Holland-Frei Cancer Medicine

Donald W Kufe; Raphael E Pollock; Ralph R Weichselbaum; Robert C Bast, Jr; Ted S Gansler; James F Holland; Emil Frei, III

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Holland-Frei Cancer Medicine, 6th edition

Editors: Donald W Kufe, MD, Raphael E Pollock, MD, PhD, Ralph R Weichselbaum, MD, Robert C Bast, Jr, MD, Ted S Gansler, MD, MBA, James F Holland, MD, ScD (hc), and Emil Frei, III, MD.

Editor Information

Hamilton (ON): BC Decker; 2003.

ISBN-10: 1-55009-213-8

Excerpt

The editors have strived to make every chapter in this book present the composite of relevant science and of clinical knowledge about each cancer. The evolution of disease in the patient is critical to appreciating the special molecular characteristics of that particular type of cancer cell.

The practice of cancer medicine in its broadest sense will move forward from the threshold most effectively when the science that has been accomplished and that is evolving is joined at the hip, inseparably, with clinical knowledge of the disease and how it disables the patient. Cancer Medicine-6 offers such a synthesis.

Contributors
Preface
Part I Cardinal Manifestations
- Chapter 1. Cardinal Manifestations of Cancer
  James F. Holland.
Part II Scientific Foundation
- Section 1: Cancer Biology
  - Chapter 2. Molecular Biology, Genomics, and Proteomics
    Kornelia Polyak and Matthew Meyerson.
    - Overview: Gene Structure
      - Genes and Gene Expression
      - Functional Components of the Gene
      - Structural Considerations
      - Summary
    - General Techniques
      - Restriction Endonucleases and Recombinant DNA
      - Gene Probes and Hybridization
      - Summary
    - Gene Analysis: DNA
      - Southern Blotting
      - Nucleotide Sequencing
      - Polymerase Chain Reaction
      - DNA Polymorphisms
      - Summary
    - Gene Expression: MRNA Transcript Analysis
      - Structural Considerations
      - Northern Blotting
      - cDNA
      - Serial Analysis of Gene Expression
      - DNA Microarray Analysis
      - Polymerase Chain Reaction
      - Ribozymes and RNA Interference
      - Summary
    - Gene Expression: Protein Analysis
      - Structural Considerations
      - Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis
      - Immunoblotting
      - Immune Precipitation
      - Enzyme-Linked Immunosorbent Assay
      - Sequencing
      - Mass Spectrometry
      - Engineered Protein Expression
      - Summary
    - References
  - Chapter 3. Cell Proliferation and Differentiation
    Michael Andreeff, David W. Goodrich, and Arthur B. Pardee.
    - Proliferation
      - Tumor Growth and Cell Proliferation In Vivo
      - Cell-Cycle Control
      - The G₀ to S Checkpoints
      - DNA Damage–Induced Checkpoints
      - Checkpoint Defects in Tumor Cells
    - Apoptosis and Proliferation
    - Differentiation
      - Differentiation and Cell Proliferation
      - Stem Cells
      - Extracellular Factors That Control Differentiation
      - Intracellular Regulators
      - DNA Methylation
      - Differentiation and Cancer Therapy
    - Acknowledgment
    - References
  - Chapter 4. Apoptosis and Cancer
    John C. Reed.
    - Apoptosis Caused by Caspases
    - Caspase Activation Pathways: an Overview
    - Protein Domains Involved in Apoptosis Regulation
      - Death Domain Proteins
      - Death Effector Domain (DED) Proteins
      - CARD-family Proteins
      - IAP Family Proteins
      - Bcl-2 Family Proteins
    - Signal Transduction and Apoptosis Dysregulation in Cancer
      - NFκB
      - AKT
    - Therapeutic Opportunities from Apoptosis Research
    - Acknowledgments
    - References
  - Chapter 5. Growth Factors and Signal Transduction in Cancer
    Anna Bafico and Stuart A. Aaronson.
    - Background
    - Growth Factor Receptors with Tyrosine Kinase Activity
    - Classification of Growth Factors and Their Receptors
      - Platelet-Derived Growth Factor Family
      - Vascular Endothelial Growth Factor Family
      - Epidermal Growth Factor Family
      - Fibroblast Growth Factor Family
      - The Insulin Family
      - Hepatocyte Growth Factor
      - Neurotrophin Family
      - The Ephrin Family
      - Agrin Family
      - GDNF Family
      - Angiopoietins
      - Discoidin Domain Receptors
      - Orphan Receptors
    - Abnormalities Associated with Growth Factors in Cancer Cells
    - Aberrations Affecting Growth Factor Receptors in Tumor Cells
    - Signaling Pathways of Tyrosine Kinase Receptors
      - PI-3-Kinase and Survival Signaling
      - PI-3-Kinase Signaling in Cancer
      - RAS
      - Raf and Cancer
      - Other MAP Kinases
    - Implications for Cancer Therapy
    - References
  - Chapter 6. Oncogenes
    Marco A. Pierotti, Gabriella Sozzi, and Carlo M. Croce.
    - Discovery and identification of oncogenes
      - Oncogenes, protooncogenes, and their functions
      - Growth Factors
      - Growth Factor Receptors
      - Signal Transducers
      - Transcription Factors
      - Programmed Cell Death Regulation
    - Mechanisms of oncogene activation
      - Mutation
      - Gene Amplification
      - Chromosomal Rearrangements
    - Oncogenes in the initiation and progression of neoplasia
    - Summary and conclusions
    - References
  - Chapter 7. Tumor-Suppressor Genes
    Ben Ho Park and Bert Vogelstein.
    - Genetic Basis for Tumor Development
    - Somatic Cell Genetic Studies of Tumorigenesis
    - Retinoblastoma—A Paradigm for Tumor-Suppressor Gene Function
      - Cloning and Analysis of the RB1 Gene
      - Function of the Retinoblastoma Protein (p105-RB)
    - The p53 Gene
      - p53 Function
    - The INK4A Locus and the p16 ^INK4A and p19 ^ARF Genes
    - The APC Gene
      - Identification of the APC Gene and Germ Line Mutations
      - Somatic APC Mutations in Sporadic Colon Tumors
      - APC Function
    - BRCA1 and BRCA2 Genes
    - WT1 Gene
    - NF1 and NF2 Genes
      - NF1 Gene
      - NF2 Gene
    - VHL Gene
    - DNA Repair Pathway Genes
      - DNA Mismatch Repair Gene Defects and HNPCC
    - Candidate Tumor-Suppressor Genes
    - Summary
    - References
  - Chapter 8. Recurring Chromosome Rearrangements in Human Cancer
    Denise A. Levitan, Rita Nanda, Janet D. Rowley, and Olufunmilayo I. Olopade.
    - Myeloproliferative Disorders
      - Chronic Myeloid Leukemia
      - Acute Myeloid Leukemia De Novo
      - Other Myeloproliferative Diseases
    - Acute Myeloid Leukemia and Myelodysplastic Syndrome Associated with Prior Cytotoxic Therapy
      - Primary Myelodysplastic Syndrome
      - Lymphoma
      - Chronic Lymphoproliferative Disorders
      - Acute Lymphoblastic Leukemia
      - T Cell Disorders
      - Solid Tumors
      - Benign Tumors
      - Malignant Tumors
    - How And Why Recurring Chromosomal Abnormalities Occur
      - Biologic Consequences of Consistent Chromosome Abnormalities
      - Molecular Analysis of Recurring Chromosome Abnormalities
    - Acknowledgment
    - References
  - Chapter 9. Biochemistry of Cancer
    Raymond W. Ruddon.
    - Historical Perspectives
    - What Makes a Cancer Cell a Cancer Cell?
      - Phenotypic Alterations in Cancer Cells
      - Genetic Alterations in Cancer Cells
      - Alterations of Cellular Differentiation in Cancer
      - Alterations in Signal-Transduction Mechanisms
      - Alterations of Cell-Cycle Regulation and Apoptosis
    - Acknowledgments
    - References
  - Chapter 10. Invasion and Metastases
    Lance A. Liotta and Elise C. Kohn.
    - Tumor-Host and Tumor-Stromal Interactions
    - Adhesion
      - Cadherins
      - Integrins
    - Proteolysis
      - Matrix Metalloproteinases
      - Plasminogen Activator Family
    - Tumor Cell Migration
    - Angiogenesis
    - Genetic Regulation of Invasion and Metastasis
      - Metastasis-Suppressor Genes
    - Novel Technologies Advance Identification of Metastasis and Invasion-Promoting Genes and Gene Products
    - Invasion as a Therapeutic Molecular Target
      - Receptor Tyrosine Kinase Metastasis Targets and Other Kinase Targets
      - Antiadhesive Agents
      - Protease Inhibitors
      - Antiangiogenesis Therapies
      - Antimetastasis Signal-Transduction Therapy
      - Chronic Low-Dose Chemotherapy Treatment
    - Summary
    - References
  - Chapter 11. Tumor Angiogenesis
    Judah Folkman and Raghu Kalluri.
    - Historic background
    - Beginning of angiogenesis research
      - Hypothesis: tumor growth depends on angiogenesis
      - Experimental evidence
      - Metastasis is also angiogenesis dependent
      - Prevascular phase limits tumor expansion
      - Human tumors and spontaneous animal tumors switch to an angiogenic phenotype
      - Principles of angiogenesis important for clinical translation
    - Acknowledgments
    - References
- Section 2: Cancer Immunology
  - Chapter 12. Tumor Antigens
    Hassane M. Zarour, Albert DeLeo, Olivera J. Finn, and Walter J. Storkus.
    - Categories of Tumor Antigens
    - Melanoma Antigens
    - Cancer-Testis (CT) Antigens
    - Epithelial Tumor Antigens
    - Cell Cycle Regulatory Proteins as Tumor Antigens
    - Idiotypes as Tumor Antigens
    - Application of Tumor Antigens for Clinical Immunotherapy
      - Melanoma Antigens for Clinical Immunotherapy
      - CT Antigens for Clinical Immunotherapy
      - Epithelial Tumor Antigens for Clinical Immunotherapy
      - Cell Cycle Regulatory Proteins for Clinical Immunotherapy
      - Idiotypes in Clinical Immunotherapy
    - Summary
    - Acknowledgments
    - References
  - Chapter 13. Tumor Markers and Immunodiagnosis
    William Bigbee and Ronald B. Herberman.
    - Categories and Applications of Tumor Markers
    - Traditional Tumor Markers
    - Characteristics of the Ideal Tumor Marker
    - Risk Markers
    - Screening and Early Detection Markers
    - Diagnostic Markers
    - Prognostic Markers
    - Therapy Selection and Response Markers
    - Recurrence and Metastasis Markers
    - Organ Site-Specific Markers
      - Bladder
      - Breast
      - Colon
      - Gestational Trophoblastic Disease and Testicular Germ Cell Tumors
      - Lung
      - Ovary
      - Prostate
    - New Approaches and Technologies
    - Conclusion
    - Acknowledgments
    - References
  - Chapter 14. Effectors of Immunity and Rationale for Immunotherapy
    Theresa L. Whiteside and Ronald B. Heberman.
    - Antitumor Effector Cells in Humans
    - T Lymphocytes
      - Tumor-Infiltrating T cells
      - Circulating T Cells in Patients with Cancer
      - Apoptosis of CD8+ T Cells in the Circulation of Patients with Cancer
      - Selective Apoptosis of Antitumor Effector Cells
    - Assessment of T-Cell Effectors in Patients with Cancer
      - Natural Killer Cells
      - Macrophages
    - Implications of Effector Cell Dysfunction in Cancer
    - Rationale for Immunotherapy of Cancer
    - References
  - Chapter 15. Tumor-Associated Immunodeficiency and Implications for Tumor Development and Prognosis
    William H. Chambers, Hannah Rabinowich, and Ronald B. Herberman.
