2077
l Contents
Recurring Chromosomal Abnormalities in Acute Leukemia 2078
Deletions and Numeric Abnormalities in Acute Leukemias 2083
Chromosomal Translocations That Result in Overexpression of
Otherwise Normal Genes 2084
Point Mutations in Acute Leukemia 2084
Mutational Complementation Groups in Acute Leukemias 2085
Conclusion 2086
suction 2 Management of Acute Leukemias 2088
DAVID A. SCHEINBERG
PETER G. MASLAK
MARK A. WEISS
Epidemiology and Etiology 2088
Biology of Acute Leukemias 2090
Diagnosis and Classification of Acute Leukemias 2091
Principles of Clinical Management of Acute Myelogenous
Leukemia 2098
Treatment of Newly Diagnosed Acute Myelogenous
Leukemia 2100
Induction 2100
Treatment of Relapsed Acute Myelogenous
Leukemia 2106
Conclusion 2115
43
Chronic Leukemias 2121
section 1 Chronic Myelogenous Leukemia 2121
BRIAN J. DRUKER
STEPHANIE J. LEE
Epidemiology 2121
Pathogenesis 2222
Diagnosis and Clinical Course 2223
Treatment of Chronic Phase Disease 2224
Advanced Phase Disease 2230
Future Directions 2232
suction 2 Chronic Lymphoid Leukemias 2133
SUSAN O BRIEN
MICHAEL J. KEATING
Molecular Biology 2233
Immune Abnormalities 2235
Diagnosis 2135
Clinical Manifestations 2235
Treatment and Response Criteria 2138
Biologic Therapies 2240
Second Malignancies and Transformation 2242
Prolymphocytic Leukemia 2242
Large Granular Lymphocyte Leukemia 2242
Hairy Cell Leukemia 2242
Ciinlnils l i
suction 3 Myelodysplastic Syndromes 2144
STEFAN FADERL
HAGOP M. KANTARJIAN
Incidence and Epidemiology 2144
Etiology 2144
Classification and Prognostic Factors 2145
Biology and Pathophysiology of Myelodysplastic Syndromes 2146
Clinical Manifestations 2148
Laboratory Features 2148
Differential Diagnosis 2148
Subtypes of Myelodysplastic Syndromes 2148
Therapy of Myelodysplastic Syndromes 2149
Conclusion 2153
44
Plasma Cell Neoplasms 2155
NIKHIL C. MUNSHI
KENNETH C. ANDERSON
History 2255
Epidemiology 2156
Etiology: Environmental Exposure 2156
Pathogenesis 2157
Clinical Manifestations 2163
Diagnosis 2165
Differential Diagnosis 2168
Prognostic Variables 2170
Treatment 2172
Waldenstrom s Macroglobulinemia 2181
45
Paraneoplastic Syndromes 2189
SUSANNE M. ARNOLD
FRANK S. LIEBERMAN
KENNETH A. FOON
Endocrinologic Manifestations of Cancer 2189
Hematologic Manifestations of Cancer 2193
Gastrointestinal Manifestations of Cancer 2196
Renal Manifestations of Nonrenal Cancer 2797
Cutaneous Manifestations of Cancer 2197
Neurologic Manifestations of Cancer 2200
Miscellaneous Paraneoplastic Syndromes 2207
46
Cancer of Unknown Primary Site 2213
F. ANTHONY GRECO
JOHN D. HAINSWORTH
Poorly Differentiated Neoplasms of Unknown Primary Site 2214
lvii Contents
Poorly Differentiated Carcinoma (with or without Features of Adenocarcinoma)
of Unknown Primary Site 2216
Neuroendocrine Carcinoma of Unknown Primary Site 2221
Adenocarcinoma of Unknown Primary Site 2222
Squamous Carcinoma of Unknown Primary Site 2225
Chemotherapy for Metastatic Carcinoma of Unknown Primary Site 2226
Special Issues in Carcinoma of Unknown Primary Site 2229
Conclusion 2232
47
Peritoneal Carcinomatosis 2237
JAMES F. PINGPANK, JR.
Pathophysiology 2237
Diagnostic Evaluation 2238
Histologic Subtypes 2238
Treatment 2242
48
Immunosuppression Related Malignancies 2247
section 1 AIDS RelatedMalignancies 2247
ROBERT YARCHOAN
RICHARD F. LITTLE
Kaposi s Sarcoma 2247
AIDS Associated Lymphomas 2253
Primary Central Nervous System Lymphoma in AIDS 2258
Hodgkin s Disease 2259
Anogenital Cancers in Human Immunodeficiency Virus
Infection 2259
Future Directions 2260
section 2 Transplantation Related Malignancies 2263
STANLEY R. RIDDELL
Immune Surveillance and Tumor Development 2263
Hematopoietic Stem Cell Transplant Recipients 2263
Organ Transplant Recipients 2267
49
Oncologic Emergencies 2273
sEcmn I Superior Vena Cava Syndrome 2273
JOACHIM YAHALOM
Anatomy and Pathophysiology 2273
Etiology and Natural History 2273
Diagnostic Procedures 2275
Management 2276
Caiiifiiis Iviii
Treatment 2277
Recommendations 2279
section 2 Increased Intracranial Pressure 2281
JOACHIM M. BAEHRING
Pathophysiologic Considerations 2281
Epidemiology and Pathogenesis 2281
Clinical Presentation 2282
Diagnosis 2284
Treatment 2286
section 3 Spinal Cord Compression 2287
JOACHIM M. BAEHRING
Epidemiology 2287
Pathophysiology 2287
Clinical Presentation 2289
Differential Diagnosis 2290
Diagnosis 2290
Treatment 2291
Prognosis 2291
Conclusion 2292
section 4 Metabolic Emergencies 2292
ANTONIO TITO FOJO
Tumor Lysis Syndrome 2292
Hyperuricemia 2294
Cancer and Hyponatremia 2295
Lactic Acidosis and Cancer 2296
Hypercalcemia and Cancer 2297
Cancer Related Hemolytic Uremic Syndrome 2299
section 5 Urologic Emergencies 2301
JONATHAN A. COLEMAN
MCCLELLAN M. WALTHER
Urinary Tract Infection 2301
Cystitis 2301
Bladder Hemorrhage 2304
Urinary Obstruction 2305
Priapism 2307
Paraphimosis 2307
50
Specialized Techniques in Cancer Management 2309
section 1 Vascular Access and Specialized Techniques of Drug Delivery 2309
JAMES F. PINGPANK, JR.
Catheter Types 2309
Catheter Selection 2312
Insertion Techniques 2312
Catheter Related Complications 2314
suction 2 Isolation Per fusion 2316
H. RICHARD ALEXANDER, JR.
Principles of Isolation Perfusion 2316
Results of Isolation Perfusion 2318
Current Status of Isolated Limb Perfusion 2319
Current Status of Isolated Hepatic Perfusion 2321
Status of Isolation Perfusion of Other Sites 2321
Variations of Isolation Perfusion Techniques 2321
Conclusion 2321
51
Treatment ofMetastatic Cancer 2323
section 1 Metastatic Brain Cancer 2323
DAVID A. LARSON
JAMES L. RUBENSTEIN
MICHAEL W. MCDERMOTT
Brain Metastases 2323
Carcinomatous Meningitis 2333
section 2 Metastatic Cancer to the Lung 2337
MICHAEL R. JOHNSTON
MARC DE PERROT
Biology 2337
Diagnosis 2337
Treatment 2339
Results 2346
section 3 Metastatic Cancer to the Liver 2352
H. RICHARD ALEXANDER, JR.
NANCY E. KEMENY
THEODORE S. LAWRENCE
Natural History of Liver Metastases 2353
Imaging of Hepatic Metastases 2354
Resection: Technical Considerations 2354
Results of Hepatic Resection for Colorectal Cancer 2355
Results of Resection for Noncolorectal Cancers 2355
Hepatic Arterial Chemotherapy 2356
Toxicity of Hepatic Arterial Infusion Therapy with
Floxuridine 2358
Other Agents Used with Hepatic Arterial Infusion 2359
Adjuvant Therapy after Resection of Colorectal
Liver Metastases 2359
Neoadjuvant Chemotherapy 2360
Other Liver Tumors 2360
Contents I.YV
Hepatic Artery Infusion with Hepatic Venous Filtration 2360
Isolated Hepatic Perfusion 2361
Chemoembolization for Metastatic Cancer to the Liver 2367
Local Ablative Therapy 2362
Cryotherapy 2363
Radiofrequency Ablation 2363
Other Ablative Techniques 2364
Results of Whole Liver Irradiation ± Chemotherapy 2365
Conclusion 2366
section 4 Metastatic Cancer to the Bone 2368
MARK W. MANOSO
JOHN H. HEALEY
Presentation 2368
Pathophysiology 2369
Diagnostic Evaluation 2369
Imaging of Bone Lesions 2370
Therapeutic Goals 2372
Therapeutic Modalities 2371
section 5 Malignant Pleural and Pericardia! Effusions 2381
DAO M. NGUYEN
DAVID S. SCHRUMP
Malignant Pleural Effusion 2381
Malignant Pericardial Effusion 2387
section 6 Malignant Ascites 2392
RICHARD B. HOSTETTER
FRANCESCO M. MARINCOLA
DOUGLAS J. SCHWARTZENTRUBER
Diagnosis and Workup 2392
Treatment of Malignant Ascites 2393
Conclusion 2396
52
Hematopoietic Therapy 2399
section 1 Transfusion Therapy 2399
YANYUN WU
PETER L. PERROTTA
EDWARD L. SNYDER
Blood Component Therapy 2400
Transfusion Reactions and Complications 2406
Transfusion Transmitted Disease 2409
Use of Special Blood Products in Oncology Patients 2410
Apheresis 242 2
Effect of Growth Factors on Transfusion Medicine 2422
Blood Substitutes 2422
sectio 2 Autologous Stem Cell Transplantation 2414
DENNIS L. COOPER
STUART SEROPIAN
History 2415
Stem Cell Mobilization 2425
Inadequate Mobilization of Stem Cells 2416
Tumor Contamination 2418
Practical Considerations for the Potential Autologous Stem Cell Patient 2419
High Dose Therapy Regimens: New Directions 2419
Late Toxicity: Myelodysplasia and Secondary Leukemia 2421
Future Directions 2421
section 3 Allogeneic Hematopoietic Stem Cell Transplantation 2423
RICHARD W. CHILDS
Conditioning Regimens 2424
Graft Versus Leukemia Effect 2425
Mechanisms of Graft Versus Leukemia Effect 2427
Complications of Allogeneic Hematopoietic Stem Cell Transplantation 2427
Epstein Barr Virus Lymphoproliferative Disorder 2429
Sources of Allogeneic Hematopoietic Stem Cells 2432
Results of Conventional Allogeneic Transplantation for Hematologic Malignancies 2434
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation 2435
Future Prospects 2439
section 4 Hematopoietic Growth Factors 2442
JENNIFER L. HOLTER
HOWARD OZER
Overview of Hematopoiesis and Hematopoietic Growth Factors 2442
Clinical Use of Recombinant Erythropoietin in Cancer Therapy 2448
Anemia Related to Myeloproliferative Disorders 2450
Predictors of Recombinant Erythropoietin Therapy Response 2451
Clinical Use of Recombinant Granulocyte Colony Stimulating Factors
in Cancer Therapy 2452
Clinical Use of Recombinant Interleukin 11 in Cancer Therapy 2455
Hematopoietic Growth Factors in Development 2456
Conclusion 2456
53
Infections in the Cancer Patient 2461
BRAHM H. SEGAL
THOMAS J. WALSH
JUAN C. GEA BANACLOCHE
STEVEN M. HOLLAND
Factors Predisposing Cancer Patients to Infection 2462
Bacterial Infections in Cancer Patients 2465
Fungal Infections 2469
Viral Infections 2477
Parasitic Infections 2484
Contents Iwii
Neutropenic Fever 2486
Syndromes 2496
Immune Augmentation Strategies 2506
54
Adverse Effects of Treatment 2515
section 1 Nausea and Vomiting 2515
ANN M. BERGER
REBECCA A. CLARK SNOW
Nature of the Problem 2515
Pathophysiology of Nausea and Vomiting 2515
Emetic Syndromes 2517
Control of Emesis and Risk Factors 2518
Antiemetic Agents 2519
Treatment Options Based on Emesis Category 2520
New Agents 2520
Radiation Induced Nausea and Vomiting 2521
Nausea and Vomiting Secondary to Comorbid Conditions 2522
Improving Antiemetic Control 2522
section 2 Oral Complications 2523
ANN M. BERGER
JANE M. FALL DICKSON
Oral Complications 2523
Sequelae of Oral Complications 2525
Strategies for Prevention and Treatment of Oral Complications 2526
Future Research Directions 2533
Conclusion 2533
section 3 Pulmonary Toxicity 2535
DIANE E. STOVER
ROBERT J. KANER