    - Documentation of Immune Suppression in Cancer Patients
    - Mechanisms of Immunosuppression
      - Soluble Factors Released by Tumor Cells
      - Elimination of Immune Effector Cells
      - Disruption of Signaling Pathways in Immune Cells
      - Mechanisms of Resistance of Tumor Cells to Cytotoxicity
      - Evasion of Immune Reactivity by Tumor Cells
    - Conclusions
    - References
- Section 3: Cancer Etiology
  - Chapter 16. Genetic Predisposition to Cancer
    Marcia S. Brose, Thomas C. Smyrk, Barbara Weber, and Henry T. Lynch.
    - Genetic Basis of Cancer Syndromes
      - Breast-Ovarian Cancer Syndrome
      - Colorectal Carcinoma
      - Li-Fraumeni Syndrome
      - Malignant Melanoma
      - Multiple Endocrine Neoplasia
      - Neurofibromatosis
      - Retinoblastoma
      - Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
      - von Hippel-Lindau Disease
      - Wilms Tumor
    - Cancer-Associated Genodermatoses
      - Ataxia-Telangiectasia
      - Bloom Syndrome
      - Cowden Syndrome and the Multiple Hamartoma Syndromes
      - Fanconi Anemia
      - Werner Syndrome
      - Xeroderma Pigmentosum
    - Other Cancers with Familial Clusterings
      - Familial Pancreatic Cancer
      - Familial Gastric Cancer
      - Familial Risk Factors
      - Hereditary Gastric Carcinoma
      - Hereditary Diffuse Gastric Cancer
      - Familial Prostate Cancer
      - Lung Cancer
      - Renal Cell Carcinoma
      - Familial Neuroblastoma
      - Hematologic Malignancy
      - Acute Myelogenous Leukemia
      - Chronic Lymphocytic Leukemia
      - Multiple Myeloma
      - Hodgkin Disease and Non-Hodgkin Lymphoma
      - X-Linked Lymphoproliferative Syndrome
    - Clinical Translation
      - Overview
      - Medicolegal Issues
    - Conclusions/Future Directions
    - References
  - Chapter 17. Chemical Carcinogenesis
    Ainsley Weston and Curtis C. Harris.
    - Multistage Carcinogenesis
      - Tumor Initiation
      - Tumor Promotion
      - Malignant Conversion
      - Tumor Progression
    - Gene-Environment Interactions and Interindividual Variation
      - Caretaker and Gatekeeper Genes
    - Carcinogen Metabolism
    - DNA Damage and Repair
    - Mutator Phenotype
    - Clonal Evolution
    - Oncogenes and Tumor-Suppressor Genes
    - Assessment of Causation by the Bradford-Hill Criteria
    - Implications for Molecular Epidemiology, Risk Assessment, and Cancer Prevention
    - Acknowledgments
    - References
  - Chapter 18. Hormones and the Etiology of Cancer
    Brian E. Henderson, Leslie Bernstein, and Ronald K. Ross.
    - Breast Cancer
      - Reproductive Factors
      - Age at First Birth
      - Diet
      - Exogenous Hormones
      - Genetic Determinants
    - Endometrial Cancer
      - Mitotic Activity in the Endometrium
      - Estrogen Replacement Therapy
      - Body Weight
      - Oral Contraceptives
      - Parity
    - Ovarian Cancer
      - Parity
      - Oral Contraceptives
    - Prostate Cancer
      - Genetic Basis for Androgen Involvement in Prostate Cancer Development
    - Adolescent and Young Adult Genital Cancer
      - Vaginal Adenocarcinoma
      - Testis Cancer
    - Cervical Cancer
    - Thyroid Cancer
    - Osteosarcoma
    - Conclusion
    - References
  - Chapter 19. Ionizing Radiation
    John B. Little.
    - Development of Radiation Injury
    - Principal Cellular and Tissue Effects of Radiation
      - Cell Killing
      - Mutagenesis
      - Chromosomal Aberrations
      - Neoplastic Transformation In Vitro
      - Radiation-Induced Genomic Instability
      - Bystander Effects in Irradiated Cell Populations
    - Molecular Mechanisms
      - DNA Damage and Genetic Changes
      - Tumor-Suppressor Genes
      - Oncogenes
    - Experimental Radiation-Induced Carcinogenesis
      - General Characteristics of Radiation Carcinogenesis
      - Dose-Response Relationships
      - Modifying Factors
      - Genetic Susceptibility to Radiation-Induced Cancer
    - Human Epidemiologic Studies
      - Leukemia
      - Other Tumors
      - Radiation-Induced Secondary Tumors
      - Low-Dose Exposures
    - Risk Assessment
    - Acknowledgments
    - References
  - Chapter 20. Ultraviolet Radiation Carcinogenesis
    James E. Cleaver and David L. Mitchell.
    - Historical Perspective
    - Epidemiology
      - Skin Cancer Frequency and Age of Onset
      - Sunlight Spectrum and Wavelengths Responsible for Skin Cancer
      - Sunlight-Induced Photoproducts in DNA
    - Genetic Factors in Skin Carcinogenesis
      - Excision of UV Photoproducts
      - Mutagenicity of UV Photoproducts and Low-Fidelity DNA Polymerases
      - Mechanism of Nucleotide Excision Repair
    - Xeroderma Pigmentosum
    - Cockayne Syndrome
    - Trichothiodystrophy
    - Carcinogenesis
    - References
  - Chapter 21. Physical Carcinogens
    Morando Soffritti, Franco Minardi, and Cesare Maltoni.
    - Known Physical Carcinogens
      - Hard and Soft Materials
      - Fibers
      - Nonfibrous Particulate Materials
      - Particulate Air Pollution
      - Gel Materials
    - Mechanisms of Carcinogenesis
    - Electromagnetic Fields
    - Trauma
    - Conclusions
    - References
  - Chapter 22. Tumor Viruses
    Robert C. Gallo and Marvin S. Reitz, Jr.
    - Classification
    - Structure
      - Long Terminal Repeat
      - Leader Sequence
      - GAG
      - POL
      - Envelope
      - Genomic Variation
    - Replication Cycle
    - Mechanisms of Oncogenesis
      - Oncogene Capture
      - Insertional Activation
      - Growth Stimulation and Two-Step Oncogenesis
      - Transactivation
    - Endogenous Retroviruses
    - Retroviral Vectors and Gene Therapy
    - Conclusions
    - References
  - Chapter 23. Herpesviruses
    Jeffrey I. Cohen.
    - Properties of Herpesviruses
    - Oncogenic Features of Herpesviruses
    - Epstein-Barr Virus: An Oncogenic Human Herpesvirus
      - Effect on B-Cell Growth In Vitro
      - Gene Expression in Transformed Lymphocytes
      - Epstein-Barr Virus Genes Expressed During Productive Infection
      - Animal Models
      - Clinical Aspects
    - Human Herpesvirus 8 and Malignancies
    - Viral Proteins
    - Clinical Aspects
      - Kaposi Sarcoma
      - Primary Effusion Lymphoma
      - Multicentric Castleman disease
      - Other Diseases
    - Oncogenic Potential of Other Human Herpesviruses
    - References
  - Chapter 24. Papillomaviruses and Cervical Neoplasia
    Christopher P. Crum and Catherine M. McLachlin.
    - Definitions, Tissue Specificity, and Mechanisms of Infection and Transformation
      - Definitions
      - Specificity
      - Mechanism of Infection
      - Mechanisms of Neoplastic Transformation
    - HPV and Human Genital Neoplasia
      - Risk Factors
      - Applications to Clinical Medicine
    - References
  - Chapter 25. Hepatitis Viruses
    Max W. Sung and Swan N. Thung.
    - Hepatitis B Virus
      - HBV and Hepatocellular Carcinoma
      - Primary Prevention
      - Secondary Prevention
    - Hepatitis C Virus
      - HCV and Hepatocellular Carcinoma
      - Prevention and Treatment
    - Hepatitis D Virus
      - Clinical Presentation
      - Prevention and Treatment
    - Hepatitis A Virus
      - Clinical Presentation
      - Prevention and Treatment
    - Hepatitis E Virus
      - Clinical Presentation
      - Prevention
    - Hepatitis F, G, and TT Viruses
    - References
  - Chapter 26. Parasites
    Piero Mustacchi.
    - Schistosomiasis and Cancer of the Bladder
      - Epidemiologic Aspects
      - Geography
      - Age and Sex
      - Urban/Rural Distribution
      - Frequency and Severity of Infection
      - Variability in Diagnostic Criteria of Schistosomiasis
      - Geographic Variability in Schistosomal Virulence
      - Progression of Bilharzial Bladder Cancer
      - Role of Urinary Infection
      - Pathology of Benign and Preneoplastic Schistosomal Bladder Lesions
      - Site of Origin
      - Histologic Classification
      - Experimental Data
      - Helminthic Infestations and Viruses
      - Metabolic Observations During Schistosomiasis
    - Schistosomiasis and Cancer of Other Sites
      - Large Intestine
      - Breast
      - Liver
      - Lymphoma
      - Other Organs
      - Evaluation of Carcinogenicity of Schistosomiasis
    - East Asian Distomiasis
      - Liver and Pancreas
      - Evaluation of Carcinogenicity of Distomiasis
    - Malaria
    - American Burkitt Lymphoma
    - Cancer in Animals
    - References
- Section 4: Cancer Epidemiology, Prevention, and Screening
  - Chapter 27. Cancer Epidemiology
    Michael J. Thun and Ahmedin Jemal.
    - Measures of Disease Occurrence
      - Age and Age Adjustment
    - Cancer Surveillance
      - Date Collection and Reporting
      - Age-Adjusted Incidence and Death Rates
      - Estimated Number of Cases and Deaths from Cancer
      - Individual Risk of Cancer
      - Validity of Cancer Surveillance Data
      - Temporal Trends in Cancer Occurrence in the United States
      - Variations Across Socioeconomic, Ethnic, and Racial Groups
    - Survival of Patients with Cancer
    - Studies of Cancer Etiology
    - Descriptive Studies
    - Analytic Epidemiology
    - Measures of Association
      - Cohort Studies
    - Case-Control Studies
    - What Constitutes “Proof” in Epidemiologic Studies?
    - IARC Classification of Carcinogens
    - Summary
    - References
  - Chapter 28. Prevention of Tobacco-Related Cancer
    Paul F. Engstrom, Margie L. Clapper, and Robert A. Schnoll.
    - Physiochemical Composition of Tobacco Smoke
    - Carcinogenic and Genotoxic Effects of Tobacco Constituents
    - Genetic Variation in Cancer Susceptibility
      - Phase I Enzymes
      - Phase II Enzymes
    - Approaches for Smoking Cessation
      - Self-Help Methods
      - Formal Smoking Cessation Clinics
      - Physician-Based Interventions
      - Harm Reduction
      - Tailoring Smoking Cessation Interventions for Special Populations
      - Smokeless Tobacco
      - Environmental Tobacco Smoke (ETS)
      - The Genetics of Tobacco Addiction
    - Prevention of Tobacco Use
    - Summary
    - References
  - Chapter 29. Nutrition in the Etiology and Prevention of Cancer
    Steven K. Clinton, Edward L. Giovannucci, and Elizabeth C. Miller.
    - Methodologic Issues in Diet, Nutrition, and Cancer Studies
      - Assessment of the Human Diet
      - Biologic Assessment of Nutrient Intake
      - Laboratory Models
    - Public Health Guidelines for Cancer Prevention
    - Summary of Research Efforts Focusing on Specific Cancers
      - Colon and Rectum
      - Breast Cancer
      - Prostate Cancer
      - Lung Cancer
      - Oral Cavity, Larynx, and Oropharynx Cancers
      - Esophageal Cancer
      - Stomach Cancer
      - Liver Cancer
      - Pancreatic Cancer
      - Endometrial Cancer
      - Ovarian Cancer
      - Bladder Cancer
    - Current Research
      - Specific Foods, Nutrients, and Dietary Components Frequently Associated with Cancer Prevention
      - Vitamins
      - Minerals
      - Foods and Food Components
    - Survivorship: Diet and Nutritional Guidance During and Following Cancer Treatment
      - Active Treatment Phase
      - Recovery Following Treatment
      - Advanced Cancer
      - Prevention of Cancer Recurrence and Long-term Complications of Therapy
    - References
  - Chapter 30. Chemoprevention of Cancer
    Michael B. Sporn and Scott M. Lippman.
    - Agents for Chemoprevention and Their Mechanism of Action
      - Types of Chemopreventive Agents
    - Chemoprevention Trials
      - Head and Neck
      - The Lung
      - Colon and Rectum
      - The Skin
      - The Breast
      - Esophagus and Stomach
      - The Bladder
      - The Cervix
    - Chemoprevention and Overall Cancer Incidence
    - References
  - Chapter 31. Cancer Screening and Early Detection
    Robert A. Smith, Curtis J. Mettlin, and Harmon Eyre.
    - Key Criteria in the Decision to Screen
      - Disease Burden
      - Characteristics of the Disease
      - Is the Screening Test Effective?
      - Cost Effectiveness
      - Acceptability to Individuals at Risk and Healthcare Providers
    - Methodologic Issues in the Evaluation of Early Detection Programs
      - Known Biases in the Evaluation of Screening Programs
      - Research Designs for Screening Evaluation
    - Breast Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Colorectal Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
      - Screening for Colorectal Cancer: Some Final Considerations
    - Lung Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Prostate Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Testicular Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Cervical Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Endometrial Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Ovarian Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Melanoma and Nonmelanoma Skin Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - Oral Cancer
      - Disease Burden
      - Screening and Diagnostic Methods
      - Screening Recommendations
    - The Cancer-Related Checkup
    - Conclusion
    - References
- Section 5: Clinical Trials and Outcomes Assessment
  - Chapter 32. Theory and Practice of Clinical Trials
    Marvin Zelen.
    - Types of Clinical Trials
      - Randomized versus Nonrandomized Clinical Trials
      - Multicenter versus Single-Center Trials
    - Planning Clinical Trials
      - Overall Considerations
      - Early Detection Clinical Trials
      - Statistical Tests and Probabilities of Reaching Incorrect Conclusions
    - Data Collection and Forms Design
    - Experimental Design
    - Role of Compliance
    - Interim Analyses, Multiple Looks at Data, and Early Stopping
    - Strategy of Experimentation
    - Reporting of Clinical Trials
      - General Guidelines
      - Statistical Techniques
      - Categorical Data
      - Survival Data
      - Test of Significance for Comparing Two Survival Distributions
    - Statistical Models
      - Logistic Models
      - Proportional Hazard Models for Survival (Cox Survival Models)
    - Meta-analysis
    - Falsification of Data
    - References
    - Additional Reading
      - The following books contain good overall discussions of clinical trials
      - The following books address special problems in clinical trials
  - Chapter 33. Statistical Innovations in Cancer Research
    Donald Berry.
    - Bayesian Updating
      - Assessing Degrees of Belief
      - Robustness Principle
      - Frequentist/Bayesian Comparison
      - Predictive Probabilities
      - Bayesian versus Frequentist Interim Analyses
    - Analysis Issues
      - Hierarchical Modeling: Synthesizing Information
      - Hazards over Time
    - Decision Analysis and Choosing Sample Size
    - Adaptive Designs of Clinical Trials
      - Continuous Reassessment Method (CRM) in Phase I
      - Adaptive Dose-finding in Phase II
      - Seamless Phases II and III
      - Adaptive Allocation
      - Process or Trial? Evaluating Many Drugs Simultaneously Using Adaptive Allocation
      - Extraim Analyses
    - Auxiliary Variables, Biomarkers, and Biological Agents
      - Using Auxiliary Variables
      - Developing Biological Agents
    - Acknowledgements
    - References
  - Chapter 34. Outcomes Assessment
    Jane C. Weeks.
    - Historical Perspective
    - Outcome Measures
      - Disease Outcomes
      - Quality of Life
      - Cost and Cost-Effectiveness
    - Study Designs
      - Cohort Studies
      - Clinical Trials
      - Decision Analysis
      - Cost-Effectiveness Analysis
    - Outcomes Studies in Oncology
      - Patterns and Quality of Care
      - Effectiveness
      - Cost-Effectiveness Studies
    - Outcomes Management
    - Summary
    - References
Part III Cancer Diagnosis
- Section 6: Cancer Pathology
  - Chapter 35. Principles of Cancer Pathology
    James L. Connolly, Stuart J. Schnitt, Helen H. Wang, Janina A. Longtine, Ann Dvorak, and Harold F. Dvorak.
    - Tumor Structure and Tumor Stroma Generation
      - Tumor Structure
      - Tumor Stroma Generation
    - Role of the Surgical Pathologist in the Diagnosis and Management of the Cancer Patient
      - Methods for Obtaining Specimens
      - Gross Handling of Specimens
      - Preparation of Microscopic Sections
      - Microscopic Interpretation of Tissue Sections
      - Ancillary Staining and Analytical Methods
      - Excision Margins
      - Tumor Grading, Staging, and Prognosis
      - Surgical Pathologist's Report
      - The Role of the Cytopathologist
      - Role of the Immunohistochemist
      - Role of the Electron Microscopist
      - Role of the Clinical Pathologist
      - Role of the Molecular Pathologist
      - Role of the Autopsy Pathologist
    - Summary and Conclusions
    - References
- Section 7: Imaging
  - Chapter 36. Principles of Imaging
    Edward F. Patz, Jr.
    - References
  - Chapter 36a. Imaging Cancer of Unknown Primary Site
    Kitt Shaffer.
    - References
  - Chapter 36b. Imaging Neoplasms of the Central Nervous System, Head, and Neck
    Christopher J. Hurt, David M. Yousem, and Norman J. Beauchamp, Jr.
    - Central Nervous System
      - The Brain
      - Spinal Cord
    - Head and Neck
      - Nasopharynx
      - Sinonasal Cavity
      - Oral Cavity
      - Oropharynx
      - Larynx
    - Lymphadenopathy
    - Extramucosal Masses
    - Conclusion
    - References
  - Chapter 36c. Imaging Neoplasms of the Thorax
    Jeremy J. Erasmus and H. Page McAdams.
    - Lung Cancer
      - Staging
      - Assessing Treatment Response
    - Mediastinal Masses
    - Malignant Pleural Mesothelioma
    - Conclusion
    - References
  - Chapter 36d. Imaging Neoplasms of the Abdomen and Pelvis
    Haesun Choi, Evelyne Loyer, Harmeet Kaur, and Paul M. Silverman.
    - Gastrointestinal Tract
    - The Liver
    - Biliary Duct
    - Carcinoma of the Pancreas
    - Imaging of Renal and Adrenal Tumors
    - Tumors of the Female Reproductive Tract
    - Prostate
    - Conclusion
    - References
  - Chapter 36e. Imaging of Musculoskeletal Neoplasms
    R. Lee Cothran and Clyde A. Helms.
    - References
  - Chapter 36f. Imaging the Breast
    Lawrence W. Bassett, Karen Conner, and MS, IV.
    - Types of Mammography
    - Standardized Mammography Reporting
      - Breast Tissue Composition
      - Findings
      - Overall Impression and Assessment Category
    - The Normal Mammogram
    - The Abnormal Mammogram
      - Masses
      - Calcifications
      - Indirect Signs of Malignancy
    - Mammography for Preoperative Planning
    - Mammography of the Postsurgical Breast
    - Ultrasonography
    - Imaging-Guided Needle Biopsy of the Breast
    - Other Breast Imaging Modalities
      - Digital Mammography
      - Magnetic Resonance Imaging of the Breast
      - Radionuclide Imaging
    - References
  - Chapter 36g. Ultrasonography: Its Role in Oncologic Imaging
    Stephanie R. Wilson.
    - Recent Advances
    - Tumor Detection and Characterization
    - Small Parts Scanning
      - The Scrotum
      - The Neck
      - The Breast
    - The Abdominal Organs
      - Liver Tumors
      - The Biliary Tract
      - The Kidney
      - The Pancreas
      - The Spleen
      - The Hollow Viscera
      - The Peritoneum
    - Gynecologic Organs
    - Prostatic and Transrectal Sonography
    - Central Nervous System Ultrasonography
    - Intraoperative Ultrasonography
    - Conclusion
    - References
  - Chapter 36h. Radionuclide Imaging in Cancer Medicine
    R. Edward Coleman.
    - Single-Photon Techniques
      - Bone Scanning
      - Gallium Scintigraphy
      - Thallium-201 and Technetium-99m Methoxyisobutyl Isonitrile
      - Monoclonal Antibody Imaging
      - Somatostatin Receptor Scintigraphy and Metaiodobenzylguanidine
    - Positron Emission Tomography
      - Lung Cancer
      - Colorectal Carcinoma
      - Malignant Melanoma
      - Lymphoma
      - Head and Neck Cancer
      - Esophageal Cancer
      - Breast Cancer
    - Conclusion
    - References
  - Chapter 36i. Perspectives in Imaging: Present and Future Prospects of Clinical Molecular Imaging
    David Piwnica-Worms.
    - Clinical Molecular Imaging Today: PET and SPECT
      - Enzymes
      - Receptors
      - Transporters
    - On the Horizon: Imaging Gene Expression in vivo with Reporter Genes
    - On the Horizon: Clinical Molecular Imaging with Optical and MRI
    - Summary
    - Acknowledgments
    - References
  - Chapter 37. Interventional Radiology for the Cancer Patient
    Marshall Hicks, Michael Wallace, and Sanjay Gupta.
    - Intra-arterial Therapy
      - Infusion Therapy
      - Embolization
      - Chemoembolization
      - Hepatic Neoplasms: Hepatocellular Carcinoma
      - Hepatic Metastases
    - Biopsy
      - Thorax
      - Abdomen
      - Lymph Nodes
      - Musculoskeletal Biopsy
    - Intratumoral Gene Therapy
    - Mechanical Devices
      - Vena Cava Filters
      - Metallic Stents
      - Venous Stenosis
      - Stomach and Proximal Small Bowel
      - Colon Stents
      - Biliary Stents
      - Complications
      - Transjugular Intrahepatic Portosystemic Shunts
    - References
Part IV Therapeutic Modalities
- Section 8: Surgical Oncology
  - Chapter 38. Principles of Surgical Oncology
    Raphael E. Pollock and Donald L. Morton.