Radiation Induced Pulmonary Toxicity 2535
Radiation Related Bronchiolitis Obliterans with Organizing Pneumonia 2538
Chemotherapy Induced Pulmonary Toxicity 2539
section 4 Cardiac Toxicity 2545
JOACHIM YAHALOM
CAROL S. PORTLOCK
Anthracyclines 2545
Mitoxantrone 2547
Cyclophosphamide 2547
Ifosfamide 2547
Taxanes 2547
Trastuzumab 2548
Fluoropyrimidines 2549
Radiation Induced Heart Disease 2549
Conclusion 2553
section 3 Hair Loss 2556
ANN M. BERGER
JOYSON KARAKUNNEL
Anatomy and Physiology 2556
Classification 2556
Staging 2557
Diagnosis 2557
Treatment 2557
Conclusion 2559
section 6 Gonadal Dysfunction 2560
MARVIN L. MEISTRICH
RENA VASSILOPOULOU SELLIN
LARRY I. LIPSHULTZ
Effects of Cytotoxic Agents on Adult Men 2560
Effects of Cytotoxic Agents on Adult Women 2563
Effects of Cytotoxic Agents on Children 2566
Gonadal Dysfunction after Cranial Irradiation 2566
Preservation of Fertility, Hormone Levels, and Sexual Function 2567
Prevention and Management of Erectile and Ejaculatory Dysfunction 2570
Genetic Concerns 2571
Counseling 2572
section 7 Second Cancers 2575
FLORA E. VAN LEEUWEN
LOIS B. TRAVIS
Methods to Assess Second Cancer Risk 2575
Carcinogenicity of Individual Treatment Modalities 2576
Risk of Second Malignancy in Patients with Selected Primary Cancers 2580
Conclusion 2598
sectio 8 Miscellaneous Toxicities 2602
RAYMOND B. WEISS
Neurotoxicity 2603
Nephrotoxicity 2607
Hepatotoxicity 2610
Hypersensitivity Reactions 2611
Vascular Toxicity 2612
55
Supportive Care and Quality of Life 2615
section 1 Management of Cancer Pain 2615
KATHLEEN M. FOLEY
Epidemiology 2615
Barriers to Cancer Pain Management 2616
Definition of Pain 2617
Anatomy and Physiology of Pain 2617
Types of Pain 2618
Temporal Aspects of Pain 2619
Contents l i
Intensity of Pain 2619
Measurement of Pain 2619
Classification of Patients with Cancer Pain 2621
Common Pain Syndromes 2624
Clinical Assessment of Pain 2624
Management of Cancer Pain 2627
Analgesic Drug Therapy 2627
Classes of Drugs 2630
Psychological Approaches 2639
Anesthetic and Neurosurgical Approaches 2639
Physiatric Approaches 2645
Sedation in the Imminently Dying 2645
Algorithm for Cancer Pain Management 2646
Future Directions 2646
section 2 Nutritional Support 2649
J. STANLEY SMITH
DAVID FRANKENFIELD
WILEY W. SOUBA
Dysgeusia 2649
Weight Loss and Cancer Cachexia 2650
Nutrition Support for Weight Loss and Cancer Cachexia 2651
Nutrition and Tumor Growth 2651
Nutritional Assessment of the Cancer Patient 2652
Indications for Nutrition Support 2652
Parenteral versus Enteral Nutrition in Cancer Patients 2652
Specific Indications for the Use of Total Parenteral Nutrition in the
Cancer Patient 2653
Improving the Efficacy of Current Feeding Regimens 2658
Techniques of Providing Nutritional Support 2659
Conclusion 2661
section 3 Sexual Problems 2662
PATRICIA A. GANZ
MARK S. LITWIN
BETH E. MEYEROWITZ
Sexual Health and Physiology 2662
Sexual Problems and Their Prevalence among the General Population 2663
Impact of Cancer and Its Treatment on Sexual Health 2664
Specific Treatments 2665
Sexual Problems Associated with Specific Cancers 2668
Strategies for Assessment and Intervention 2671
Conclusion 2673
section 4 Genetic Counseling 2676
ELLEN T. MATLOFF
Why Is Cancer Genetic Counseling Necessary? 2676
Who Is a Candidate for Cancer Genetic Counseling? 2677
Components of the Cancer Genetic Counseling Session 2677
Issues in Cancer Genetic Counseling 2680
Future Directions 2681
IXX Contents
section 5 Psychological Issues 2683
BETH L. DINOFF
JOHN L. SHUSTER
Phases of Illness 2683
Psychological Complications of Cancer 2685
Therapies 2688
section 6 Community Resources 2691
BONNIE A. INDECK
Initial Diagnosis of Cancer 2691
Social Support Network 2691
Emotional Support 2691
Information Support 2693
Internet 2693
Computer Groups 2694
Instrumental Support 2694
Trends Affecting Demand for Community Services 2695
Survivorship 2696
Appendix: Common Community Resources 2696
section 7 Specialized Care of the Terminally III 2702
JANET L. ABRAHM
Discussing Prognosis 2702
Advance Care Planning 2703
Hope 2703
Barriers That Inhibit Advance Care Planning
Discussions 2704
Curiosity 2704
Healing versus Curing 2704
How to Tell the Children 2 704
Cultural/Religious Considerations 2705
Care without Chemotherapy 2706
Palliative Care Program 2706
Hospice Programs 2707
Relief of Suffering 2708
The Final Days 2714
After the Death 2715
Grief and Bereavement 2725
Conclusion 2717
56
Rehabilitation of the Cancer Patient 2719
LYNN H. GERBER
MARY M. VARGO
REBECCA G. SMITH
Impact of Cancer Treatment on Function 2720
Rehabilitation Interventions 2725
Contents
Rehabilitation Hospitalization and Basic Functional Independence 2732
Vocational Issues 2733
Rehabilitation Treatments of Specific Tumors 2734
57
Societal Issues in Oncology 2747
section 1 Ethical Issues 2747
CHRISTOPHER K. DAUGHERTY
Ethical Issues in Clinical Care in Oncology 2747
Ethical Issues in Cancer Clinical Trials 2752
Conclusion 2757
section 2 Economic Issues 2759
ALBERT B. EINSTEIN, JR.
U.S. Health Care Economy 2759
Medicare Cost Containment Efforts 2759
Medicare Reimbursement for Cancer Services 2760
Medicaid Cost Containment Efforts 2767
Insurance Industry Cost Containment Efforts 2767
Hospital Economic Issues 2762
Physician Economic Issues 2762
National Cancer Institute Designated and University Cancer Centers
Economic Issues 2763
Clinical Research 2763
Impact of Genomics 2764
Complementary and Alternative Medicine 2765
Standardization of Practice 2765
Health Economics and the Economic Burden of Cancer 2765
The Future 2766
section 3 Regulatory Issues 2767
GRANT A. WILLIAMS
PATRICIA KEEGAN
NEIL R. P. OGDEN
RICHARD PAZDUR
ROBERT TEMPLE
MARK MCCLELLAN
History of U.S. Food and Drug Administration Regulation of Drugs
and Biologies 2767
U.S. Food and Drug Administration Oversight of Clinical Trials for
Drugs and Biologies 2768
Basis for Cancer Drug Approval 2769
Drug Safety Reporting and Evaluation 2773
Access to Investigational Drugs 2773
Biologic Drug Products: Special Considerations 2773
Regulation of Devices for Cancer Treatment and Diagnosis 2774
U.S. Food and Drug Administration Initiatives and Guidances Expediting
Approval of Cancer Drugs, Biologies, and Devices 2776
Ixxii Contents
section 4 Telemedicine 2777
RICHARD M. SATAVA
JONATHAN D. LINKOUS
JAY H. SANDERS
Applications of Telemedicine 2778
Telemedicine in Other Countries 2779
Telemedicine in Oncology Care—Current Practices 2779
Telesurgery 2779
Telemedicine Impact on National Medical Policy 2780
Barriers and Challenges 2780
Conclusion 2781
section 5 International Differences in Oncology 2782
OLIVIER RIXE
PETER HARPER
DAVID KHAYAT
Developing Nations 2782
Cancers and Mortality: Differences in the More Developed Countries 2782
Screening 2783
Anticancer Drug Development throughout the World 2784
Drug Approval Process 2784
Cancer Treatment Strategy: European and United States Differences 2784
Differences in Cancer Survival 2784
Access to Cancer Care in Developed Nations 2785
Training as an Oncologist 2786
Research 2786
Truth Telling : Differences between Nations 2786
Cancer in the Elderly 2787
Conclusion 2787
section 6 The National Cancer Program 2788
ANDREW C. VON ESCHENBACH
National Cancer Institute as Steward of the National Cancer
Program 2789
Harnessing the Power of Molecular Epidemiology 2789
Developing an Integrative Understanding of Cancer Biology 2790
Providing Bioinformatics Infrastructure 2790
Developing Prevention, Early Detection, and Prediction Approaches 2790
Facilitating the Development of Cancer Interventions 2791
Creating an Integrated Clinical Trials System 2792
Overcoming Health Disparities 2791
A Critical Enterprise Wide Opportunity: Technology Development and
Integration 2792
Integrative Computational Biology and Bioinformatics 2792
Advanced Imaging 2792
Bioengineering and Advanced Prototyping 2792
Development and Preclinical Testing of Prevention and Therapeutic
Agents 2792
Shared Research Resources 2793
Conclusion 2793
Contents lv iii
58
Information Systems in Oncology 2795
DANIEL R. MASYS
The Internet 2796
Electronic Medical Records 2799
Conclusion 2802
59
Complementary, Alternative, and Integrative Therapies in Cancer Care 2805
ETHAN M. BASCH
CATHERINE E. ULBRICHT
Background 2805
Safety Concerns 2806
Patient Clinician Communication 2808
Specific Complementary and Alternative Medicine Therapies 2809
Therapies Used for Cancer Treatment and Secondary Prevention 2809
Therapies Used for Supportive Care 2812
Therapies Used for Primary Cancer Prevention 2813
part4t
NEWER APPROACHES IN CANCER TREATMENT
60
Gene Therapy 2819
PATRICK HWU
Methods of Gene Transfer 2819
Gene Marking Studies 2824
Genetic Modification of the Immune Response 2826
Modification of Tumors with Genes That Have Direct Antitumor Effects 2830
Selective Replication of Virus in Tumors 2832
Introduction of Genes into Normal Tissues to Protect Them from Chemotherapy or Radiotherapy 2832
Antiangiogenic Gene Therapy 2833
Molecular Imaging of Gene Modified Cells 2834
Conclusion 2834
61
Cancer Vaccines 2839
section 1 Preventive Vaccines 2839
DOUGLAS R. LOWY
JOHN T. SCHILLER
Background 2839
lx iv Contents
Infectious Agents and Cancer 2839
Prophylactic versus Therapeutic Vaccination 2841
Hepatitis B Virus 2842
Human Papillomavirus 2843
Helicobacter pylori 2845
secti() 2 Therapeutic Vaccines 2846
NICHOLAS P. RESTIFO
JONATHAN J. LEWIS
Elicitation of Tumor Specific Immune Responses 2846
Identification of Tumor Associated Antigens Suitable for
Therapeutic Targeting 2846
Enhancement of Tumor Antigen Immunogenicity by Modification of
Epitope Sequences 2847
Early Models Using Therapeutic Cancer Vaccines 2848
Consistent Increases in Tumor Specific T Cells without Consistent
Clinical Responses 2848
How Are We Doing in Clinical Trials? 2848
Lessons from Melanoma 2849
Clinical Trial Data 2850
Immune Responses Do Not Always Translate into Clinical Responses—
Proposed Mechanisms of Tumor Escape 2853
Future Directions: A Focus on T Cell Activation and Death 2853
Conclusion 2854
62
Cell transfer Therapy 2857
MARK E. DUDLEY
STEVEN A. ROSENBERG
Background 2857
Preclinical Studies of Adoptive Cell Transfer 2858
Clinical Trials 2858
Tumor Infiltrating Lymphocytes 2860
Adoptive Cell Transfer Therapy after Lymphodepleting Chemotherapy in Patients