    - Historical Considerations
    - The Contemporary Role of Surgical Oncology
    - Combined Modality Therapy
    - Surgical Components of Cancer Management
      - Prevention
      - Biopsy and Diagnosis of Tumors
      - Staging
      - Patterns of Tumor Spread
      - Preoperative Preparation
      - Operative Considerations
      - Types of Cancer Operations
    - Special Situations
      - Vascular Access
      - Emerging Technologies
      - Surgical Oncology in the Future
    - References
- Section 9: Radiation Oncology
  - Chapter 39. Principles of Radiation Oncology
    Arno J. Mundt, John C. Roeske, Theodore D. Chung, and Ralph R. Weichselbaum.
    - Physical Basis of Radiation Therapy
      - Types of Radiation
      - Radiation Absorbed Dose
    - Treatment Planning and Delivery
      - External Beam Therapy
      - Brachytherapy
    - Biologic Basis of Radiation Therapy
      - Cellular Response to Radiation
      - Radiation Survival Analysis
      - Models of Radiation Survival Curve Analysis
      - Classic Aspects of DNA Repair in Radiotherapy
      - Cell Cycle Checkpoints, Integration of Signalling, and DNA Repair
      - Fractionation
      - Modifiers of the Radiation Response
      - Growth Factor and Cytokine Induction Following Radiation Exposure Growth and Regeneration Kinetics
      - Induction of Apoptosis
      - Dose Response and the Therapeutic Ratio
      - Gene Therapy and Radiation Therapy
      - Antiangiogenic Therapy Combined with Radiation Therapy
      - Clinical Radiation Oncology
      - Prophylactic Therapy
      - Palliative Therapy
      - Radiation Sequelae
    - Future Directions
    - References
  - Chapter 40. Photodynamic Therapy of Cancer
    Tayyaba Hasan, Bernhard Ortel, Anne C.E. Moor, and Brian W. Pogue.
    - History
    - Overview
    - Basics of Light and PDT-Related Photochemistry
    - Photosensitizers
      - Anionic Lipophilic Photosensitizers
      - Cationic Photosensitizers
      - δ-Aminolevulinic Acid-Based PDT
    - Photosensitizer Transport and Distribution
    - Biologic Mechanisms of PDT
      - Cellular Mechanisms
      - In Vivo Mechanisms
    - Photodynamic Therapy Dosimetry
      - In Vivo Light Dosimetry
      - In Vivo Photosensitizer Dosimetry
      - In Vivo Oxygen Dosimetry
    - Photodynamic Therapy with Targeted Molecular Delivery Systems
      - Photoimmunotargeting
      - Targeting with LDLs
    - Perspectives
    - Acknowledgments
    - References
  - Chapter 41. Hyperthermia
    Mark W. Dewhirst, Ellen Jones, Thaddeus Samulski, Zeljko Vujaskovic, Chuan Li, and Leonard Prosnitz.
    - The Biology of Hyperthermia
      - Definition of Hyperthermia
      - The Arrhenius Relationship and Thermal Isoeffect Dose
      - Modifiers of Thermal Cytotoxicity
      - Mechanisms of Hyperthermic Cytotoxicity
    - Hyperthermia and Physiology
      - Physiologic Response to Hyperthermia
      - Taking Advantage of Physiological Response to Hyperthermia
      - Normal Tissue Damage from Hyperthermia
    - Physiologic Approaches to Enhance Thermal Cytotoxicity
      - pH Modification
      - Blood Flow Manipulation
      - Hyperthermia and Metastases
      - Radiation and Hyperthermia
    - Hyperthermia and Chemotherapy
      - Rationale for Using Hyperthermia with Chemotherapy
      - Factors to Consider When Combining Hyperthermia with Chemotherapy
      - Hyperthermia and Gene Therapy
    - Hyperthermia Physics
      - Electromagnetic Heating
      - Ultrasound Heating
      - Measurement of Temperatures During Hyperthermia
      - Noninvasive Thermometry
    - Clinical Hyperthermia
      - General Considerations
      - Relationship Between Thermal Dose and Outcome
      - Clinical Trials Overview
      - Summary of Clinical Trials
    - Acknowledgments
    - References
- Section 10: Medical Oncology
  - Chapter 42. Principles of Medical Oncology
    James F. Holland, Emil Frei, III, Donald W. Kufe, and Robert C. Bast, Jr.
    - Medical Oncologist's Role
    - Clinical Responsibilities
    - Cancer Prevention
    - Clinical Research
    - Fundamental Science, Clinical Science, and Medical Art
    - Chemotherapy Trials
    - Adjuvant and Neoadjuvant Chemotherapy
    - Surrogate End Points
    - Palliative Therapy
    - Laws of Therapeutics
    - Truth Telling
    - Resuscitation
    - Burnout
    - Nomenclature: Systeme Internationale (SI) Units
    - Summary
    - References
- Section 11: Chemotherapy
  - Chapter 43. Cytokinetics
    Chau Dang, Teresa A. Gilewski, Antonella Surbone, and Larry Norton.
    - Cell Proliferation
      - Mitotic Cycle: Percentage of Labeled Mitoses Curves
      - Cell Cycle Phases and DNA Content
      - Flow Cytometry
      - Mitotic Compartments
      - Cytokinetics and Biologic Diversity
    - Growth Curve Analysis
      - Skipper-Schabel-Wilcox Model
      - Delbruck-Luria Model
      - Goldie-Coldman Model
      - Implications of Relative Drug Resistance
      - Gompertzian Model
      - Speer-Retsky Model
      - Norton-Simon Model
      - Mitotoxicity Hypothesis
    - Conclusion
    - References
  - Chapter 44. Principles of Dose, Schedule, and Combination Therapy
    Emil Frei, III and Joseph Paul Eder.
    - Dose
      - Factors Influencing the Dose Effect
      - Clinical Trials and the Dose Effect
      - Adjuvant Chemotherapy
      - Dose Effect-A Summary
    - Schedule of Drug Administration
      - Schedule Effects of Individual Drugs by Class
      - Schedule Effects of Individual Agents
      - General Use of Intermittent Dosing
      - Continuous Low-dose Administration
    - Combination Chemotherapy
      - The Rationale for Combination Chemotherapy
      - Combination Chemotherapy in the Clinic
      - Implications of Drug Resistance
      - Implications and Reversal of Drug Resistance
      - Molecular Biology/Targeted Therapy- Implications for Dose and Schedule
      - Experimental Models of Combination Therapy
    - References
  - Chapter 45. Preclinical and Early Clinical Development of New Anticancer Agents
    Daniel D. Von Hoff and Axel-R. Hanauske.
    - Evolution of the Discovery Process
      - Clinical Observation in the Discovery Process
      - Histocytotoxic Effects and Physiologic Observations
      - Early and Continuing Role of the National Cancer Institute Drug Discovery Program in the Drug Discovery Process
      - Targeted (or Mechanistically Based) Drug Discovery and Evaluation
      - Sources of Compounds to Evaluate Against Targets
    - Preparation of Agents for Clinical Trials
      - Formulation
      - Development of an Assay for a Pharmacodynamic End Point (Surrogate Markers)
      - Animal Pharmacology
      - Animal Toxicology Studies
      - Preparation of an IND Application
    - Early Clinical Trials
      - Phase I Clinical Trial
      - Phase I Trial in Patients versus Normal Volunteers
      - Selection of a Schedule and a Route for the Phase I Trial
      - Calculation of the Starting Dose for the Phase I Trial
      - Methods for Dose Escalation
      - Definitions of MTD and DLTs
      - Selection Criteria for Patients for Phase I Trials
      - Are Phase I Clinical Trials Therapeutic?
      - Combination of Agents in Phase I Trials
      - Issues Regarding Phase I Trials in General
      - Future Technologies Likely to Impact on Phase I Trials
    - References
  - Chapter 46. Pharmacology
    Mark J. Ratain and William K. Plunkett, Jr.
    - General Mechanisms of Drug Action
      - Membrane Transport
      - Intracellular Activation
      - Drug Targets
      - Repair of Drug-Induced Injury
    - Principles of Pharmacokinetics
      - Definitions
      - Linear Pharmacokinetic Models
      - Nonlinear Pharmacokinetic Models
      - Interpatient Pharmacokinetic Variability
      - Intrapatient Pharmacokinetic Variability
      - Drug-Drug Interactions
    - Principles of Pharmacodynamics
      - Definitions
      - General Pharmacodynamic Principles
      - Pharmacodynamic Modeling of Cancer Chemotherapy
      - The Future Role of Anticancer Pharmacodynamics
    - References
  - Chapter 47. Regional Chemotherapy
    Maurie Markman.
    - Pharmacokinetic Rationale for Regional Chemotherapy
    - Mathematical Model Describing Regional Anticancer Drug Delivery
      - Clinical Implications of the Pharmacokinetic Model
    - Theoretical Concerns with Regional Antineoplastic Drug Therapy
    - Practical Issues Associated with Regional Anticancer Drug Delivery
    - Clinical Examples of Regional Antineoplastic Drug Delivery
      - Intrathecal Therapy for the Prevention and Treatment of Meningeal Leukemia
      - Intraperitoneal Chemotherapy in the Management of Ovarian Cancer
      - Intrahepatic Arterial Therapy for Colon Cancer Metastatic to the Liver
      - Intravesical Therapy of Localized Bladder Cancer
    - Conclusion
    - References
  - Chapter 48. Drug Resistance and Its Clinical Circumvention
    Jeffrey Moscow, Charles S. Morrow, and Kenneth H. Cowan.
    - General Mechanisms of Drug Resistance
      - Decreased Drug Accumulation
      - Altered Drug Metabolism
      - Increased Repair or Cellular Tolerance or Drug-Induced Damage
      - Altered Drug Targets
      - Altered Gene Expression
    - Resistance to Multiple Drugs
      - Classic (P-Glycoprotein-Dependent) MDR
      - Multidrug Resistance Protein Family
      - MDR Associated with Topoisomerase Poisons
      - MDR Associated with Altered Expression of Drug-Metabolizing Enzymes and Drug-Conjugate Export Pumps
      - Emergence of Refractory Tumors Associated with Multiple Resistance Mechanisms
      - Resistance to Anticancer Genotoxic Treatments Related to Suppression of Apoptotic Pathways
    - Resistance Factors Unique to Tumor Cells In Vivo: Host-Tumor-Drug Interactions
    - Potential Clinical Application of Strategies to Avert or Overcome Drug Resistance
      - P-Glycoprotein- and MRP1-Mediated Resistance
      - Topoisomerase II Poisons
      - Resistance to Free Radical-Mediated Drug Cytotoxicity
      - Alkylating Agents and Platinum Compounds
      - Antimetabolites
    - Conclusion and Future Directions
    - References
- Section 12: Chemotherapeutic Agents
  - Chapter 49. Folate Antagonists
    Barton A. Kamen, Peter D. Cole, and Joseph R. Bertino.
    - Historical Overview
    - Mechanism of Action
    - Pharmacokinetics of MTX
      - Absorption
      - Distribution
      - Metabolism
      - Biliary Excretion
    - Inadvertent Drug Interactions with MTX
    - Clinical Application
      - Clinical Dosage Schedules
      - Clinical Uses of MTX in the Treatment of Neoplastic Disease
    - Adverse Effects
      - Hematologic Toxicity
      - Gastrointestinal Toxicity
      - Renal Toxicity
      - Hepatotoxicity
      - Central Nervous System Toxicity
      - Pulmonary Toxicity
      - Skin Toxicity
      - Teratogenic and Mutagenic Effects
      - Miscellaneous Toxicity
    - Resistance to Antifolates
      - Intrinsic Resistance to MTX
      - Acquired Resistance to MTX
    - Strategies to Overcome Resistance to MTX Using New (or Older) AntiFols
      - Aminopterin
      - Newer Inhibitors of DHFR
      - Inhibitors of Other Folate-Dependent Enzymes
    - References
  - Chapter 50. Pyrimidine and Purine Antimetabolites
    Giuseppe Pizzorno, Robert B. Diasio, and Yung-Chi Cheng.