with Melanoma 2860
Additional Studies 2862
63
Antiangiogenesis Agents 2865
JUDAH FOLKMAN
Angiogenic Switch 2865
Endogenous Angiogenesis Inhibitors 2867
Rationale for Antiangiogenic Therapy of Cancer 2867
Antiangiogenic (Metronomic) Chemotherapy 2869
Future Directions 2879
Ciiiilnils l
64
Focused Ultrasound 2883
FERENC A. JOLESZ
KULLERVO H. HYNYNEN
Fundamental Principles of Focused Ultrasound Surgery 2883
Interaction between Tissue and the Ultrasound Beam 2884
Magnetic Resonance Imaging Guidance for Thermal Ablations 2884
Magnetic Resonance Imaging Guided Focused Ultrasound Therapy
Delivery Systems 2885
Clinical Applications 2886
Conclusion 2889
65
Antisense Inhibition of Gene Expression 2891
C. A. STEIN
LUBA BENIMETSKAYA
SRIDHAR MANI
Oligonucleotide Stability and Efficacy: The Role of Phosphorothioates 2892
Mechanism of Action of the Antisense Effect 2894
Delivery of Oligonucleotides into Cells 2895
Pharmacokinetics 2896
Clinical Studies 2896
Clinical Trials of G3139 2897
Index 1 1
|
| adam_txt |
CONTENTS
PART M
MOLECULAR BIOLOGY OF CANCER
1
Molecular Methods In Oncology section 1 Amplification Techniques 3
PAUL M. LIZARDI
Improved Analysis of Mutations in Oncogenes and Tumor
Suppressor Genes 3
Highly Parallelized Single Nucleotide Polymorphism Assays Can Also Be
Used for Somatic Genotyping 4
Increasing the Accuracy of Sequence Information Derived from Polymerase
Chain Reaction Amplification 5
Multiplex Real Time Polymerase Chain Reaction Amplification for Detection
of Minimal Residual Disease or Viral Load 5
Mutation Detection Using In Situ Hybridization Methods Coupled with
DNA Amplification 5
High Throughput Methods for Measuring Gene
Dosage Alterations 6
Whole Genome Amplification of Microdissected Tissue 6
Amplification of Genomic Representations for Analysis of Gene
Gain/Loss 6
Tumor Classification Using Real Time Polymerase Chain Reaction to
Measure Messenger RNA Levels 6
XXX Contents
Biomarker Detection Using DNA Amplified Immunoassays 7
Amplification Based Approaches for DNA Methylation Analysis
in Cancer 7
suction 2 RNA Interference 8
RICHARD A. MORGAN
Biochemistry and Function 8
RNA Interference in Mammals 10
Cancer Applications 11
section 3 cDNA Arrays 13
KEVIN M. BROWN
INGRID A. HEDENFALK
JEFFREY M. TRENT
DNA Microarrays and the Molecular Profiling of
Human Cancers 13
Microarray Technology 13
Pediatric Acute Lymphoblastic Leukemia 15
Diffuse Large B Cell Lymphoma 18
Breast Cancer 19
Microarrays, Tumor Aggressiveness, and Metastasis 21
Are DNA Microarrays Ready for Routine Clinical Management of
Patients with Cancer? 22
Concluding Remarks 24
section 4 Tissue Arrays 26
MARISA DOLLED FILHART
DAVID L. RIMM
Tissue Microarray Construction 26
Tissue Microarray Visualization 28
Tissue Microarray Analysis 29
Tissue Microarray Applications 32
section 5 Cytogenetics 34
MAZIN B. QUMSIYEH
YESIM YILMAZ
Chromosome Structure and Function 34
Cytogenetic Methods 36
Chromosome Abnormalities in Cancer 38
Data Mining in Cancer Cytogenetics 42
sectio\ 6 Bioinformatics 43
KENNETH H. BUETOW
"Flavors" of Bioinformatics 44
Biomedical Informatics 44
Electronic Information Provisioning 44
In Silico Biomedical Applications 46
The Future 50
Conti'nls vwi
2
Genomics and Proteomics 51
KATHERINE R. CALVO
EMANUEL F. PETRICOIN III
LANCE A. LIOTTA
Understanding Cancer at the Molecular Level: An Evolving Frontier 51
Genetic Mechanisms of Cancer Progression 51
Postgenome Challenge for Molecular Medicine 57
Tissue Microdissection Technology Brings Molecular Analysis to the Tissue Level 58
Complementary DNA Microarrays As a Tool to Analyze Gene Expression Patterns in Human Cancer 59
Beyond Functional Genomics to Cancer Proteomics 63
Molecular Diagnostics and Individualized Cancer Therapy 63
Serum Proteomics 67
3
Molecular Targets in Oncology. 73
section 1 Signal Transduction Systems 73
CHRISTOPHER L. CARPENTER
LEWIS C. CANTLEY
Sensory Machinery: Ligands and Receptors 73
Propagation of Signals to the Cell Interior 76
Efficiency and Specificity: Formation of Multiprotein Signaling Complexes SO
Regulation of Protein Levels: Transcription, Translation, and Proteolysis SI
section 2 Cell Cycle 83
STEVEN I. REED
Cell Cycle Engine 83
Regulation of the Cell Cycle 87
Cell Cycle and Cancer 90
Cell Cycle As a Target for Therapy 93
Conclusion 94
section 3 Apoptosis 95
SANDRA S. ZINKEL
STANLEY J. KORSMEYER
Genetics of Cell Death 95
Bcl 2 Family 95
Critical Role of Apoptosis in Tissue Homeostasis 98
Caspases 99
Death Receptors 99
Apoptosome 99
Inhibitors of Apoptosis 101
Role of Intracellular Organelles: Mitochondria and Endoplasmic Reticulum 101
Cell Proliferation and Apoptosis 101
Possibilities for Therapeutic Intervention 102
Conclusion 102
YY.vii Con/mis
sKcnos 4 Telomerase 105
KWOK KIN WONG
RONALD A. DEPINHO
Telomeres 105
Telomerase Structure, Regulation, and Function 106
Crisis, Telomerase Reactivation, and Alternative Lengthening of Telomeres 106
Telomere Maintenance and Cancer 107
Aging and Cancer 707
Telomere Dynamics, Inflammatory Diseases, and Cancer 108
Telomere Status as a Biomarker for Cancer 109
Telomerase and Telomere Maintenance As Therapeutic Targets 109
Rational Clinical Trial Designs of Telomere and Telomerase
Based Therapeutics 111
4
Invasion and Metastases 113
WILLIAM G. STETLER STEVENSON
Tumor Progression and Genetic Instability 113
Origins of Metastatic Tumor Cells 114
Microarray Analysis of Tumor Progression and Metastasis 115
Tumorigenesis and Metastasis Are Under Separate Genetic Control: Tumor Suppressor Genes 116
Metastatic Cascade 117
Tumor Microenvironment: Determinant of Metastatic Potential and Site of Metastasis 118
Tumor Cell Motility 119
Tumor Invasion of the Basement Membrane 119
Initiation of Cell Migration 119
Cell Cell Adhesion: Metastasis Suppressor 120
Cell Matrix Interactions and Tumor Cell Migration 121
Role of CD44 in Tumor Invasion and Metastasis 121
Role of Integrins in Tumor Progression 722
Cell Migration 724
Proteases in Tumor Cell Invasion 725
Conclusion 726
5
Angiogenesis 129
ISAIAH J. FIDLER
ROBERT R. LANGLEY
ROBERT S. KERBEL
LEE M. ELLIS
Neoplastic Angiogenesis 129
Phenotypic Diversity of Organ Specific Endothelial Cells 131
Tumor Vasculature 752
Host Mediated Angiogenesis 752
Overview of Antiangiogenic and Antivascular Therapies 133
Antivascular Therapy for Bone Metastasis 134
Clinical Studies of Imatinib 755
Discrepancy between Results of Preclinical and Clinical Trials 755
Contents \V\iii
Basic Principles for Design of Clinical Trials of Antiangiogenic Agents / 3 5
Conclusion 136
6
Cancer Immunology 139
NICHOLAS P. RESTIFO
JOHN R. WUNDERLICH
Antitumor T Cells 140
Biologic Sources of Tumor Associated Antigens 140
Presentation of Tumor Antigens to T Cells 141
Role of Antigen Presenting Cells in Activating Antitumor T Cells 146
T Cell Recognition of Tumor Antigens 148
Maturation of Antitumor T Cells 149
Activation of Mature Antitumor T Cells 750
Activation States of Antitumor T Cells 154
* Functions of Mature Antitumor T Cells 155
Conclusion 157
part £
PRINCIPLES OF ONCOLOGY
7
Etiology of Cancer: Viruses 165
section 1 RNA Viruses 165
GARY L. BUCHSCHACHER JR
FLOSSIE WONG STAAL
Retroviruses: Background, Replication Cycle, and Molecular Genetics 165
Mechanisms of Retroviral Oncogenesis 166
Human T Lymphotropic Virus Type 1 168
Human T Lymphotropic Virus Type 2 169
Human Immunodeficiency Virus 169
Hepatitis C Virus 171
section 2 DNA Viruses 173
PETER M. HOWLEY
DON GANEM
ELLIOT KIEFF
Hepadnaviruses and Hepatocellular Carcinoma / 74
Papillomaviruses and Human Cancer 175
Epstein Barr Virus 180
Kaposi's Sarcoma Associated Herpesvirus 181
Simian Vacuolating Virus 40 and the Human Polyomaviruses 183
xxxiv Contents
8
Etiology of Cancer: Chemical Factors 185
STUART H. YUSPA
PETER G. SHIELDS
Nature of Chemical Carcinogens: Chemistry and Metabolism 185
Animal Model Systems and Chemical Carcinogenesis 186
DNA Repair Protects the Host from Chemical Carcinogens 187
Genetic Susceptibility to Chemical Carcinogenesis 187
Determination of Chemical Carcinogens for Humans and Population
Based Risk Assessment 187
Chemical Carcinogenesis and Cancer Risk 757
Tumor Suppressor Genes in Human Cancer 189
Tobacco Smoking and Cancer Risk 190
9
Etiology of Cancer: Tobacco Use 193
GRAHAM A. COLDITZ
LAURIE B. FISHER
Effects of Tobacco Use and Cessation on Cancer Risk 193
Effect of Tobacco Use on Cardiovascular Disease 196
Cigars, Pipes, and Smokeless Tobacco 196
Secondhand Tobacco Smoke 797
National Trends in Smoking Prevalence 797
Disparities in Active Tobacco Use and Cessation 797
Cigarette Product Modification—Harm Reduction 7 98
Tobacco and Nicotine Addiction 795
Role of the Clinician 7 98
Strategies for Tobacco Control 795
Conclusion 7 98
10
Etiology of Cancer: Physical Factors 201
ROBERT L. ULLRICH
Interactions of Radiation with Cells and Tissues 202
Ultraviolet Light 211
Asbestos 213
11
Epidemiology of Cancer 217
skctiox 1 Epidemiologic Methods 217
XIAOMEI MA
MARGARET A. TUCKER
Descriptive Studies 218
Contents \\\\
Analytic Studies 219
Interpretation of Epidemiologic Findings 222
3 Special Topic: Molecular and Genetic Epidemiology 22
section 2 Cancer Statistics 226
AHMEDIN JEMAL
ELIZABETH M. WARD
MICHAEL J. THUN
Measures of the Cancer Burden 226
Data Sources and Age Standardization 230
Temporal Trends 231
Demographic and Geographic Patterns 234
Issues in the Interpretation and Understanding of
Temporal Trends 238
Conclusion 240
5 12
Principles of Surgical Oncology 243
section 1 General Issues 243
STEVEN A. ROSENBERG
Historical Perspective 243
Anesthesia for Oncologic Surgery 244
Determination of Operative Risk 246
Roles for Surgery 249
Surgical Oncologist 251
section 2 Laparoscopic Surgery 253
ALBERT S. KO
ALAN T. LEFOR
Physiology of Laparoscopy 253
Port Site Metastases 255
Laparoscopy in the Diagnosis of Malignancy 257
Laparoscopy in the Staging of Malignancy 258
Laparoscopy in the Treatment of Malignancy 263
Laparoscopy in the Palliation of Malignancy 265
Conclusion 265
13
Principles of Radiation Oncology 267
PHILIP P. CONNELL
MARY K. MARTEL
SAMUEL HELLMAN
Biologic Aspects of Radiation Oncology 267
Physical Aspects of Radiation Oncology 276
Clinical Aspects of Radiation Oncology 285
VVWi Contents
14
Principles of Medical Oncology. 29£
EDWARD CHU
VINCENT T. DEVITA, JR.