    - Pyrimidine Analogs
      - 5-Fluorouracil
      - Cytosine Arabinoside
      - 5-Azacytidine
      - Gemcitabine
    - Purine Analogs
      - Deoxycoformycin
      - Fludarabine
      - Cladribine
      - Hydroxyurea
    - References
  - Chapter 51. Alkylating Agents and Platinum Antitumor Compounds
    Michael Colvin.
    - Alkylating Agents
      - Chemistry of the Alkylating Agents
      - Types of Alkylating Agents
      - Nitrosoureas
      - Triazenes, Hydrazines, and Related Compounds
      - Decomposition and Metabolism
      - Mechanism of Cytotoxicity
      - Cellular Resistance to Alkylating Agents
      - Clinical Pharmacology
      - Toxicities
      - Cellular and Molecular Pharmacology
      - Mechanisms of Cellular Resistance to Platinum Agents
      - Toxicities
    - References
  - Chapter 52. Anthracyclines and DNA Intercalators/Epipodophyllotoxins/ Camptothecins/DNA Topoisomerases
    Eric H. Rubin and William N. Hait.
    - Topoisomerase Biology
    - How Drugs “Poison” Topoisomerases
    - Cellular Response to Topoisomerase-Mediated DNA Damage
    - Mechanisms of Resistance to Topoisomerase Targeting
    - Intercalating Drugs that Target Topoisomerases
      - Anthracyclines
      - Anthracenediones
    - Nonintercalating Topoisomerase-Targeting Drugs
      - Epipodophyllotoxins
    - References
  - Chapter 53. Microtubule-Targeting Natural Products
    Eric Rowinsky.
    - Microtubules as Strategic Targets Against Cancer
    - The Vinca Alkaloids
      - Mechanism of Action
      - Mechanisms of Resistance
      - Clinical Indications
      - Clinical Pharmacology
      - Toxicity
      - Administration, Dose, and Schedule
    - The Taxanes
      - Clinical Indications
      - Mechanisms of Action
      - Mechanisms of Resistance
      - Clinical Pharmacology
      - Administration, Dose, and Schedule
    - Novel Compounds Targeting Microtubules and Related Organelles
    - References
  - Chapter 54. Small-Molecule Inhibitors of Protein Kinases in the Treatment of Human Cancer
    Michael C. Heinrich, Charles D. Blanke, Christopher L. Corless, and Brian J. Druker.
    - Strategies to Inhibit Tyrosine Kinases
    - Tyrosine Kinase Inhibitors: Targeting Considerations
      - BCR-ABL as a Therapeutic Target
      - Preclinical Development of Imatinib
      - Clinical Studies of Imatinib in CML
      - Mechanisms of Relapse/Resistance to Imatinib
    - KIT as a Therapeutic Target
      - GISTs as a Model Disease for a KIT TKI
      - Assessing GIST Response to Imatinib Therapy
      - Other KIT-Positive Malignancies
    - PDGF Receptors as Therapeutic Targets
      - PDGFRB as a Therapeutic Target
      - PDGFRA as a Therapeutic Target
      - Additional PDGFR Targets
    - ARG (Abelson-Related Gene) as a Therapeutic Target
    - Toxicity of TKIs
    - Considerations in Clinical Trial Design for Tyrosine Kinase Inhibitors
    - References
- Section 13: Biotherapeutics
  - Chapter 55. Asparaginase
    Joanne Kurtzberg, David Yousem, and Norman Beauchamp, Jr.
    - Mechanism of Action, Chemistry, and In Vitro Activity
      - Clinical History
      - Toxicity
      - Hypersensitivity
      - Asparaginase Pharmacology
      - Drug Interactions
    - Conclusions
    - References
  - Chapter 56. Interferons
    Ernest C. Borden.
    - Molecules: Their Induction, Receptors, and Gene Regulation
      - Interferon Induction
      - Receptors
      - Signal Transduction
      - Induced Genes and Antitumor Actions
    - Mechanisms of Antitumor Action
      - Antiproliferative, Apoptotic, and Differentiative Effects
      - Immune Effector Cells
    - Angiogenesis Inhibition
    - Antitumor Effects in Humans
      - Hematologic Malignancies
      - Solid Tumors
      - Side Effects
    - Perspective
    - References
  - Chapter 57. Cytokines: Biology and Applications in Cancer Medicine
    Suhendan Ekmekcioglu and Elizabeth A. Grimm.
    - Interleukin-2
      - Biology and Preclinical Rationale
      - Clinical Applications
      - IL-2 Toxicities
    - Interleukin-12
      - Biology and Preclinical Rationale
      - Clinical Applications
    - Tumor Necrosis Factor-α
      - Biology and Preclinical Rationale
      - Clinical Applications
    - Interleukin-1
      - Biology and Preclinical Rationale
      - Clinical Trials
    - Interleukin-6
      - Biology and Preclinical Rationale
      - Clinical Trials
    - Interleukin-4
      - Biology and Preclinical Rationale
      - IL-4 Clinical Trials
    - Colony-Stimulating Factors
    - Cytokines Considered for Clinical Application or in Early Trials
      - Interleukin-10
      - Interleukin-13
      - Interleukin-15
      - Interleukin-17
      - Interleukin-18
      - Interleukin-19
      - Interleukin-20
      - Interleukin-22
      - Interleukin-24
      - Interleukin-25
    - Conclusions
    - Acknowledgments
    - References
  - Chapter 58. Hematopoietic Growth Factors
    Razelle Kurzrock.
    - Hematopoiesis and the role of growth factors
    - Erythropoietin
      - Major production sites of EPO
      - EPO receptor
      - Biologic activities of EPO
      - EPO and human disease
      - EPO in the clinic
    - Granulocyte-macrophage colony-stimulating factor
      - Structure of GM-CSF
      - Major sites of production of GM-CSF GM-CSF can be synthesized by a variety of cell types in response to specific activating signals
      - GM-CSF receptor
      - Major biologic activities of GM-CSF
      - GM-CSF in human illness
      - Clinical indications for GM-CSF
    - Granulocyte colony-stimulating factor
      - Forms of G-CSF
      - G-CSF receptor
      - Biologic activities of G-CSF
      - G-CSF in human illness
      - Clinical indications for G-CSF
    - Macrophage colony-stimulating factor
      - Structure of M-CSF
      - M-CSF receptor
      - Biologic activities of M-CSF
      - M-CSF in human illness
      - M-CSF in the clinic
    - Stem cell factor
      - SCF structure
      - c-kit Receptor
      - SCF production
      - Biologic activities of SCF
      - SCF and c-kit in human disease
      - SCF in the clinic
    - Thrombopoietin
      - TPO structure
      - TPO production
      - Biologic properties of TPO
      - TPO and human disease
      - TPO in the clinic
    - Interleukin-1
      - IL-1 family
      - IL-1 receptors
      - ICE
      - Production of IL-1 family members
      - Biologic effects of IL-1
      - IL-1 and hematopoiesis
      - IL-1 and human disease
      - IL-1 in the clinic
    - Interleukin-2
      - Structure
      - Production of IL-2
      - IL-2 receptors
      - Biologic activities of IL-2
    - Interleukin-3
      - Structure of IL-3
      - IL-3 receptor
      - IL-3 production
      - Biologic properties of IL-3
      - IL-3 in human disease
      - IL-3 in the clinic
    - Interleukin-4 and Interleukin-13
      - IL-4 and IL-13 receptors
      - Production of IL-4 and IL-13
      - Biologic activities of IL-4 and IL-13
      - IL-4 and IL-13 in human disease
      - Clinical trials of IL-4
    - Interleukin-5
      - IL-5 structure
      - Production of IL-5
      - IL-5 receptor
      - Biologic activities of IL-5
      - IL-5 and human illness
    - Interleukin 6
      - Structure of IL-6
      - Sources of IL-6
      - IL-6 receptor
      - Biologic activities of IL-6
      - IL-6 and human illness
      - IL-6 in the clinic
    - Interleukin-7
      - IL-7 receptor
      - Biologic activities of IL-7/IL-7 receptor
      - IL-7 and human illness
    - Interleukin-8
      - Structure of IL-8
      - Major production sites of IL-8
      - IL-8 receptor
      - Biologic activity of IL-8
      - IL-8 in human illness
    - Interleukin-9
      - Structure of IL-9
      - Biologic activities of IL-9
      - IL-9 in human disease
      - Interleukin-10
      - Major production sites of IL-10
      - Biologic activities of IL-10
      - IL-10 and human illness
    - Interleukin-11
      - Structure of IL-11
      - Production sites of IL-11
      - IL-11 receptor
      - Biologic activities of IL-11
      - IL-11 in human illness
      - Clinical use of IL-11
      - Interleukin-12
      - Structure of IL-12
      - Production of IL-12
      - IL-12 receptor
      - Biologic activities of IL-12 and role in illness
      - IL-12 in the clinic
    - Interleukin-15
      - IL-15 production
      - IL-15 receptors
      - Biologic activities of IL-15
      - IL-15 and human disease
    - Interleukin-16
      - IL-16 structure
      - IL-16 production
      - IL-16 receptor
      - Biologic activities of IL-16
      - IL-16 in human disease
    - Interleukin-17
      - IL-17 structure
      - IL-17 production
      - IL-17 receptor
      - Biologic activities of IL-17
      - IL-17 in human disease
    - Interleukin-18
      - IL-18 receptor
      - Biologic activities of IL-18
    - Other Hematopoietic Growth Factors
      - FLT-3 Ligand
    - Use of hematopoietic growth factors after chemotherapy
      - Hematopoietic growth factors and standard-dose chemotherapy of solid tumors
      - Hematopoietic growth factors and high-dose chemotherapy in solid tumors
      - Use of hematopoietic growth factors in febrile and afebrile neutropenic patients
      - Hematopoietic growth factors in leukemic patients
      - Colony-stimulating factor regimens (timing and duration)
      - Non-myeloid growth factors
    - Hematopoietic growth factors in the transplantation setting
      - G-CSF
      - GM-CSF
      - M-CSF
    - Thrombopoietic agents in the clinic: an overview
    - Hematopoietic growth factors in bone marrow failure states
      - Hematopoietic growth factors in myelodysplastic syndrome
      - Aplastic anemia
      - Severe chronic neutropenia
    - Future perspectives
    - References
  - Chapter 59. Monoclonal Serotherapy
    Robert C. Bast, Jr, Christina A. Kousparou, Agamemnon A. Epenetos, Michael R. Zalutsky, Robert J. Kreitman, Edward A. Sausville, and Arthur E. Frankel.
    - Therapy with Unmodified Monoclonal Antibodies
      - Treatment in Vivo
    - Barriers to Successful Serotherapy
      - Antigen Specificity
      - Effective Delivery of Antibody to Tumor Cells
      - Heterogeneity of Antigen Expression
      - Immune Response to Foreign Immunoglobulin
      - Potency of Effector Mechanisms
    - Elimination of Malignant Cells from Bone Marrow Ex Vivo
    - Therapy with Drug-Monoclonal Antibody Conjugates
      - Gemtuzumab Ozogamicin
    - Radioimmunotherapy of Cancer
      - Choice of Radioisotope
      - Chelators
      - Radioimmunoscintigraphy and Radioimmunoguided Surgery
      - RIT in Hematologic Malignancies
      - RIT in Solid Tumors
      - Strategies for Improved RIT
    - Targeted Toxins
      - Efficacy
      - Toxicities
      - Pharmacology
    - Conclusions
    - References
  - Chapter 60. Vaccines and Immunostimulants
    Jeffrey Schlom and Scott I. Abrams.