Historical Perspective 295
Clinical Application of Chemotherapy 296
Clinical End Points in Evaluating Response to Chemotherapy 297
Cancer Cell Kinetics and Response to Chemotherapy 298
Principles Governing the Use of Chemotherapy 298
Concept of Dose Intensity 300
Apoptosis, Cell Cycle Control, and Resistance to Chemotherapy 301
15
Pharmacology of Cancer Chemotherapy 307
section 1 Drug Development 307
EDWARD CHU
Drug Discovery 307
Combinatorial Chemistry 309
Drug Screening 311
Molecularly Targeted Screening 312
Preclinical Pharmacology 313
Formulation Studies 314
Preclinical Toxicology 315
Clinical Development 315
Conclusion 316
section 2 Pharmacokinetics 317
CHRIS H. TAKIMOTO
Introduction 317
Pharmacokinetic Concepts 319
Pharmacodynamic Concepts 323
Special Topics in Pharmacokinetics and Pharmacodynamics 324
Pharmacokinetics and Pharmacodynamics in Oncology Drug Development 325
Conclusion 326
section 3 Pharmacogenomics 327
HOWARD L. MCLEOD
BOON CHER GOH
Pharmacogenomics of Chemotherapy Drug Toxicity 327
Pharmacogenomics of Tumor Response 330
Conclusion 331
section 4 Alkylating Agents 332
O. MICHAEL COLVIN
HENRY S. FRIEDMAN
History of the Alkylating Agents 332
Contents xxxvii
Chemistry and Cytotoxicity of Alkylating Agents 332
Classes of Alkylating Agents and Their Properties 332
Mechanisms of Toxicity and Drug Resistance 338
Common Toxicities of Alkylating Agents 340
section 5 Cisplatin and Its Analogues 344
STEVEN W. JOHNSON
PETER J.O'DWYER
History 344
Platinum Chemistry 345
Novel Platinum Complexes 345
Mechanism of Action 347
Mechanisms of Resistance 349
Clinical Pharmacology 352
Formulation and Administration 354
r Toxicity 354
section 6 Antimetabolites 358
SHIVAANIKUMMAR
VANITA NORONHA
EDWARD CHU
Methotrexate 358
New Antifolates 361
section 7 Topoisomerase Interactive Agents 375
CHRIS H. TAKIMOTO
Mammalian Topoisomerases 375
Mechanism of Action of Topoisomerase Interactive Agents 377
Camptothecins 377
Epipodophyllotoxins 381
Anthracyclines and Related Compounds 384
Other Topoisomerase Interactive Agents 388
Secondary Malignancies and Topoisomerase Targeting Therapies 389
section 8 Antimicrotubule Agents 390
ERIC K. ROWINSKY
ANTHONY W. TOLCHER
Microtubules 390
Vinca Alkaloids 392
Taxanes 398
Estramustine Phosphate 407
Novel Compounds Targeting Microtubules 410
Novel Compounds Targeting Mitotic Motor Proteins 411
section 9 Miscellaneous Chemotherapeutic Agents 416
MEHMET SITKI COPUR
MICHAL G. ROSE
EDWARD CHU
L Asparaginase 416
\W\iii Contents
Bleomycin 427
Imatinib Mesylate 417
Gefitinib 418
Bortezomib 420
16
Pharmacology of Cancer Biotherapeutics 423
suction 1 Interferons 423
VERNON K. SONDAK
BRUCE G. REDMAN
Interferon Induction 423
Biologic Effects of Interferons 424
Clinical Toxicity of Interferon Administration 426
Potential Drug Interactions 427
Oncologic Applications of Interferons 427
Conclusion 429
section 2 Interleukin 2 431
JAMES W. MIER
MICHAEL B. ATKINS
Isolation, Characterization, and Cloning of Interleukin 2 431
Interleukin 2 Receptor 431
Interleukin 2 Activated Signaling Pathways 431
In Vitro Effects of Interleukin 2 432
Preclinical Studies with Interleukin 2 in Tumor Bearing Mice 432
Clinical Applications of Interleukin 2 432
Conclusion 437
section 3 Histone Deacetylase Inhibitors: New Targeted Anticancer Drugs 439
PAUL A. MARKS
VICTORIA M. RICHON
THOMAS A. MILLER
WM. KEVIN KELLY
Chromatin Structure 439
Histone Deacetylases and Histone Acetyl Transferases 439
Histone Acetyltransf erases and Histone Deacetylase Inhibitors and Human Cancers 439
Histone Deacetylase Inhibitors 441
Activity of Histone Deacetylase Inhibitors 441
Clinical Trials with Histone Deacetylase Inhibitors 443
Conclusion and Perspectives 444
section 4 Monoclonal Antibodies 445
JONATHAN D. CHENG
GREGORY PAUL ADAMS
MATTHEW K. ROBINSON
LOUIS M. WEINER
Immunoglobulin Structure 446
Contents \\\\\
Factors Regulating Antibody Based Tumor Targeting 447
Unconjugated Antibodies 448
Immunoconjugates 451
Pretargeted Antibody Conjugates 453
Unconjugated Antibodies with Clinical Activity in
Solid Tumors 453
Conclusion 454
17
Pharmacology of Endocrine Manipulation 457
MATTHEW P. GOETZ
CHARLES ERLICHMAN
CHARLES L. LOPRINZI
Selective Estrogen Receptor Modulators 457
Medroxyprogesterone and Megestrol 461
Aromatase Inhibitors 462
Gonadotropin Releasing Hormone Analogues 464
Antiandrogens 464
Fluoxymesterone 465
Diethylstilbestrol and Estradiol (Estrace) 465
Octreotide 466
18
Design and Analysis of Clinical Trials 471
RICHARD M. SIMON
Phase I Clinical Trials 471
Phase II Clinical Trials 473
Design of Phase III Clinical Trials 478
Analysis of Phase III Clinical Trials 483
PARTlS
PRACTICE OF ONCOLOGY
19
Cancer Prevention: Preventing Tobacco Related Cancers 493
HOWARD K. KOH
ALAN C. GELLER
Tobacco and Nicotine Addiction 493
Health Effects 493
Smoking Rates and Trends 494
Adults 494
Children, Adolescents, and College Students 495
\l Contents
Cigarette Product Modification 495
Spit Tobacco 496
Cigars 496
Environmental Tobacco Smoke 496
Tobacco Industry Advertising Strategies 497
Strategies for Tobacco Control 498
Individual Approaches 498
Clinician's Role 498
Nicotine Replacement Therapy 499
Special Populations 500
National Action Plan for Tobacco Cessation 500
Tobacco Restrictions at the Policy Level 500
Tobacco Taxes that Fund Dedicated, Comprehensive Statewide Tobacco Control Programs 500
Mass Media and Counter Advertising 501
Tobacco Litigation, Tobacco Settlement, and International Treaties 502
Proposed U.S. Food and Drug Administration Regulations 502
Conclusion 503
20
Cancer Prevention: Diet and Chemopreventive Agents 507
skction 1 Dietary Fat 507
WALTER C. WILLETT
Fat and Breast Cancer 508
Fat and Colon Cancer 509
Fat and Prostate Cancer 510
Fat and Other Cancers 511
Conclusion 511
sectios 2 Dietary Fiber 514
KARIN B. MICHELS
Diet and Cancer Etiology 514
Properties of Dietary Fiber 514
Observational Studies and Clinical Trials 514
Types of Dietary Fiber 515
Calculation of Fiber Intake 515
Dietary Fiber and Colorectal Cancer 515
Fiber Intake and Colorectal Adenomas 516
Fiber Intake and Breast Cancer 516
Dietary Fiber and Stomach Cancer 516
Timing of Diet 517
Conclusion 517
si;cti )\ 3 Fruit and Vegetable Consumption 518
KARIN B. MICHELS
Fruits and Vegetables 518
Diet Assessment Instruments 518
Confounding 518
Fruit and Vegetable Consumption and Colorectal Cancer 518
C.onlnils \li
Fruit and Vegetable Consumption and Stomach Cancer 518
Fruit and Vegetable Consumption and Breast Cancer 579
Fruit and Vegetable Consumption and Lung Cancer 579
Micronutrient Components of Fruits and Vegetables and Cancer 579
Conclusion 520
section 4 Retinoids, Carotenoids, and Micronutricnts 521
SUSAN T. MAYNE
SCOTT M. LIPPMAN
Historical Perspective 527
Retinoid Biology and Pharmacology 522
Carotenoid Biology and Actions 522
Clinical Trials 523
Translational and Intermediate End Point Studies in Retinoid Chemoprevention 532
Other Retinoids and Carotenoids 533
Conclusion 533
section 5 Dietary Carcinogens 536
PETER GREENWALD
Naturally Occurring Dietary Carcinogens 536
Products of Food Preparation and Processing 538
Synthetic Carcinogens in the Diet 540
Future Research Needs 540
section G Cyclooxygenasc Inhibitors 541
MICHAEL J. THUN
S. JANE HENLEY
Pharmacology of Nonsteroidal Antiinflammatory Drugs 547
Toxicity of Nonsteroidal Antiinflammatory Drugs 542
History of the Inflammation Hypothesis 542
Nonsteroidal Antiinflammatory Drugs in Relation to Other Cancers 543
Mechanisms of Cancer Inhibition 544
Molecular Target(s) 546
Ongoing Randomized Clinical Trials 546
Implications for Research and Clinical Practice 546
Conclusion 548
section 7 Physical Activity and Body Weight 549
GRAHAM A. COLDITZ
KATHLEEN YAUS WOLIN
Physical Activity 549
Obesity 552
Conclusion 553
21
Cancer Prevention: Role of Surgery in Cancer Prevention 555
RICHARD M. SHERRY
Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid Carcinoma 555
vlii Contents
Barrett's Esophagus and Esophageal Cancer 556
Hereditary Diffuse Gastric Cancer 558
Colorectal Cancer 558
Breast Cancer 561
Ovarian Cancer 563
Testicular Cancer and Cryptorchidism 564
22
Cancer Screening 567
BARBARA K. RIMER
JOELLEN M. SCHILDKRAUT
ROBERT A. HIATT
What Is Cancer Screening? 567
Evaluation of a Screening Test 568
Breast Cancer Screening 569
Cervical Cancer Screening 572
Colorectal Cancer Screening 573
Skin Cancer Screening 574
Prostate Cancer Screening 574
Lung Cancer Screening 576
Adherence to Cancer Screening 577
Future of Screening 577
23
Advanced Molecular Diagnostics 581
JOSE C. COSTA
PAUL M. LIZARDI
Present Impact of Novel Technologies on Clinical Practice 582
Charting the Future 584
Conclusion 586
24
Advanced Imaging Methods 589
SEcrios 1 Functional and Metabolic Imaging 589
HEDVIG HRICAK
OGUZ AKIN
MICHELLE S. BRADBURY
LAURA LIBERMAN
LAWRENCE H. SCHWARTZ
STEVEN M. LARSON
Imaging Modalities 589
Therapeutic Response Assessment 594
Brain and Head/Neck Cancers 595
Lung Cancer 597
Lymphoma 600
Breast Cancer 601
Hepatobiliary Cancer 604
Colorectal Cancer 605
Contents xliii
Gynecologic Cancer 607
Endometrial Cancer 607
Cervical Cancer 608
Ovarian Cancer 609
Prostate Cancer 610
Molecular Imaging in Oncology 611
section 2 Interventional Radiology 617
ANNE M. COVEY
KAREN T. BROWN
Percutaneous Biopsy 617
Central Venous Access 619
Gastrointestinal Procedures 629
Genitourinary Procedures 620
Biliary Procedures 623
Chest Interventions 626
Inferior Vena Cava Filters 629
Ascites 630
Abscess Drainage 631
Embolotherapy for Hepatic Neoplasms 631
Tumor Ablation 632
Emerging Therapies and Future Directions 634
25
Cancer Diagnosis: Endoscopy 637
section 1 Gastrointestinal Endoscopy 637
IRVING WAXMAN
Upper Endoscopy 637
Colonoscopy 640
Endoscopic Ultrasonography 641
Small Bowel Endoscopy and Capsule Endoscopy 641
Endoscopic Retrograde Cholangiopancreatography 642
section 2 Respiratory Tract 643
DAO M. NGUYEN
RONALD M. SUMMERS
STEVEN E. FINKELSTEIN
Bronchoscopy 643
Virtual Bronchoscopy 645
Cervical Mediastinoscopy and Anterior Mediastinotomy 647
Video Assisted Thoracoscopy 648
26
Cancer of the Head and Neck 653
section 1 Molecular Biology of Head and Neck Tumors 653
DAVID SIDRANSKY
Genetic Susceptibility 653
xliv Contents
Cytogenetic Alterations 653
Protooncogenes 654
Suppressive Growth Regulation 655
Tumor Suppressor Genes 655
Field Cancerization 657
Molecular Epidemiology 658
Human Papillomavirus 658
Diagnostics 658
section 2 Treatment of Head and Neck Cancers 662
WILLIAM M. MENDENHALL
CHARLES E. RIGGS, JR.
NICHOLAS J. CASSISI
Epidemiology of Head and Neck Cancer 662
Anatomy 662
Pathology 662
Natural History and Patterns of Spread of Squamous
Cell Carcinoma 663
Diagnostic Evaluation 665
Staging 665
General Principles for Selection of Treatment 665
Management 666
section 3 Rehabilitation after Treatment for Head and Neck Cancer 732
MICHAEL A. CRARY
GISELLE D. CARNABY (MANN)
General Functional Consequences of Treatment for Head and
Neck Cancer 732
Tracheostomy Issues 734
Radiation Therapy Impact on Speech, Voice, and Swallowing
Functions 735
Evaluation of Speech, Voice, and Swallowing after Head and Neck
Cancer Treatment 736
Rehabilitation of Posttreatment Functional Limitations 738
Conclusion 742
27
Cancer of the Lung 745
section 1 Molecular Biology of Lung Cancer 745
YOSHITAKA SEKIDO
KWUN M. FONG
JOHN D. MINNA
Genetic and Epigenetic Alterations in Lung Cancers 745
Protooncogenes and Growth Stimulation 746
Tumor Suppressor Genes and Growth Suppression 748
Other Biologic Abnormalities for Lung Cancer Development 749
Molecular Tools in the Lung Cancer Clinic 751
C.onli'nls vlv
section 2 Non Small Cell Lung Cancer 753
DAVID S. SCHRUMP
NASSER K. ALTORKI
CLAUDIA L. HENSCHKE
DARRYL CARTER
ANDREW T. TURRISI
MARTIN E. GUTIERREZ
Incidence 753
Etiology 753
Pathology 757
Modes of Metastasis 761
Clinical Manifestations 762
Staging and Diagnosis 763
Methods to Establish Tissue Diagnosis 766
Lung Cancer Screening 768
Chemoprevention 770
Overview of Invasive Lung Cancer Management: Treatment Modalities 770
Specifics of Lung Cancer Management 777
section 3 Small Cell Lung Cancer 810
JOHN R. MURREN
ANDREW T. TURRISI
HARVEY I. PASS
Epidemiology and Etiology 810
Pathology 810
Clinical Presentation 811
Staging Evaluation and Prognostic Factors 812
Treatment 815
Combination Chemotherapy 816
Duration of Chemotherapy 818
Approach to Patients with Limited Disease 819
Role of Radiotherapy in Limited Disease 820
Role of Surgery in Limited Disease 823
Approach to Patients with Extensive Disease 826
Strategies to Optimize Chemotherapy Response 827
Hematopoietic Growth Factors 830
Management of Small Cell Lung Cancer in the Elderly and Infirm 832
Biologic Response Modifiers and Other Treatments 833
Treatment at Relapse 834
Treatment Outcome and Long Term Survival 835
Extrapulmonary Small Cell Carcinoma 836
28
Neoplasms of the Mediastinum 845
ROBERT B. CAMERON
PATRICK J. LOEHRER, SR.
CHARLES R. THOMAS, JR.