    - Targets for Vaccine Therapy
      - Tumor-Specific Antigens
      - Tumor-Associated Antigens
    - Issues in Cancer Vaccine Development
    - Problem Areas in Immunotherapy
    - Types of Vaccines
      - Whole-Tumor-Cell Vaccines
      - Autologous Whole-Tumor-Cell Vaccines
      - Allogeneic Whole-Tumor-Cell Vaccines
      - Direct Injection of Cytokine Genes or Costimulatory Molecule Genes into Tumor
      - Proteins
      - Peptides
      - Agonist Peptides
      - Antiidiotypes
      - Vectors
      - Replication-Competent Vectors
      - Replication-Defective Viral Vectors
      - Bacterial Vectors
      - DNA Vectors
      - RNA Virus Vectors
      - Dendritic Cell Vaccines
      - Fusion Proteins and Immunoglobulins
    - Diversified Prime and Boost Immunization Strategies
    - Immunostimulants/Cytokines
    - T-Cell Costimulation
    - Adoptive Transfer
    - Vaccine Clinical Trials
      - Melanoma
      - Gastrointestinal Carcinoma
      - Breast Cancer
      - Prostate Cancer
      - Lymphoma
      - Other Tumor Types
      - Combination Therapy
    - Conclusion
    - Acknowledgments
    - References
- Section 14: Endocrine Therapy
  - Chapter 61. Hypothalamic and Other Peptide Hormones
    Andrew V. Schally and Ana Maria Comaru-Schally.
    - Analogs of Peptide Hormones
      - Hypothalamo-Hypophysial Relationship, Hypothalamic Hormones, and Other Peptides
    - Agonists of LHRH
      - Early Studies and the Basis of Oncologic Applications
      - Development of Sustained-Delivery Systems
      - Current Uses of LHRH Agonists
      - Pharmacokinetics and Metabolism
      - Side Effects and Toxicology
    - LHRH Antagonists
      - Current Clinical Status of LHRH Antagonists
      - LHRH Analogs Carrying Cytotoxic Radicals
    - Mode of Action of LHRH Analogs
      - Pituitary-Gonadal Axis
      - Direct Effects
      - Receptors for LHRH in Various Tumors
      - Inhibition of Growth of Tumor Cell Lines
    - Somatostatin Analogs
      - Side Effects
      - Mechanisms of Antitumoral Action of Somatostatin Analogs
      - Receptors for Somatostatin
      - Localization of Tumors and Metastases by Scintigraphy with Radiolabeled Somatostatin Analogs
      - Use of Radiolabeled Somatostatin Analogs for Local Tumor Therapy
      - Cytotoxic Analogs of Somatostatin
    - Antagonists of Bombesin and Gastrin-Releasing Peptide
      - Receptors for Bombesin/Gastrin Releasing Peptide
      - Antagonists of Bombesin/Gastrin Releasing Peptide
      - Cytotoxic Analogs of Bombesin
    - Antagonists of Growth Hormone-Releasing Hormone
      - Ghrelin
    - Treatment of Various Tumors with Peptide Analogs
      - Prostate Cancer
      - Breast Cancer
      - Epithelial Ovarian Cancer
      - Endometrial Carcinoma
      - Exocrine Pancreatic Cancer
      - Colorectal Cancer
      - Gastric Cancer
      - Brain Tumors
      - Lung Cancer
      - Bone Cancers
      - Renal Cancer
      - Hepatocellular Carcinoma
    - Tumors Producing Hypothalamic Hormones
    - References
  - Chapter 62. Corticosteroids
    Lorraine I. McKay and John A. Cidlowski.
    - Hormones of the Adrenal Cortex
      - Adrenal Anatomy
      - Secreted Steroids
      - Biosynthetic Pathways
    - Control of Corticosteroid Secretion
      - Glucocorticoids
      - Mineralocorticoids
    - Pharmacokinetics of Corticosteroids
      - Rate of Secretion
      - Metabolism
      - Plasma Clearance
      - Excretion
      - Transport in Blood
    - Steroid Synthesis Inhibitors
    - Pharmaceutical Derivatives
    - Physiologic and Pharmacologic Effects of Corticosteroids
      - Intermediary Metabolism
      - Electrolyte and Water Balance
      - Endocrine System
      - Cardiovascular System
      - Musculoskeletal System
      - Central Nervous System
      - Hematologic Effects
      - Antiinflammatory Effects
      - Immune System
      - Other Effects
    - Corticosteroids in the Treatment of Neoplasms
      - Neoplasms Treated with Corticosteroids
      - Symptomatic Uses of Corticosteroids
    - References
  - Chapter 63. Estrogens and Antiestrogens
    Craig V Jordan.
    - Tamoxifen
      - General Pharmacology in the Laboratory
      - Mode of Action in Breast Cancer
      - Clinical Pharmacology
      - Use in Advanced Breast Cancer
      - Use as Adjuvant Therapy
      - Chemotherapy Plus Tamoxifen
      - Tamoxifen Alone
      - Toxicologic Considerations in Postmenopausal Women
      - Ophthalmic Effects
      - Antiestrogenic Effects
      - Estrogenic Effects
      - Tamoxifen in the Prevention of Breast Cancer
    - New Agents
      - Toremifene
      - Pure Antiestrogens
      - Raloxifene
    - Conclusion
    - References
  - Chapter 64. Aromatase Inhibitors
    Aman U. Buzdar and Harold A. Harvey.
    - Biology of Aromatase
      - Gene Structure and Regulation
      - Sites of Estrogen Biosynthesis
    - Historical Development of Aromatase Inhibitors
      - Clinical Efficacy
      - Side Effects
    - Development of Improved Aromatase Inhibitors
    - Classification
      - Mechanism-Based (Suicide) Inhibitors
      - Exemestane
      - Competitive Inhibitors
      - Second Line Studies
      - First-Line Studies
      - Neoadjuvant Therapy with Aromatase Inhibitors
      - Adjuvant Therapy with Aromatase Inhibitors
    - Selection of Patients for Aromatase Inhibition Therapy
      - Postmenopausal Women
      - Premenopausal Patients
      - Male Breast Cancer
    - Future Perspectives in the Clinical Development of Aromatase Inhibitors
      - Chemoprevention
      - Combination versus Sequential Therapy
      - Hormonal Resistance and Breast Cancer Biology
    - Summary
    - References
  - Chapter 65. Progestins
    Kenneth S. McCarty, Jr, Mark Nichols, and Kenneth S. McCarty, Sr.
    - Physiology
    - Pharmacology
      - Basic Mechanism of PgR Ligand-Dependent Transcription
    - Clinical Observations on Progestin Receptor and Target Tissue Responses to Progestins
      - The Uterus
      - The Breast
      - The Ovary
      - Other Tissues
    - Conclusion
    - References
  - Chapter 66. Androgen Deprivation Strategies in the Treatment of Advanced Prostate Cancer
    Samuel R. Denmeade and John T. Isaacs.
    - Cellular Organization of the Normal Prostate
    - Definition of Androgen Responsiveness on a Cellular Basis
    - Mechanism of Androgen Action
    - Overview of Regulation of Systemic Androgen Levels
    - Pharmacologic Approaches to Lower Circulating Androgen
      - LHRH Analogs
      - Antiandrogens
      - Estrogens
      - Androgen Synthesis-Inhibiting Agents
      - 5α-Reductase Inhibitors
    - Androgen Deprivation Strategies for the Treatment of Recurrent and Metastatic Prostate Cancer
      - LHRH Agonists as Monotherapy
      - Combined Androgen Blockade
    - Alternative Strategies for Androgen Deprivation
      - Revisiting Estrogen as Monotherapy for Prostate Cancer
      - Non-Steroidal Antiandrogens as Monotherapy
      - Intermittent Androgen Suppression
      - Second-Line Hormonal Therapy
      - PC-SPES
      - Timing of Androgen Deprivation Therapy
      - Neoadjuvant and Adjuvant Hormone Therapy
    - Conclusion
    - References
- Section 15: Gene Therapy
  - Chapter 67. Cancer Gene Therapy
    Sunil J. Advani, Ralph R. Weichselbaum, and Donald W. Kufe.
    - Gene Delivery Systems
      - Retroviruses
      - Adenoviruses
      - Herpes Simplex Viruses
      - Adeno-associated Virus
      - Nonviral Gene Delivery
    - Therapeutic Genes
      - Virus-directed Enzyme/Prodrug Therapy
      - Gene Therapy Directed at Cell-Cycle Control and Apoptosis
      - Downregulation of Genes Involved in Tumor Progression
      - Immunomodulatory Genes
    - Selective Gene Expression
      - Tumor-selective Retroviruses
      - Tumor-selective Adenoviruses
      - Tumor-selective Adeno-associated Virus
      - Tumor-selective Promoters/Enhancers
      - Inducible Promoters
    - Viral Oncolysis
      - Oncolytic Adenovirus
      - Oncolytic Herpes Simplex Virus-1
      - Oncolytic Reovirus
    - References
- Section 16: Bone Marrow Transplantation
  - Chapter 68. Autologous Bone Marrow and Stem Cell Transplantation
    William P. Peters, Roger Dansey, and Roy D. Baynes.
    - Rationale and Requirements for Autologous Hematopoietic Stem Cell Transplantation
    - Principles
    - Dose Intensity
    - Combination Chemotherapy
    - Volume of Disease
    - Procedure
      - Selection of Patient
      - Marrow Harvesting Technique and Complications
      - Peripheral Blood Stem Cell and Progenitor Cell Collection
      - Hematopoietic Stem Cell Processing
      - Cytoreductive Therapy: Administration and Supportive Care
    - Specific Diseases
      - Acute Myelocytic Leukemia
      - Acute Lymphoblastic Leukemia
      - Non-Hodgkin Lymphoma
      - Hodgkin Disease
      - Breast Cancer
      - Small-Cell Lung Cancer
      - Ovarian Cancer
      - Melanoma and Colon Cancer
      - Myeloma
      - Chronic Myeloid Leukemia
      - Gliomas
      - Testicular Cancer
      - Neuroblastoma
      - Ewing and Other Sarcomata
    - Autoimmune Diseases
    - Toxicities
      - Myelosuppression, Colony-Stimulating Factors, and Peripheral Stem Cells
    - Immune Function Posttransplant
    - Organ Toxicity
    - Future Directions
    - References
  - Chapter 69. Hematopoietic Cellular Transplantation
    Richard Champlin.
    - Hematopoietic Transplantation as Treatment for Malignancies
    - Donor Selection
    - Engraftment of Allogeneic Hematopoietic Transplants
    - Cell Sources for Hematopoietic Transplantation
    - Autologous Transplantation, Tumor Cell Contamination, and Purging
    - Selection of Autologous or Allogeneic Transplantation
    - Complications of Hematopoietic Transplantation
      - Graft Rejection and Graft Failure
      - Graft versus Host Disease (GVHD)
      - Regimen-Related Toxicity
      - Hematologic complications
      - Immunodeficiency and Infections
      - Late effects
    - Indications for Hematopoietic Transplantation
      - Acute Myeloid Leukemia (AML)
      - Myelodysplastic Syndromes
      - Acute Lymphoblastic Leukemia (ALL)
      - Chronic Myeloid Leukemia (CML)
      - Chronic Lymphocytic Leukemia (CLL)
      - Non-Hodgkin Lymphoma
      - Hodgkin Disease
      - Multiple Myeloma
      - Solid Tumors
      - Nonmalignant Indications
    - Future Directions
    - References
Part V Multidisciplinary Management
- Section 17: Psycho-Oncology
  - Chapter 70. Psycho-Oncology
    Jimmie C. Holland and Jane Gooen-Piels.
    - Historical Perspective
    - Hearing the Diagnosis
    - Factors in Adaptation to Cancer
      - Society-Derived Factors
      - Patient-Derived Factors
      - Cancer-Derived Factors
    - Psychosocial Problems
      - Adaptation to Active Treatment
      - Adaptation to Palliative Care
      - Adaptation to Being a Survivor
      - Adaptation to Increased Genetic Risk of Cancer
    - Guidelines for Recognition of Psychosocial Distress
    - Psychiatric Disorders
      - Anxiety Disorders
      - Depression
      - Suicide and Cancer
      - Delirium
      - Psychiatric and Psychosocial Interventions
      - Blurring of Conventional Psychosocial and Behavioral Interventions with Alternative/ Complementary Therapies
      - Quality-of-Life Assessment
      - Family Issues and Bereavement
      - Grief in Surviving Family Members
      - Stress and Burnout in Oncology Staff
    - Summary
    - References
- Section 18: Oncology Nursing
  - Chapter 71. Principles of Oncology Nursing
    Paula Trahan Rieger and Connie Henke Yarbro.
    - Oncology Nursing as a Specialty
      - Certification
      - Oncology Nursing Education
      - Oncology Nursing Research
      - Health Policy
    - Role of the Oncology Nurse
      - Patient Assessment
      - Patient Education
      - Coordination of Care
      - Direct Patient Care
      - Symptom Management
      - Supportive Care
    - Survivorship
    - Advanced Practice in Oncology Nursing
    - Nursing Shortage
    - Summary
    - References
- Section 19: Cancer Rehabilitation Medicine
  - Chapter 72. Principles of Cancer Rehabilitation Medicine
    Kristjan T. Ragnarsson and David C. Thomas.
    - Application of Rehabilitation Concepts
    - The Cancer Rehabilitation and Adaptation Team
    - Functional Assessment
    - The Rehabilitation Process
    - Cancer of the Brain
    - Cancer of the Spine
      - Clinical Presentation
      - Treatment
    - Cancer of the Head and Neck
    - Cancer of the Lung
    - Cancer of the Breast
    - Cancer of the Gastrointestinal Tract
      - Colostomy
      - Ileostomy
    - Cancer of the Genitourinary System
      - Genital Cancer
      - Sexual Rehabilitation
    - Cancer of the Limbs
      - Preoperative Rehabilitation
      - Limb Amputation
      - Postoperative Exercise Program
      - Prescription of an Artificial Limb
      - Prosthetic Fitting and Training
      - Limb-Sparing Surgical Reconstruction
    - Conclusion
    - References
- Section 20: Multidisciplinary Management
  - Chapter 73. Principles of Multidisciplinary Management
    James F. Holland, Emil Frei, III, Donald W. Kufe, Robert C. Bast, Jr, Raphael E. Pollock, and Ralph R. Weichselbaum.
    - The Primary Physician
    - The Radiologist
    - The Pathologist
    - The Surgical Oncologist
    - The Anesthesiologist
    - The Medical Oncologist
    - The Radiation Oncologist
    - The Gynecologic Oncologist
    - The Neurosurgeon
    - The Pediatric Oncologist
    - The Psycho-oncologist
    - The Rehabilitation Specialist
    - The Oncology Nurse
    - The Oncology Pharmacist
    - Nonmedical Professionals
    - Family Members
  - Chapter 74. Cancer and Pregnancy
    Richard L. Theriault, Karin M.E.H. Gwyn, and Gabriel N. Hortobagyi.
    - Cancer and Pregnancy Epidemiology
    - Diagnosis and Staging
    - Cancer Treatment During Pregnancy
      - Surgery
      - Radiation
      - Systemic Therapy
    - Specific Cancers
      - Breast Cancer
      - Thyroid Cancer
      - Cervical Cancer
      - Hodgkin's Disease and Non-Hodgkin's Lymphoma
      - Ovarian Cancer
      - Acute and Chronic Leukemia
      - Transplacental Malignancy
      - Placental Metastasis
    - Outcome of Children Exposed to Cancer Therapy In Utero
    - Conclusion
    - References
  - Chapter 75. Cancer and Aging
    Arti Hurria, Hyman B. Muss, and Harvey J. Cohen.
    - Life Expectancy and Aging
    - The Biology of Cancer and Aging
    - Physiologic Changes with Aging
    - The Frail Older Patient
    - Evaluation of the Older Patient: Geriatric Assessment
    - Functional Status
    - CoMorbid Medical Conditions
    - Nutrition
    - Cognition
    - Psychological State and Social Support
    - Medication Review: Evaluation for Polypharmacy
    - Comprehensive Geriatric Assessment
    - Knowledge about Older Cancer Patients: UnderRepresentation on Clinical Trials
    - Understanding Barriers to Clinical Trial Enrollment
    - Treatment Tolerance of the Older Patient
      - Surgery
      - Radiation Therapy
      - Chemotherapy
    - Conclusions
    - References
  - Chapter 76. Complementary and Alternative Cancer Therapies
    Barrie R. Cassileth and Andrew Vickers.
    - The Evolution of Complementary and Alternative Medicine
    - Terminology and Definitions
    - Impact on the Healthcare System
    - CAM Use and Users
      - Prevalence and Preferred CAM Therapies
      - CAM Use Among Pediatric Cancer Patients
    - Mainstream Acceptance of CAM
      - Public Access to Information
      - NIH Activity
      - Medical Schools and Medical Centers
      - Recognition by Mainstream Journals and Physicians
      - Mainstream Disapproval
    - CAM Therapies and Practitioners
      - Diet and Nutrition
      - Mind-Body Techniques
      - Bioelectromagnetics
      - Alternative Medical Systems
      - Pharmacologic and Biologic Treatments
      - Manual Healing Methods
      - Herbal Remedies for Cancer
      - Regulatory and Safety Issues: Herbal Remedies and other Food Supplements
    - CAM Practitioners and Practices
      - Training and Licensure of CAM Practitioners
    - CAM Research Issues
    - References
    - Recommended Books
- Section 21: Pain and Palliation
  - Chapter 77. Palliative Care
    Natalie Moryl, Alan C. Carver, and Kathleen M. Foley.
    - The Role of the Oncologist
      - Communication
      - Breaking Bad News
      - Symptom Management
      - Role of Nutrition and Hydration
      - Sedation in the Imminently Dying
      - Facing Death
    - Suffering in the Patient, Family, and Physician
      - Barriers and Challenges for the Physician
    - Guidelines in the Care of the Dying Patient
      - Options for the Care of the Dying Patient
      - Medical Decision Making
    - A Legal Mandate for Palliative Care
    - Conclusion: The Need for Education and Training in End-of-Life Care
    - References
  - Chapter 78. Management of Cancer Pain
    Alan C. Carver and Kathleen M. Foley.
    - Scope of the Problem
    - Barriers to Cancer Pain Management
    - Mechanisms of Cancer Pain
      - Neurophysiology of Pain
    - Types of Pain
      - Somatic Pain
      - Visceral Pain
      - Neuropathic Pain
      - Common Pain Syndromes in Patients with Cancer
    - Strategy for Assessment and Treatment
      - Assessment of Pain
    - Therapeutic Approaches to Cancer Pain
      - Pharmacologic Approaches
    - Psychological and Behavioral Approaches
    - Anesthetic Approaches
      - Trigger-Point Injections
      - Peripheral Nerve Blocks
      - Specific Autonomic Nerve Blocks
      - Nitrous Oxide
      - Ketamine
    - Neurosurgical Approaches
      - Antitumor Approaches
      - Antipain or Analgesic Procedures
    - Sedation in the Imminently Dying
    - Defining the Cancer Pain Research Agenda
    - References
- Section 22: Societal Oncology
  - Chapter 79. Ethics in Oncology
    Ezekiel J. Emanuel and Steven Joffe.
    - Informed Consent
      - Historical Perspective
      - Ethical Standards Regarding Informed Consent
      - Incapacity and Surrogate Consent
      - Is Informed Consent Always the Appropriate Paradigm?
    - Human Subjects Research
      - Historical Perspective
      - Therapy versus Research
      - Ethical Standards for Clinical Research
      - Informed Consent and the Therapeutic Misconception
      - Ethics of Phase I Research
      - Randomized Controlled Trials
      - Placebo Controls
      - Research Involving Stored Tissue
    - Terminating Medical Care
      - Historical Perspective
      - Legal Standards Regarding Terminating Medical Care
      - Advance Care Documents and Durable Powers of Attorney
      - End-of-Life Care Practices
    - Assisted Suicide and Euthanasia
      - Historical Perspective
      - Definitions
      - Ethical Standards Regarding Euthanasia and Assisted Suicide
      - US Supreme Court Ruling on Euthanasia and PAS
      - Euthanasia and PAS in the Netherlands
      - Empirical Data Regarding Euthanasia and PAS
      - Responding to Patient's Request for Euthanasia or Physician-Assisted Suicide
    - Financial Incentives
      - Historical Perspective
      - Ethical Standards for Financial Incentives
      - Empirical Data Regarding Financial Conflicts of Interest
      - Policies Regarding Conflicts of Interest
    - Confidentiality
      - Historical Perspective
      - Ethical Standards Regarding Confidentiality
    - Ethical Issues in Cancer Genetics
      - Genetic Exceptionalism
      - Genetic Tests in High- and Average-Risk Individuals
      - Genetic Testing for Cancer Predisposition in Pediatrics
      - Genetic Information and the Family
      - Protection of Genetic Privacy
      - Research and Genetic Tests
    - References
  - Chapter 80. Cancer and the Law
    Joseph M. Taraska.
    - Elements of Liability
      - The Standard of Care
      - Causation
      - Damages
    - Preventing Legal Complications
      - The Doctor-Patient Relationship
      - Terminating the Doctor-Patient Relationship
    - Consent
    - For Whose Acts Must the Physician Respond?
    - The Physician as an Expert Witness
    - Managed Care
    - Withdrawing Life Support/ Physician-Assisted Suicide and Euthanasia
    - References
  - Chapter 81. The Government and Cancer Medicine
    Anna D. Barker and Hamilton Jordan.
    - Cancer: A Major National Healthcare Priority
    - Legislative History of the National Cancer Program
    - Federal Support for the National Cancer Program
      - Cancer Research Funding and the Federal Budget Process
      - NCI Funding: 1971-2002
      - Funding for Research Project Grants
      - NCI Funding for Specific Cancers
      - Recent Legislative Actions and Funding for NCI
    - Return on Investment from Federal Funds
    - Public Attitudes Concerning Cancer
    - The Cancer Advocacy Movement
      - Breast Cancer Advocacy in the 1990s: Targeted Funding for Specific Cancers
      - The March: Coming Together to Conquer Cancer
      - The National Dialogue on Cancer
      - The National Cancer Legislative Advisory Committee
      - The National Cancer Act of 2002
      - The Impact of the 1990s Cancer Advocacy Movement
    - Federal Policies and Cancer Research
      - Clinical Trials
      - Privacy Regulations
    - The Future
    - References
  - Chapter 82. Clinical Oncology in a Changing Healthcare Environment
    Martin N. Raber and Joseph P. Bailes.