Anatomy 845
Incidence and Pathology 845
Diagnostic Considerations 846
\hi Contents
Thymic Neoplasms 848
Germ Cell Tumors 852
Mesenchymal Tumors 855
Neurogenic Tumors 855
Primary Cardiac Malignancies 858
29
Cancers of the Gastrointestinal Tract 861
sm:tio\ 1 Cancer of the Esophagus 861
MITCHELL C. POSNER
ARLENE A. FORASTIERE
BRUCE D. MINSKY
Epidemiology 861
Etiologic Factors and Predisposing Conditions 862
Applied Anatomy and Histology 865
Molecular Biology 867
Natural History and Patterns of Failure 869
Clinical Presentation 869
Diagnostic Studies and Pretreatment Staging 870
Pathologic Staging 871
Treatment 872
Stage Directed Treatment Recommendations 901
sh:cTio\ 2 Cancer of the Stomach 909
PETER W. T. PISTERS
DAVID P. KELSEN
STEVEN M. POWELL
JOEL E. TEPPER
Epidemiology and Etiology 909
Molecular Biology 912
Pathology and Tumor Biology 914
Clinical Presentation and Pretreatment Evaluation 915
Staging, Classification, and Prognosis 917
Treatment of Localized Disease 921
Treatment of Advanced Disease (Stage IV) 934
shctk)\ 3 Cancer of the Pancreas 945
CHARLES J. YEO
THERESA PLUTH YEO
RALPH H. HRUBAN
SCOTT E. KERN
CHRISTINE A. IACOBUZIO DONOHUE
ANIRBAN MAITRA
MICHAEL GOGGINS
MARCIA I. CANTO
WELLS MESSERSMITH
ROSS A. ABRAMS
DANIEL A. LAHERU
MANUEL HIDALGO
ELIZABETH M. JAFFEE
Epidemiology and Risk Factors 945
Contents xlvii
Pathology 947
Molecular Genetics 950
Gene Expression Profiling and Beyond 952
Screening and Early Detection 953
Clinicopathologic Staging 955
Clinical Presentation and Evaluation 957
Treatment of Potentially Resectable Disease 960
Treatment of Locally Advanced Disease 969
Treatment of Metastatic and Recurrent Disease 973
Immunotherapy 982
section 4 Cancer of the Liver 986
DAVID L. BARTLETT
BRIAN I. CARR
J. WALLIS MARSH
Epidemiology 987
Etiologic Factors 988
Pathology 992
Clinical Features 991
Staging 993
Clinical Evaluation 993
Screening of High Risk Populations 995
Clinical Management 996
Treatment of Other Primary Liver Tumors 2003
Summary: Practical Guide to the Management of Patients
with Hepatocellular Carcinoma 2004
section 5 Cancer of the Biliary Tree 1009
DAVID L. BARTLETT
RAMESH K. RAMANATHAN
MELVIN DEUTSCH
Cholangiocarcinomas 2009
Tumors of the Gallbladder 2022
New Advances for Treatment of Biliary Tract Cancers 2032
section 6 Cancer of the Small Intestine 1035
HERBERT J. ZEH III
Incidence 2036
Pathogenetic Mechanisms in Small Intestinal Carcinogenesis 2036
Genetic and Environmental Factors That Predispose to Malignancy
Arising in the Small Intestine 2037
Presentation and Diagnosis of Cancers Arising in the Small Intestine 1038
Adenocarcinoma Arising in the Small Intestine 2040
Carcinoid Tumors Arising in the Small Intestine 2042
Lymphoma Arising in the Small Intestine 2044
Mesenchymal Tumors Arising in the Small Intestine 2046
section 7 Gastrointestinal Stromal Tumors 1050
GEORGE D. DEMETRI
Histopathologic Features and Histogenesis 2050
Ylviii Contents
Clinical Considerations 1052
Treatment Options and Management Decisions in the Era of Molecularly Targeted Therapies f
Gastrointestinal Stromal Tumor 2054
Special Considerations in Gastrointestinal Stromal Tumor 1058
New Challenges and Alternative Approaches 1059
section 8 Cancer of the Colon 1061
STEVEN K. LIBUTTI
LEONARD B. SALTZ
ANIL K. RUSTGI
JOEL E. TEPPER
Epidemiology 1061
Etiology: Genetic and Environmental Risk Factors 1062
Biology of Colorectal Cancer: Clinical and Molecular
Genetic Risk Factors 1063
Anatomy of the Colon 1065
Diagnosis 2067
Screening 1068
Staging and Prognosis 1068
Approaches to Surgical Resection of Colon Cancer 1076
Polyps and Stage I Colon Cancer 1080
Stage II and Stage HI Colon Cancer 1080
Surgical Management of Stage IV Disease 2089
Management of Unresectable Metastatic Disease 1089
Management of Synchronous Primary and Metastatic Disease 2202
Unusual Colorectal Tumors 2 2 02
section 9 Cancer of the Rectum 1110
STEVEN K. LIBUTTI
JOEL E. TEPPER
LEONARD B. SALTZ
ANIL K. RUSTGI
Anatomy 2220
Staging 2222
Surgery 2223
Stage I 2223
Combined Modality Therapy (Stages II and III) 2226
Concurrent Chemotherapy 2229
Management of Unresectable Primary and Locally Advanced
Disease (T4) 2220
Radiation Therapy Technique 2222
Radiation Fields 2222
section 10 Cancer of the Anal Region 1125
BERNARD J. CUMMINGS
JAFFERA.AJANI
CAROL J. SWALLOW
Anatomy 2225
Pathology 2226
Epidemiology 2226
Risk Factors and Etiology 2226
Contents \\\\
Natural History 2227
or Staging 1128
Prognostic Factors 7229
Anal Canal Squamous Cancers 1129
Adenocarcinomas 1135
Small Cell Cancers 1135
Perianal Cancers 1135
Special Considerations: Patients with Human Immunodeficiency Virus Infection/
Acquired Immunodeficiency Syndrome 1136
30
Cancers of the Genitourinary System 1139
section 1 Cancer of the Kidney 1139
W. MARSTON LINEHAN
SUSAN E. BATES
JAMES C. YANG
Histologic Types of Renal Carcinoma 1139
Localized Renal Carcinoma 1149
Metastatic Renal Carcinoma 2252
section 2 Cancer of the Bladder, Ureter, and Renal Pelvis 1168
WILLIAM U. SHIPLEY
DONALD S. KAUFMAN
W. SCOTT MCDOUGAL
DOUGLAS M. DAHL
M. DROR MICHAELSON
ANTHONY L. ZIETMAN
Epidemiology 2265
Screening and Early Detection 1169
Pathology 2269
Molecular Tumor Markers 1170
Cancer of the Bladder 2 2 72
Cancers of the Ureter and Renal Pelvis 2285
section 3 Cancer of the Prostate 1192
HOWARD I. SCHER
STEVEN A. LEIBEL
ZVI FUKS
CARLOS CORDON CARDO
PETER T. SCARDINO
States and State Transitions 2292
Biologic Characterization and Pathology 2 295
Initial Urologic Evaluation: No Cancer Diagnosis 2203
Localized Disease 2209
Radiation Therapy 2222
Expectant Management 2230
Systemic Therapies 2232
Clinical Metastases: Castrate 2242
Conclusion 2250
section 4 Cancer of the Urethra and Penis 1260
SANJAY RAZDAN
LEONARD G. GOMELLA
Cancer of the Male Urethra 1260
Carcinoma of the Female Urethra 1261
Cancer of the Penis 1262
31
Cancer of the Testis 1269
GEORGE J. BOSL
DEAN F. BAJORIN
JOEL SHEINFELD
ROBERT J.MOTZER
R. S. K. CHAGANTI
Background: Incidence 1269
Epidemiology 1269
Initial Presentation and Management 1270
Histology 1270
Staging 1274
Management of Clinical Stage I Disease 1277
Management of Clinical Stage II Disease (Low Tumor Burden) 1281
Management of Stage II and Stage III Disease (High Tumor Burden) 1282
Management of Relapse after Chemotherapy and Refractory Disease 1286
Treatment Sequelae 1287
Midline Tumors of Uncertain Histogenesis 1289
Other Testicular Tumors 1289
32
Gynecologic Cancers 1295
section 1 Cancer of the Cervix, Vagina, and Vulva 1295
PATRICIA J. EIFEL
JONATHAN S. BEREK
MAURIE A. MARKMAN
Carcinoma of the Cervix 1295
Carcinoma of the Vagina 1320
Carcinoma of the Vulva 1326
section 2 Cancers of the Uterine Body 1341
THOMAS W. BURKE
ARNOJ. MUNDT
FRANCO M. MUGGIA
Endometrial Carcinoma 1341
Uterine Sarcomas 2354
section 3 Gestational Trophoblastic Diseases 1360
FRANCO M. MUGGIA
THOMAS W. BURKE
WILLIAM SMALL, JR
Epidemiology 1360
Pathology and Biology 7367
Clinical Diagnosis and Human Chorionic Gonadotropin 7367
Choriocarcinoma 7362
suction 4 Ovarian Cancer, Peritoneal Carcinoma, and Fallopian l\ibe Carcinoma 1364
BETH Y. KARLAN
MAURIE A. MARKMAN
PATRICIA J. EIFEL
Ovarian Cancer 7364
Borderline Tumors 1388
Primary Peritoneal Carcinoma 7389
Germ Cell Tumors of the Ovary 7390
Sex Cord Stromal Tumors 7392
Fallopian Tube Cancer 1393
33
Cancer of the Breast 1399
section 1 Molecular Biology of Breast Cancer 1399
ROBERT B. DICKSON
RICHARD G. PESTELL
MARC E. LIPPMAN
Genetics 7399
Steroid and Growth Factor Pathways of Cellular Regulation 7402
Cell Cycle and Cell Death 7408
Process of Malignant Progression 7470
Implications of Molecular Biology for Tumor Prevention, Early Detection,
Prognosis, and Response to Therapy 7477
section 2 Malignant Tumors of the Breast 1415
WILLIAM C. WOOD
HYMAN B. MUSS
LAWRENCE J. SOLIN
OLUFUNMILAYO I. OLOPADE
Risk Factors for Breast Cancer 7475
Diagnosis and Biopsy 1418
Pathologic Classification of Tumor Types 7420
Staging of Breast Cancer 1421
Prognostic and Predictive Factors 7423
Advising the Woman at High Risk for Breast Cancer 7427
Ductal Carcinoma In Situ 1429
Lobular Carcinoma In Situ 1434
Paget's Disease 7434
Early Stage Breast Cancer 7435
Locally Advanced and Inflammatory Breast Cancer 7450
Metastatic Breast Cancer 7453
Breast Cancer and Pregnancy 7462
Bilateral Breast Cancer 7464
Male Breast Cancer 7465
Nonepithelial Neoplasms 7465
lii Contents
Lymphoma of the Breast 1466
Axillary Lymph Node Presentation 1466
Local and Regional Recurrence 1467
Breast Cancer in the Elderly 1469
section 3 Rehabilitation after Treatment for Cancer of the Breast 1478
JEANNE A. PETREK
JOSEPH J. DISA
Delayed versus Immediate Reconstruction 1478
Prosthetic Reconstruction 1478
Autologous Tissue Reconstruction 1479
Postmastectomy after Breast Irradiation 1481
Skin Sparing Mastectomy with Immediate Reconstruction 1481
Lymphedema 1483
34
Cancer of the Endocrine System 1489
section 1 Molecular Biology of Endocrine Tumors 1489
TERRY C. LAIRMORE
JEFFREY F. MOLEY
Multiple Endocrine Neoplasia Syndromes 1489
Molecular Pathogenesis of Sporadic Thyroid Neoplasms 1495
Genetic Abnormalities in Parathyroid Neoplasms 2497
Other Genetic Loci Implicated in Familial Hypercalcemic Syndromes 1498
Parathyroid Carcinoma 1499
Genetic Abnormalities in Adrenal Neoplasms 1499
Conclusion 1500
section 2 Thyroid Tumors 1502
TOBIAS CARLING
ROBERT UDELSMAN
Thyroid Tumor Classification and Staging Systems 1502
Epidemiology and Demographics 1503
Etiology and Risk Factors 1503
Evaluation of the Thyroid Nodule 1506
Well Differentiated Thyroid Carcinoma 1508
Treatment of Well and Intermediately Differentiated
Thyroid Carcinoma 1510
Poorly Differentiated Thyroid Carcinoma 1514
Medullary Thyroid Carcinoma 1515
Thyroid Lymphoma 1517
Metastatic Disease of the Thyroid 1518
Thyroid Carcinoma in Children 1518
section 3 Parathyroid Tumors 1521
DOUGLAS L. FRAKER
Primary Hyperparathyroidism 1521
Pathology 1521
Molecular Genetics 2522
Epidemiology 7522
Clinical Presentation 7524
Natural History 7524
Differential Diagnosis 7525
Treatment 7525
Outcome 7526
section 4 Adrenal Tumors 1528
JEFFREY A. NORTON
Pathology of the Adrenal Cortex 1528
Clinical Presentations of Adrenal Cortical
Neoplasms 7529
Treatment of Adrenal Cortical Neoplasms 7533
Pheochromocytoma 7535
section 5 Pancreatic Endocrine Tumors 1540
H. RICHARD ALEXANDER, JR
ROBERT T. JENSEN
Pathogenesis, Pathology, Tumor Biology 7547
Clinical Presentation and Diagnosis 7543
Imaging and Localization of Pancreatic
Endocrine Tumors 7547
Treatment of Resectable Disease 7548
Treatment of Metastatic Disease 7555
suction 6 Carcinoid Tumors and the Carcinoid Syndrome 1559
ROBERT T. JENSEN
GERARD M. DOHERTY
Pathology and Tumor Histology 7559
Molecular Pathogenesis 7562
Clinical Features 7562
Carcinoid Syndrome 1563
Treatment of the Carcinoid Tumor 7577
section 7 Multiple Endocrine Neoplasias 1575
GERARD M. DOHERTY
ROBERT T. JENSEN
Multiple Endocrine Neoplasia Type 1 7575
Familial Medullary Thyroid Carcinoma and Multiple Endocrine Neoplasia
Types 2A and 2B 1578
35
Sarcomas of the Soft Tissues and Bone 1581
section 1 Soft Tissue Sarcoma 1581
MURRAY F. BRENNAN
SAMUEL SINGER
ROBERT G. MAKI
BRIAN O'SULLIVAN
Incidence 1587
liv Contents
Etiology and Genetics 1581
Distribution 1584
Pathologic Classification 1584
Grading of Sarcoma 1587
Differential Diagnosis 1588
Clinicopathologic Features of Specific Types of Benign and Malignant
Soft Tissue Tumors 1589
Clinical Presentation 1597
Differential Diagnosis 1597
Management of Extremity and Superficial Truncal Soft Tissue
Sarcoma 1602
Radiation Therapy 1603
Adjuvant Brachytherapy 1608
Special Considerations 1609
Definitive Radiation 1610
Adjuvant Chemotherapy 1611
Preoperative Chemotherapy 1616
Intraarterial Chemotherapy 1617
Hyperthermia and Limb Perfusion 1617
Special Features of the Management of Sarcomas of
Nonextremity Sites 1618
Serious Complications of Primary Treatment 1620
Prognostic Factors 1622
Quality of Life and Functional Outcome 1623
Treatment of Local Recurrence 1623
Management of Advanced Disease 1624
Resection of Metastatic Disease 1624
Systemic Therapy for Advanced Disease 1624
Response by Histologic Subtype and Site 1629
Recommendations for Patients with Advanced
Disease 1631
Future Directions 2632
section 2 Sarcomas of Bone 1638
MARTIN M. MALAWER
LEE J. HELMAN
BRIAN O'SULLIVAN
Classification and Types of Bone Tumor 1638
Radiographic Evaluation and Diagnosis 2639
Natural History 2640
Staging Bone Tumors 2642
Preoperative Evaluation 2642
Biopsy Technique and Timing 2644
Restaging after Induction (Preoperative) Chemotherapy 2645
Surgical Management of Skeletal Tumors 2646
Principles and Techniques of Limb Sparing Surgery 2647
Limb Sparing Surgery and Perioperative Pain Management 1648
Amputations 1652
Cryosurgery 2652
Chemotherapy for Bone Sarcomas 2652
Radiotherapy for Bone Tumors 2658
Malignant Bone Tumors 2 660
Conlnit.s Iv
36
Benign and Malignant Mesothelioma 1687
HARVEY I. PASS
NICHOLAS J. VOGELZANG
STEPHEN M. HAHN
MICHELE CARBONE
Mechanism of Asbestos Induced Oncogenesis 1687
Mechanism of Asbestos Pathogenicity 1688
Overview of Molecular Mechanisms in Mesothelioma 1688
Simian Virus 40 1690
Radiation and Mesothelioma 1690
Genetic Predisposition to Mesothelioma 1690
Pathology of Mesothelioma 1691
Solitary Fibrous Tumors of Pleura 1693
Clinical Presentation of Malignant Pleural Mesothelioma 1693
Diagnostic Approach 1698
Natural History 1699
Prognostic Indicators 1699
Staging 1700
Treatment 1700
Malignant Peritoneal Mesothelioma 1710
Malignant Mesothelioma of the Tunica Vaginalis Testis 1712
Malignant Mesothelioma of the Pericardium 1712
37
Cancer of the Skin 1717
SUMAIRA Z. AASI
DAVID J.LEFFELL
Diagnosis 2727
General Approach to Management of Skin Cancer 1718
Precancerous Lesions 1723
Carcinoma Metastatic to Skin 2 742
Conclusion 2742
38
Melanoma 1745
suction 1 Molecular Biology of Cutaneous Melanoma 1745
ZHAO JUN LIU
MEENHARD HERLYN
Etiology of Melanoma 2745
Genetics of Melanoma 2746
Biologic Basis of Melanoma Development and Progression 2 749
section 2 Cutaneous Melanoma 1754
CHARLES M. BALCH
MICHAEL B. ATKINS
ARTHUR J. SOBER
Epidemiology 2754
Ivi Contents
Anatomic Distribution 1755
Risk Factors 1756
Prevention and Screening 2757
Diagnosis of Melanoma 1759
Prognostic Factors 1760
New Staging System for Melanoma 1765
Biopsy 1769
Surgical Treatment of Primary Melanoma (Stages I to III) 1769
Local Recurrences 1774
Management of Regional Nodes—Lymphadenectomy
(Stage III) 1774
Radiotherapy for Regional Metastases (Stage III) 1778
Regional Relapses 1779
Adjuvant Systemic Therapy (Stages II and III) 1780
Follow Up of Melanoma Patients (Stages I to III) 1786
Diagnosis of Stage IV Melanoma 1786
Surgery and Irradiation for Distant Metastases (Stage IV) 1787
Systemic Treatment of Stage IV Melanoma 1792
section 3 Intraocular Melanoma 1809
ROBERT B. AVERY
MINESH P. MEHTA
RICHARD M. AUCHTER
DANIEL M. ALBERT
Epidemiology 1809
Mortality 1810
Natural History 1810
Etiology and Pathogenesis 1811
Histopathology 1812
Diagnosis 1813
Prognostic Assessment 1815
Therapeutic Approaches 1816
Radiation Therapy 1817
Management 1823
Future Directions 1824
39
Neoplasms of the Central Nervous System 1827
skctio* 1 Molecular Biology of Central Nervous System Neoplasms 1827
DAVID N. LOUIS
WEBSTER K. CAVENEE
Diffuse, Fibrillary Astrocytomas 1827
Other Gliomas 2 £29
Medulloblastomas 1831
Meningiomas 1831
Peripheral Nerve Tumors 1832
Miscellaneous Tumors 1832
Neurologic Tumor Syndromes 1832
Conclusion 1833
Contents I\H
section 2 Neoplasms of the Central Nervous System 1834
HOWARD A. FINE
FRED G. BARKER II
JAMES M. MARKERT
JAY S. LOEFFLER
General Considerations 1834
Anatomic and Clinical Considerations 1836
Neurodiagnostic Tests 1838
Surgery 1841
Radiation Therapy 1843
Chemotherapy 1845
Cerebral Astrocytomas 2847
Brainstem Gliomas 1854
Cerebellar Astrocytomas 1856
Optic, Chiasmal, and Hypothalamic
Gliomas 1856
Oligodendrogliomas 1858
Ependymomas 1860
Meningiomas 1862
Primitive Neuroepithelial Tumors 1865
Medulloblastomas 1865
Pineal Region Tumors 1869
Pituitary Adenomas 1871
Craniopharyngiomas 1873
Acoustic Neuromas (Vestibular Schwannomas) 7874
Glomus Jugulare Tumors 1875
Chordomas and Chondrosarcomas 1876
Hemangioblastomas 1877
Choroid Plexus Papillomas and
Carcinomas 1879
Spinal Axis Tumors 1880
40
Cancers of Childhood 1889
section 1 Molecular Biology of Childhood Cancers 1889
LEE J. HELMAN
DAVID MALKIN
Tumor Suppressor Genes 1890
Retinoblastoma: The Paradigm 1890
Wilms' Tumor: Three Distinct Loci 1891
Neurofibromatoses 1892
Neuroblastoma 1892
Ewing's Sarcoma Family of Tumors 1893
Rhabdomyosarcoma 1893
Hereditary Syndromes Associated with Tumors of
Childhood 1894
Predictive Testing for Germline Mutations and Childhood
Cancers 1895
Molecular Therapeutics 1895
lviii Contents
sKcno\ 2 Solid Tumors of Childhood 1898
DAVID H. EBB
DANIEL M. GREEN
ROBERT C. SHAMBERGER
NANCY J. TARBELL
Epidemiology 1898
Management of Childhood Cancer 1898
Wilms' Tumor 1898
Favorable Histology Wilms' Tumor 1903
Neuroblastoma 1904
Retinoblastoma 1909
Advanced Unilateral Disease 1911
Limited Unilateral or Limited Bilateral
Disease 1911
Bilateral Disease 1911
Chemotherapy 1912
Rhabdomyosarcoma 1912
Ewing's Sarcoma and Peripheral Primitive Neuroectodermal
Tumor 1919
Primary Hepatic Tumors 1923
Germ Cell Tumors 1926
Clinical Presentation and Treatment by Anatomic
Site 1928
41
Lymphomas 1939
section 1 Leukemias and Lymphomas of Childhood 1939
HOWARD J. WEINSTEIN
NANCY J. TARBELL
Leukemias 1939
Non Hodgkin's Lymphoma 1948
Hodgkin's Disease 1953
section 2 Non Hodgkin's Lymphomas 1957
RICHARD I. FISHER
PETER M. MAUCH
NANCY LEE HARRIS
JONATHAN W. FRIEDBERG
Epidemiology 1957
Etiology 1958
Biologic Background for Classification of Lymphoid
Neoplasms 1959
Principles of the Revised European American Classification of Lymphoid Neoplasms/
World Health Organization Classification of Lymphoid
Neoplasms 1967
Principles of Management of Non Hodgkin's
Lymphoma 2969
Specific Disease Entities 1971
Special Clinical Situations 1990
Contents H\
si ;ctio\ 3 Cutaneous T Cell Lymphomas 1998
LYNN D. WILSON
GLENN W. JONES
MICHAEL GIRARDI
RICHARD L. EDELSON
PETER W. HEALD
Pathobiology 1998
Epidemiology 1998
Etiology 1998
Clinical Presentation 1999
Approach to the Patient with Mycosis Fungoides 2000
Patient Evaluation 2002
Principles of Therapy 2003
Other Clinical Management Issues 2010
section 4 Primary Central Nervous System Lymphoma 2012
LISA M. DEANGELIS
JOACHIM YAHALOM
Clinical Features 2012
Diagnostic Tests 2013
Pathology 2013
Management and Therapy 2014
Immunologically Normal Patients 2015
Immunocompromised Patients 2079
suction 5 Hodgkin s Lymphoma 2020
VOLKER DIEHL
NANCY LEE HARRIS
PETER M. MAUCH
History 2020
Etiology and Epidemiology 2021
Biology and Cell of Origin 2021
Pathology 2026
Diagnosis and Staging 2032
Clinical Presentation 2034
Treatment Methods 2035
Choice of Treatment 2038
Special Cases 2059
Sequelae 2062
Quality of Life 2064
New Drugs for Treatment of Hodgkin's Lymphoma 2064
Immunotherapy 2065
Gene Therapy 2068
42
Acute Leukemias 2077
sectios i Molecular Biology of Acute Leukemias 2077
D. GARY GILLILAND
GLEN DAVID RAFFEL
Leukemic Stem Cell 2077
l\ Contents
Recurring Chromosomal Abnormalities in Acute Leukemia 2078
Deletions and Numeric Abnormalities in Acute Leukemias 2083
Chromosomal Translocations That Result in Overexpression of
Otherwise Normal Genes 2084
Point Mutations in Acute Leukemia 2084
Mutational Complementation Groups in Acute Leukemias 2085
Conclusion 2086
suction 2 Management of Acute Leukemias 2088
DAVID A. SCHEINBERG
PETER G. MASLAK
MARK A. WEISS
Epidemiology and Etiology 2088
Biology of Acute Leukemias 2090
Diagnosis and Classification of Acute Leukemias 2091
Principles of Clinical Management of Acute Myelogenous
Leukemia 2098
Treatment of Newly Diagnosed Acute Myelogenous
Leukemia 2100
Induction 2100
Treatment of Relapsed Acute Myelogenous
Leukemia 2106
Conclusion 2115
43
Chronic Leukemias 2121
section 1 Chronic Myelogenous Leukemia 2121
BRIAN J. DRUKER
STEPHANIE J. LEE
Epidemiology 2121
Pathogenesis 2222
Diagnosis and Clinical Course 2223
Treatment of Chronic Phase Disease 2224
Advanced Phase Disease 2230
Future Directions 2232
suction 2 Chronic Lymphoid Leukemias 2133
SUSAN O'BRIEN
MICHAEL J. KEATING
Molecular Biology 2233
Immune Abnormalities 2235
Diagnosis 2135
Clinical Manifestations 2235
Treatment and Response Criteria 2138
Biologic Therapies 2240
Second Malignancies and Transformation 2242
Prolymphocytic Leukemia 2242
Large Granular Lymphocyte Leukemia 2242
Hairy Cell Leukemia 2242
Ciinlnils l\i
suction 3 Myelodysplastic Syndromes 2144
STEFAN FADERL
HAGOP M. KANTARJIAN
Incidence and Epidemiology 2144
Etiology 2144
Classification and Prognostic Factors 2145
Biology and Pathophysiology of Myelodysplastic Syndromes 2146
Clinical Manifestations 2148
Laboratory Features 2148
Differential Diagnosis 2148
Subtypes of Myelodysplastic Syndromes 2148
Therapy of Myelodysplastic Syndromes 2149
Conclusion 2153
44
Plasma Cell Neoplasms 2155
NIKHIL C. MUNSHI
KENNETH C. ANDERSON
History 2255
Epidemiology 2156
Etiology: Environmental Exposure 2156
Pathogenesis 2157
Clinical Manifestations 2163
Diagnosis 2165
Differential Diagnosis 2168
Prognostic Variables 2170
Treatment 2172
Waldenstrom's Macroglobulinemia 2181
45
Paraneoplastic Syndromes 2189
SUSANNE M. ARNOLD
FRANK S. LIEBERMAN
KENNETH A. FOON
Endocrinologic Manifestations of Cancer 2189
Hematologic Manifestations of Cancer 2193
Gastrointestinal Manifestations of Cancer 2196
Renal Manifestations of Nonrenal Cancer 2797
Cutaneous Manifestations of Cancer 2197
Neurologic Manifestations of Cancer 2200
Miscellaneous Paraneoplastic Syndromes 2207
46
Cancer of Unknown Primary Site 2213
F. ANTHONY GRECO
JOHN D. HAINSWORTH
Poorly Differentiated Neoplasms of Unknown Primary Site 2214
lvii Contents
Poorly Differentiated Carcinoma (with or without Features of Adenocarcinoma)
of Unknown Primary Site 2216
Neuroendocrine Carcinoma of Unknown Primary Site 2221
Adenocarcinoma of Unknown Primary Site 2222
Squamous Carcinoma of Unknown Primary Site 2225
Chemotherapy for Metastatic Carcinoma of Unknown Primary Site 2226
Special Issues in Carcinoma of Unknown Primary Site 2229
Conclusion 2232
47
Peritoneal Carcinomatosis 2237
JAMES F. PINGPANK, JR.
Pathophysiology 2237
Diagnostic Evaluation 2238
Histologic Subtypes 2238
Treatment 2242
48
Immunosuppression Related Malignancies 2247
section 1 AIDS RelatedMalignancies 2247
ROBERT YARCHOAN
RICHARD F. LITTLE
Kaposi's Sarcoma 2247
AIDS Associated Lymphomas 2253
Primary Central Nervous System Lymphoma in AIDS 2258
Hodgkin's Disease 2259
Anogenital Cancers in Human Immunodeficiency Virus
Infection 2259
Future Directions 2260
section 2 Transplantation Related Malignancies 2263
STANLEY R. RIDDELL
Immune Surveillance and Tumor Development 2263
Hematopoietic Stem Cell Transplant Recipients 2263
Organ Transplant Recipients 2267
49
Oncologic Emergencies 2273
sEcmn I Superior Vena Cava Syndrome 2273
JOACHIM YAHALOM
Anatomy and Pathophysiology 2273
Etiology and Natural History 2273
Diagnostic Procedures 2275
Management 2276
Caiiifiiis Iviii
Treatment 2277
Recommendations 2279
section 2 Increased Intracranial Pressure 2281
JOACHIM M. BAEHRING
Pathophysiologic Considerations 2281
Epidemiology and Pathogenesis 2281
Clinical Presentation 2282
Diagnosis 2284
Treatment 2286
section 3 Spinal Cord Compression 2287
JOACHIM M. BAEHRING
Epidemiology 2287
Pathophysiology 2287
Clinical Presentation 2289
Differential Diagnosis 2290
Diagnosis 2290
Treatment 2291
Prognosis 2291
Conclusion 2292
section 4 Metabolic Emergencies 2292
ANTONIO TITO FOJO
Tumor Lysis Syndrome 2292
Hyperuricemia 2294
Cancer and Hyponatremia 2295
Lactic Acidosis and Cancer 2296
Hypercalcemia and Cancer 2297
Cancer Related Hemolytic Uremic Syndrome 2299
section 5 Urologic Emergencies 2301
JONATHAN A. COLEMAN
MCCLELLAN M. WALTHER
Urinary Tract Infection 2301
Cystitis 2301
Bladder Hemorrhage 2304
Urinary Obstruction 2305
Priapism 2307
Paraphimosis 2307
50
Specialized Techniques in Cancer Management 2309
section 1 Vascular Access and Specialized Techniques of Drug Delivery 2309
JAMES F. PINGPANK, JR.
Catheter Types 2309
Catheter Selection 2312
Insertion Techniques 2312
Catheter Related Complications 2314
suction 2 Isolation Per fusion 2316
H. RICHARD ALEXANDER, JR.
Principles of Isolation Perfusion 2316
Results of Isolation Perfusion 2318
Current Status of Isolated Limb Perfusion 2319
Current Status of Isolated Hepatic Perfusion 2321
Status of Isolation Perfusion of Other Sites 2321
Variations of Isolation Perfusion Techniques 2321
Conclusion 2321
51
Treatment ofMetastatic Cancer 2323
section 1 Metastatic Brain Cancer 2323
DAVID A. LARSON
JAMES L. RUBENSTEIN
MICHAEL W. MCDERMOTT
Brain Metastases 2323
Carcinomatous Meningitis 2333
section 2 Metastatic Cancer to the Lung 2337
MICHAEL R. JOHNSTON
MARC DE PERROT
Biology 2337
Diagnosis 2337
Treatment 2339
Results 2346
section 3 Metastatic Cancer to the Liver 2352
H. RICHARD ALEXANDER, JR.
NANCY E. KEMENY
THEODORE S. LAWRENCE
Natural History of Liver Metastases 2353
Imaging of Hepatic Metastases 2354
Resection: Technical Considerations 2354
Results of Hepatic Resection for Colorectal Cancer 2355
Results of Resection for Noncolorectal Cancers 2355
Hepatic Arterial Chemotherapy 2356
Toxicity of Hepatic Arterial Infusion Therapy with
Floxuridine 2358
Other Agents Used with Hepatic Arterial Infusion 2359
Adjuvant Therapy after Resection of Colorectal
Liver Metastases 2359
Neoadjuvant Chemotherapy 2360
Other Liver Tumors 2360
Contents I.YV
Hepatic Artery Infusion with Hepatic Venous Filtration 2360
Isolated Hepatic Perfusion 2361
Chemoembolization for Metastatic Cancer to the Liver 2367
Local Ablative Therapy 2362
Cryotherapy 2363
Radiofrequency Ablation 2363
Other Ablative Techniques 2364
Results of Whole Liver Irradiation ± Chemotherapy 2365
Conclusion 2366
section 4 Metastatic Cancer to the Bone 2368
MARK W. MANOSO
JOHN H. HEALEY
Presentation 2368
Pathophysiology 2369
Diagnostic Evaluation 2369
Imaging of Bone Lesions 2370
Therapeutic Goals 2372
Therapeutic Modalities 2371
section 5 Malignant Pleural and Pericardia! Effusions 2381
DAO M. NGUYEN
DAVID S. SCHRUMP
Malignant Pleural Effusion 2381
Malignant Pericardial Effusion 2387
section 6 Malignant Ascites 2392
RICHARD B. HOSTETTER
FRANCESCO M. MARINCOLA
DOUGLAS J. SCHWARTZENTRUBER
Diagnosis and Workup 2392
Treatment of Malignant Ascites 2393
Conclusion 2396
52
Hematopoietic Therapy 2399
section 1 Transfusion Therapy 2399
YANYUN WU
PETER L. PERROTTA
EDWARD L. SNYDER
Blood Component Therapy 2400
Transfusion Reactions and Complications 2406
Transfusion Transmitted Disease 2409
Use of Special Blood Products in Oncology Patients 2410
Apheresis 242 2
Effect of Growth Factors on Transfusion Medicine 2422
Blood Substitutes 2422
sectio\ 2 Autologous Stem Cell Transplantation 2414
DENNIS L. COOPER
STUART SEROPIAN
History 2415
Stem Cell Mobilization 2425
Inadequate Mobilization of Stem Cells 2416
Tumor Contamination 2418
Practical Considerations for the Potential Autologous Stem Cell Patient 2419
High Dose Therapy Regimens: New Directions 2419
Late Toxicity: Myelodysplasia and Secondary Leukemia 2421
Future Directions 2421
section 3 Allogeneic Hematopoietic Stem Cell Transplantation 2423
RICHARD W. CHILDS
Conditioning Regimens 2424
Graft Versus Leukemia Effect 2425
Mechanisms of Graft Versus Leukemia Effect 2427
Complications of Allogeneic Hematopoietic Stem Cell Transplantation 2427
Epstein Barr Virus Lymphoproliferative Disorder 2429
Sources of Allogeneic Hematopoietic Stem Cells 2432
Results of Conventional Allogeneic Transplantation for Hematologic Malignancies 2434
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation 2435
Future Prospects 2439
section 4 Hematopoietic Growth Factors 2442
JENNIFER L. HOLTER
HOWARD OZER
Overview of Hematopoiesis and Hematopoietic Growth Factors 2442
Clinical Use of Recombinant Erythropoietin in Cancer Therapy 2448
Anemia Related to Myeloproliferative Disorders 2450
Predictors of Recombinant Erythropoietin Therapy Response 2451
Clinical Use of Recombinant Granulocyte Colony Stimulating Factors
in Cancer Therapy 2452
Clinical Use of Recombinant Interleukin 11 in Cancer Therapy 2455
Hematopoietic Growth Factors in Development 2456
Conclusion 2456
53
Infections in the Cancer Patient 2461
BRAHM H. SEGAL
THOMAS J. WALSH
JUAN C. GEA BANACLOCHE
STEVEN M. HOLLAND
Factors Predisposing Cancer Patients to Infection 2462
Bacterial Infections in Cancer Patients 2465
Fungal Infections 2469
Viral Infections 2477
Parasitic Infections 2484
Contents Iwii
Neutropenic Fever 2486
Syndromes 2496
Immune Augmentation Strategies 2506
54
Adverse Effects of Treatment 2515
section 1 Nausea and Vomiting 2515
ANN M. BERGER
REBECCA A. CLARK SNOW
Nature of the Problem 2515
Pathophysiology of Nausea and Vomiting 2515
Emetic Syndromes 2517
Control of Emesis and Risk Factors 2518
Antiemetic Agents 2519
Treatment Options Based on Emesis Category 2520
New Agents 2520
Radiation Induced Nausea and Vomiting 2521
Nausea and Vomiting Secondary to Comorbid Conditions 2522
Improving Antiemetic Control 2522
section 2 Oral Complications 2523
ANN M. BERGER
JANE M. FALL DICKSON
Oral Complications 2523
Sequelae of Oral Complications 2525
Strategies for Prevention and Treatment of Oral Complications 2526
Future Research Directions 2533
Conclusion 2533
section 3 Pulmonary Toxicity 2535
DIANE E. STOVER
ROBERT J. KANER
Radiation Induced Pulmonary Toxicity 2535
Radiation Related Bronchiolitis Obliterans with Organizing Pneumonia 2538
Chemotherapy Induced Pulmonary Toxicity 2539
section 4 Cardiac Toxicity 2545
JOACHIM YAHALOM
CAROL S. PORTLOCK
Anthracyclines 2545
Mitoxantrone 2547
Cyclophosphamide 2547
Ifosfamide 2547
Taxanes 2547
Trastuzumab 2548
Fluoropyrimidines 2549
Radiation Induced Heart Disease 2549
Conclusion 2553
section 3 Hair Loss 2556
ANN M. BERGER
JOYSON KARAKUNNEL
Anatomy and Physiology 2556
Classification 2556
Staging 2557
Diagnosis 2557
Treatment 2557
Conclusion 2559
section 6 Gonadal Dysfunction 2560
MARVIN L. MEISTRICH
RENA VASSILOPOULOU SELLIN
LARRY I. LIPSHULTZ
Effects of Cytotoxic Agents on Adult Men 2560
Effects of Cytotoxic Agents on Adult Women 2563
Effects of Cytotoxic Agents on Children 2566
Gonadal Dysfunction after Cranial Irradiation 2566
Preservation of Fertility, Hormone Levels, and Sexual Function 2567
Prevention and Management of Erectile and Ejaculatory Dysfunction 2570
Genetic Concerns 2571
Counseling 2572
section 7 Second Cancers 2575
FLORA E. VAN LEEUWEN
LOIS B. TRAVIS
Methods to Assess Second Cancer Risk 2575
Carcinogenicity of Individual Treatment Modalities 2576
Risk of Second Malignancy in Patients with Selected Primary Cancers 2580
Conclusion 2598
sectio\ 8 Miscellaneous Toxicities 2602
RAYMOND B. WEISS
Neurotoxicity 2603
Nephrotoxicity 2607
Hepatotoxicity 2610
Hypersensitivity Reactions 2611
Vascular Toxicity 2612
55
Supportive Care and Quality of Life 2615
section 1 Management of Cancer Pain 2615
KATHLEEN M. FOLEY
Epidemiology 2615
Barriers to Cancer Pain Management 2616
Definition of Pain 2617
Anatomy and Physiology of Pain 2617
Types of Pain 2618
Temporal Aspects of Pain 2619
Contents l\i\
Intensity of Pain 2619
Measurement of Pain 2619
Classification of Patients with Cancer Pain 2621
Common Pain Syndromes 2624
Clinical Assessment of Pain 2624
Management of Cancer Pain 2627
Analgesic Drug Therapy 2627
Classes of Drugs 2630
Psychological Approaches 2639
Anesthetic and Neurosurgical Approaches 2639
Physiatric Approaches 2645
Sedation in the Imminently Dying 2645
Algorithm for Cancer Pain Management 2646
Future Directions 2646
section 2 Nutritional Support 2649
J. STANLEY SMITH
DAVID FRANKENFIELD
WILEY W. SOUBA
Dysgeusia 2649
Weight Loss and Cancer Cachexia 2650
Nutrition Support for Weight Loss and Cancer Cachexia 2651
Nutrition and Tumor Growth 2651
Nutritional Assessment of the Cancer Patient 2652
Indications for Nutrition Support 2652
Parenteral versus Enteral Nutrition in Cancer Patients 2652
Specific Indications for the Use of Total Parenteral Nutrition in the
Cancer Patient 2653
Improving the Efficacy of Current Feeding Regimens 2658
Techniques of Providing Nutritional Support 2659
Conclusion 2661
section 3 Sexual Problems 2662
PATRICIA A. GANZ
MARK S. LITWIN
BETH E. MEYEROWITZ
Sexual Health and Physiology 2662
Sexual Problems and Their Prevalence among the General Population 2663
Impact of Cancer and Its Treatment on Sexual Health 2664
Specific Treatments 2665
Sexual Problems Associated with Specific Cancers 2668
Strategies for Assessment and Intervention 2671
Conclusion 2673
section 4 Genetic Counseling 2676
ELLEN T. MATLOFF
Why Is Cancer Genetic Counseling Necessary? 2676
Who Is a Candidate for Cancer Genetic Counseling? 2677
Components of the Cancer Genetic Counseling Session 2677
Issues in Cancer Genetic Counseling 2680
Future Directions 2681
IXX Contents
section 5 Psychological Issues 2683
BETH L. DINOFF
JOHN L. SHUSTER
Phases of Illness 2683
Psychological Complications of Cancer 2685
Therapies 2688
section 6 Community Resources 2691
BONNIE A. INDECK
Initial Diagnosis of Cancer 2691
Social Support Network 2691
Emotional Support 2691
Information Support 2693
Internet 2693
Computer Groups 2694
Instrumental Support 2694
Trends Affecting Demand for Community Services 2695
Survivorship 2696
Appendix: Common Community Resources 2696
section 7 Specialized Care of the Terminally III 2702
JANET L. ABRAHM
Discussing Prognosis 2702
Advance Care Planning 2703
Hope 2703
Barriers That Inhibit Advance Care Planning
Discussions 2704
Curiosity 2704
Healing versus Curing 2704
How to Tell the Children 2 704
Cultural/Religious Considerations 2705
Care without Chemotherapy 2706
Palliative Care Program 2706
Hospice Programs 2707
Relief of Suffering 2708
The Final Days 2714
After the Death 2715
Grief and Bereavement 2725
Conclusion 2717
56
Rehabilitation of the Cancer Patient 2719
LYNN H. GERBER
MARY M. VARGO
REBECCA G. SMITH
Impact of Cancer Treatment on Function 2720
Rehabilitation Interventions 2725
Contents \\\\
Rehabilitation Hospitalization and Basic Functional Independence 2732
Vocational Issues 2733
Rehabilitation Treatments of Specific Tumors 2734
57
Societal Issues in Oncology 2747
section 1 Ethical Issues 2747
CHRISTOPHER K. DAUGHERTY
Ethical Issues in Clinical Care in Oncology 2747
Ethical Issues in Cancer Clinical Trials 2752
Conclusion 2757
section 2 Economic Issues 2759
ALBERT B. EINSTEIN, JR.
U.S. Health Care Economy 2759
Medicare Cost Containment Efforts 2759
Medicare Reimbursement for Cancer Services 2760
Medicaid Cost Containment Efforts 2767
Insurance Industry Cost Containment Efforts 2767
Hospital Economic Issues 2762
Physician Economic Issues 2762
National Cancer Institute Designated and University Cancer Centers
Economic Issues 2763
Clinical Research 2763
Impact of Genomics 2764
Complementary and Alternative Medicine 2765
Standardization of Practice 2765
Health Economics and the Economic Burden of Cancer 2765
The Future 2766
section 3 Regulatory Issues 2767
GRANT A. WILLIAMS
PATRICIA KEEGAN
NEIL R. P. OGDEN
RICHARD PAZDUR
ROBERT TEMPLE
MARK MCCLELLAN
History of U.S. Food and Drug Administration Regulation of Drugs
and Biologies 2767
U.S. Food and Drug Administration Oversight of Clinical Trials for
Drugs and Biologies 2768
Basis for Cancer Drug Approval 2769
Drug Safety Reporting and Evaluation 2773
Access to Investigational Drugs 2773
Biologic Drug Products: Special Considerations 2773
Regulation of Devices for Cancer Treatment and Diagnosis 2774
U.S. Food and Drug Administration Initiatives and Guidances Expediting
Approval of Cancer Drugs, Biologies, and Devices 2776
Ixxii Contents
section 4 Telemedicine 2777
RICHARD M. SATAVA
JONATHAN D. LINKOUS
JAY H. SANDERS
Applications of Telemedicine 2778
Telemedicine in Other Countries 2779
Telemedicine in Oncology Care—Current Practices 2779
Telesurgery 2779
Telemedicine Impact on National Medical Policy 2780
Barriers and Challenges 2780
Conclusion 2781
section 5 International Differences in Oncology 2782
OLIVIER RIXE
PETER HARPER
DAVID KHAYAT
Developing Nations 2782
Cancers and Mortality: Differences in the More Developed Countries 2782
Screening 2783
Anticancer Drug Development throughout the World 2784
Drug Approval Process 2784
Cancer Treatment Strategy: European and United States Differences 2784
Differences in Cancer Survival 2784
Access to Cancer Care in Developed Nations 2785
Training as an Oncologist 2786
Research 2786
"Truth Telling": Differences between Nations 2786
Cancer in the Elderly 2787
Conclusion 2787
section 6 The National Cancer Program 2788
ANDREW C. VON ESCHENBACH
National Cancer Institute as Steward of the National Cancer
Program 2789
Harnessing the Power of Molecular Epidemiology 2789
Developing an Integrative Understanding of Cancer Biology 2790
Providing Bioinformatics Infrastructure 2790
Developing Prevention, Early Detection, and Prediction Approaches 2790
Facilitating the Development of Cancer Interventions 2791
Creating an Integrated Clinical Trials System 2792
Overcoming Health Disparities 2791
A Critical "Enterprise Wide" Opportunity: Technology Development and
Integration 2792
Integrative Computational Biology and Bioinformatics 2792
Advanced Imaging 2792
Bioengineering and Advanced Prototyping 2792
Development and Preclinical Testing of Prevention and Therapeutic
Agents 2792
Shared Research Resources 2793
Conclusion 2793
Contents lv\iii
58
Information Systems in Oncology 2795
DANIEL R. MASYS
The Internet 2796
Electronic Medical Records 2799
Conclusion 2802
59
Complementary, Alternative, and Integrative Therapies in Cancer Care 2805
ETHAN M. BASCH
CATHERINE E. ULBRICHT
Background 2805
Safety Concerns 2806
Patient Clinician Communication 2808
Specific Complementary and Alternative Medicine Therapies 2809
Therapies Used for Cancer Treatment and Secondary Prevention 2809
Therapies Used for Supportive Care 2812
Therapies Used for Primary Cancer Prevention 2813
part4t
NEWER APPROACHES IN CANCER TREATMENT
60
Gene Therapy 2819
PATRICK HWU
Methods of Gene Transfer 2819
Gene Marking Studies 2824
Genetic Modification of the Immune Response 2826
Modification of Tumors with Genes That Have Direct Antitumor Effects 2830
Selective Replication of Virus in Tumors 2832
Introduction of Genes into Normal Tissues to Protect Them from Chemotherapy or Radiotherapy 2832
Antiangiogenic Gene Therapy 2833
Molecular Imaging of Gene Modified Cells 2834
Conclusion 2834
61
Cancer Vaccines 2839
section 1 Preventive Vaccines 2839
DOUGLAS R. LOWY
JOHN T. SCHILLER
Background 2839
lx\iv Contents
Infectious Agents and Cancer 2839
Prophylactic versus Therapeutic Vaccination 2841
Hepatitis B Virus 2842
Human Papillomavirus 2843
Helicobacter pylori 2845
secti()\ 2 Therapeutic Vaccines 2846
NICHOLAS P. RESTIFO
JONATHAN J. LEWIS
Elicitation of Tumor Specific Immune Responses 2846
Identification of Tumor Associated Antigens Suitable for
Therapeutic Targeting 2846
Enhancement of Tumor Antigen Immunogenicity by Modification of
Epitope Sequences 2847
Early Models Using Therapeutic Cancer Vaccines 2848
Consistent Increases in Tumor Specific T Cells without Consistent
Clinical Responses 2848
How Are We Doing in Clinical Trials? 2848
Lessons from Melanoma 2849
Clinical Trial Data 2850
Immune Responses Do Not Always Translate into Clinical Responses—
Proposed Mechanisms of Tumor Escape 2853
Future Directions: A Focus on T Cell Activation and Death 2853
Conclusion 2854
62
Cell 'transfer Therapy 2857
MARK E. DUDLEY
STEVEN A. ROSENBERG
Background 2857
Preclinical Studies of Adoptive Cell Transfer 2858
Clinical Trials 2858
Tumor Infiltrating Lymphocytes 2860
Adoptive Cell Transfer Therapy after Lymphodepleting Chemotherapy in Patients
with Melanoma 2860
Additional Studies 2862
63
Antiangiogenesis Agents 2865
JUDAH FOLKMAN
Angiogenic Switch 2865
Endogenous Angiogenesis Inhibitors 2867
Rationale for Antiangiogenic Therapy of Cancer 2867
Antiangiogenic (Metronomic) Chemotherapy 2869
Future Directions 2879
Ciiiilnils l\\\
64
Focused Ultrasound 2883
FERENC A. JOLESZ
KULLERVO H. HYNYNEN
Fundamental Principles of Focused Ultrasound Surgery 2883
Interaction between Tissue and the Ultrasound Beam 2884
Magnetic Resonance Imaging Guidance for Thermal Ablations 2884
Magnetic Resonance Imaging Guided Focused Ultrasound Therapy
Delivery Systems 2885
Clinical Applications 2886
Conclusion 2889
65
Antisense Inhibition of Gene Expression 2891
C. A. STEIN
LUBA BENIMETSKAYA
SRIDHAR MANI
Oligonucleotide Stability and Efficacy: The Role of Phosphorothioates 2892
Mechanism of Action of the Antisense Effect 2894
Delivery of Oligonucleotides into Cells 2895
Pharmacokinetics 2896
Clinical Studies 2896
Clinical Trials of G3139 2897
Index 1 1 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author2 | DeVita, Vincent T. Jr. 1935- |
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| edition | 7. ed. |
| format | Electronic eBook |
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| illustrated | Not Illustrated |
| index_date | 2024-07-02T14:14:21Z |
| indexdate | 2024-07-09T20:37:08Z |
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| language | English |
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| spelling | Cancer principles & practice of oncology ed. by Vincent T. DeVita ... 7. ed. Philadelphia [u.a.] Lippincott Williams & Wilkins 2005 1 Online-Ressource txt rdacontent c rdamedia cr rdacarrier Systemvoraussetzungen: Internet-Anschluss Neoplasms Krebs Medizin (DE-588)4073781-0 gnd rswk-swf Krebsforschung (DE-588)4165564-3 gnd rswk-swf Onkologie (DE-588)4075658-0 gnd rswk-swf Onkologie (DE-588)4075658-0 s DE-604 Krebs Medizin (DE-588)4073781-0 s Krebsforschung (DE-588)4165564-3 s 1\p DE-604 DeVita, Vincent T. Jr. 1935- (DE-588)13564240X edt Erscheint auch als Druck-Ausgabe Cancer http://gateway.ovid.com/ovidweb.cgi?T=JS&MODE=ovid&NEWS=n&PAGE=booktext&D=books&SC=00139877 Agentur Volltext HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014713924&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Cancer principles & practice of oncology Neoplasms Krebs Medizin (DE-588)4073781-0 gnd Krebsforschung (DE-588)4165564-3 gnd Onkologie (DE-588)4075658-0 gnd |
| subject_GND | (DE-588)4073781-0 (DE-588)4165564-3 (DE-588)4075658-0 |
| title | Cancer principles & practice of oncology |
| title_auth | Cancer principles & practice of oncology |
| title_exact_search | Cancer principles & practice of oncology |
| title_exact_search_txtP | Cancer principles & practice of oncology |
| title_full | Cancer principles & practice of oncology ed. by Vincent T. DeVita ... |
| title_fullStr | Cancer principles & practice of oncology ed. by Vincent T. DeVita ... |
| title_full_unstemmed | Cancer principles & practice of oncology ed. by Vincent T. DeVita ... |
| title_short | Cancer |
| title_sort | cancer principles practice of oncology |
| title_sub | principles & practice of oncology |
| topic | Neoplasms Krebs Medizin (DE-588)4073781-0 gnd Krebsforschung (DE-588)4165564-3 gnd Onkologie (DE-588)4075658-0 gnd |
| topic_facet | Neoplasms Krebs Medizin Krebsforschung Onkologie |
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