    - Effects of Managed Care on the Providers of Care (Physicians and Hospitals)
    - Effects of Managed Care on Insurers
    - Effects of Managed Care on Employers
    - Effects of Managed Care on Government Programs
    - Effects of Managed Care on Patients and Patient Care
    - Implications for Cancer Care
      - Impact of the Aging on the American Population
      - New Technology
      - Need for Specialized Treatment
      - Multidisciplinary Treatment of Cancer
      - The Need to Incorporate Clinical Research in the Practice of Oncology
    - Demands of Patients Facing Terminal Illnesses
      - Peculiarities of Cancer Care Reimbursement
      - The Changing Face of the Cancer Patient
    - Current Strategies for the Delivery of Cancer Care
      - Guidelines and Pathways
      - Strategies for the Integration of Clinical Research
      - The Economics of Cancer Care
    - Future Directions in Healthcare Reform
    - References
Part VI Cancer Management
- Section 23: Central Nervous System
  - Chapter 83. Primary Neoplasms of the Central Nervous System
    Edward Pan and Michael D. Prados.
    - Epidemiology
    - Risk Factors
    - Molecular Genetics
    - Familial Tumors Syndromes of the Central Nervous system
      - Neurofibromatosis 1
      - Neurofibromatosis 2
      - Von Hippel-Lindau
      - Tuberous Sclerosis
      - Li-Fraumeni Syndrome
    - Histopathology of Neuro-epithelial Central Nervous system Tumors
    - Clinical Presentation
    - Diagnostic Neuroimaging
      - Computed Tomography
      - Magnetic Resonance Imaging
      - Other Imaging Techniques
    - Surgical Diagnosis and Resection
    - Cortical Mapping and Interactive Image-Guided Resections
    - Postoperative Imaging
    - Clinical Trials
    - Glioblastoma Multiforme and Anaplastic Astrocytoma
      - Epidemiology
      - Prognostic Factors
      - Pathology
      - Diagnostic Neuroimaging
      - Surgical Diagnosis and Treatment
      - Radiation Therapy and Chemotherapy
      - Recommendation for Initial Therapy
      - Recurrence
      - Gene Therapy
    - Anaplastic Oligodendroglioma
    - Low-Grade Gliomas
      - Etiology and Epidemiology
      - Prognostic Factors
      - Pathology
      - Clinical Presentation
      - Diagnostic Neuroimaging
      - Treatment Options
      - Treatment of Young Children
      - Recurrence
      - Management Recommendations
    - Ependymoma
      - Epidemiology
      - Pathology
      - Prognostic Factors
      - Clinical Presentation
      - Diagnostic Neuroimaging
      - Treatment
    - Spinal Cord Tumors
      - Etiology and Epidemiology
      - Clinical Presentation
      - Diagnostic Neuroimaging
      - Surgical Treatment
      - Radiation Therapy and Chemotherapy
      - Recurrence
    - Adult Medulloblastomas
      - Epidemiology
      - Pathology
      - Clinical Presentation
      - Diagnostic Neuroimaging
      - Prognostic Factors
      - Treatment
      - Recurrence
      - Conclusion
    - Other Primary Tumors of the Central Nervous System
      - Primary Germ Cell Tumors
      - Meningioma
      - Primary Central Nervous System Lymphoma
      - Neoplastic Meningitis
    - Future Directions
    - Acknowledgments
    - References
  - Chapter 84. Brain Metastases
    Lisa M. DeAngelis and Jerome B. Posner.
    - Pathophysiology of the Metastatic Process
    - Treatment
      - Supportive Care
      - Definitive Treatment
    - References
- Section 24: The Eye
  - Chapter 85. Neoplasms of the Eye
    David H. Abramson, Amy C. Schefler, Ira J. Dunkel, Beryl McCormick, and Kip W. Dolphin.
    - Pediatric Ophthalmic Oncology: Ocular Diseases
      - Benign Disease
      - Primary Malignant Disease (Retinoblastoma)
      - Secondary Malignant Disease (Leukemia)
    - Pediatric Ophthalmic Oncology: Orbital Diseases
      - Benign Disease
      - Malignant Disease
    - Adult Ophthalmic Oncology: Ocular Diseases
      - Benign Disease
      - Malignant Disease (Choroidal Melanoma)
      - Metastatic Disease
      - Cancer-Associated Retinopathies
      - Ocular Lymphoid Tumors
    - Adult Ophthalmic Oncology: Orbital Diseases
      - Introduction to Orbital Tumors
      - Benign and Malignant disease
    - Adult Ophthalmic Oncology: Lid Disease
      - Benign Disease
      - Malignant Disease
    - Ophthalmic Complications of Radiation and Chemotherapy
    - References
- Section 25: Endocrine Glands
  - Chapter 86. Neoplasms of the Endocrine Glands: Pituitary Neoplasms
    Chirag D. Gandhi and Kalmon D. Post.
    - PrL-Secreting Pituitary Adenomas
      - Clinical Presentation
      - Diagnosis
      - Treatment
      - Recommendation
    - GH-Secreting Pituitary Adenomas
      - Clinical Presentation
      - Diagnosis
      - Treatment
    - ACTH-Secreting Adenomas
      - Clinical Presentation
      - Diagnosis
      - Treatment
    - Gonadotropin-Secreting and Nonsecreting Pituitary Adenomas
      - Clinical Presentation
      - Diagnosis
      - Treatment
    - TSH-Secreting Pituitary Adenomas
      - Clinical Presentation
      - Diagnosis
      - Treatment
    - References
  - Chapter 87. Neoplasms of the Thyroid
    Steven I. Sherman and Ann M. Gillenwater.
    - Diagnostic Evaluation of the Solitary Thyroid Nodule
    - Differentiated Thyroid Carcinoma
      - Pathogenesis
      - Pathologic Features
      - Clinicopathologic Staging
      - Primary Surgical Management
      - Postoperative Adjuvant Therapy
      - Management of Differentiated Carcinoma in Special Populations
    - Medullary Thyroid Cancer
      - Initial Surgical Management
      - Adjuvant Radiation Therapy
      - Persistently Elevated Calcitonin
      - Prophylactic Surgery for Gene Carriers
    - Anaplastic Thyroid Carcinoma
      - Treatment and Prognosis
    - References
  - Chapter 88. Neoplasms of the Adrenal Cortex
    David E. Schteingart.
    - Pathogenesis
    - Diagnosis
    - Differential Diagnosis
    - Imaging Characterization
      - Computed Tomography
      - Ultrasonography
      - Magnetic Resonance Imaging
      - ¹³¹I-6β-Iodomethylnorcholesterol Scintigraphy
      - Positron Emission Tomography Scanning
    - Staging
    - Pathologic Diagnosis
    - Carcinoma Management
    - Long-term Treatment Outcome
    - Adrenal Function Inhibitors in Treatment
    - Future Prospects
    - References
  - Chapter 89. Neoplasms of the Diffuse Endocrine System
    Larry K. Kvols.
    - Endocrine Neoplasms of the Gastroenteropancreatic (GEP) System
      - Growth Factors
      - Neuroendocrine Characteristics
      - Anatomic Distribution
      - Carcinoid Tumors
      - Peptide Receptor Radiotherapy
      - Dearterialization
      - External Beam Radiation Therapy
      - Chemotherapy
      - Biologics
      - Adjuvant Therapy
      - Gastrinoma Syndrome
      - Insulinomas
      - Vasoactive Intestinal Peptide Tumor (VIPoma)
      - Glucagonoma Syndrome
      - Somatostatinoma
      - Neurotensinomas
      - Octreotide in Treatment of Malignant Endocrine Tumors of Pancreatic Origin
      - Chemotherapy for Metastatic Islet Cell Carcinomas
    - Parathyroid carcinomas, pheochromocytomas, and multiple endocrine neoplasia syndromes
      - Parathyroid Carcinoma
      - Nonfunctioning Parathyroid Carcinoma
      - Medullary Thyroid Carcinoma
      - Pheochromocytoma
      - Multiple Endocrine Neoplasia Syndromes
    - Men 2A, 2B, and Non-Men Familial Medullary Thyroid Carcinoma
      - Epidemiology
      - Pathologic Characteristics
      - Biologic Characteristics
      - Biochemical and Clinical Features
      - Diagnostic and Screening Tests
      - Surgical Management
      - Treatment of Recurrent or Metastatic Disease
    - References
- Section 26: Head and Neck
  - Chapter 90. Neoplasms of the Head and Neck
    Eduardo M. Diaz, Jr, Erich M. Sturgis, George E. Laramore, Anita L. Sabichi, Scott M. Lippman, and Gary Clayman.
    - Epidemiology
      - Descriptive Epidemiology
      - Risk Factors
      - Carcinogenesis (Field Cancerization)
    - Anatomy
      - Oral Cavity
      - The Pharynx
      - The Larynx
      - Nose and Paranasal Sinuses
      - The Neck
    - Pathologic Assessment
      - Molecular Pathology
    - Diagnosis and Staging
    - Treatment
      - General Principals
      - Natural History and Treatment by Site
      - Radiation Therapy
      - Chemotherapy
    - References
  - Chapter 91. Odontogenic Tumors
    Lewis Clayman.
    - Ectodermal Tumors
      - Ameloblastoma
      - Peripheral Ameloblastoma
      - Solid Ameloblastoma
      - Calcifying Epithelial Odontogenic Tumor (Pindborg Tumor)
      - Calcifying Odontogenic Cyst (Gorlin Cyst, Keratinizing and Calcifying Odontogenic Cyst)
      - Type I
      - Type II: Neoplastic
      - Odontogenic Keratocyst
      - Glandular Odontogenic Cyst
      - Adenomatoid Odontogenic Tumor
      - Squamous Odontogenic Tumor
    - Odontogenic Tumors Derived from Mesoderm
      - Central Odontogenic Fibroma
      - Odontogenic Myxoma
      - Cementoblastoma
      - Central Odontogenic Granular Cell Tumor
      - Clinical
    - Tumors Arising from the Periodontal Membrane
      - Cemento-Ossifying Fibroma (Ossifying Fibroma, Cementifying Fibroma)
      - Nonneoplastic Lesions of Periodontal Ligament Origin
    - Mixed Ectodermal-Mesodermal Odontogenic Tumors
      - Ameloblastic Fibroma
      - Ameloblastic Fibro-odontoma
      - Central Odontogenic Granular Cell Tumor
      - Odontoma
    - Ameloblastic Odontoma (Odontoameloblastoma)
    - Malignant Odontogenic Tumors
      - Treatment
    - References
- Section 27: The Thorax
  - Chapter 92. Cancer of the Lung
    Ara A. Vaporciyan, Merrill S. Kies, Craig W. Stevens, Ritsuko Komaki, and Jack A. Roth.
    - Historical note
    - Factors associated with the development of lung cancer
      - Smoking
      - Age
      - Environmental Causes
      - Familial Predisposition
    - Molecular pathogenesis
      - Oncogenes
      - Growth Factors and Autocrine-Paracrine Growth Control
      - Tumor Suppressor Genes
      - Molecular Abnormalities in Premalignancy
      - Second Primary Cancers
      - Pathology of Lung Cancer
      - Histopathogenesis
      - Histologic Types
      - Solitary Pulmonary Nodule
      - Cancer Screening and Early Detection
    - Natural history
      - Clinical Presentation
      - Manifestations Resulting from Local Tumor Growth and Intrathoracic Spread
      - Manifestations Due to Distant Metastases
      - Systemic, Nonspecific Signs and Symptoms
      - Paraneoplastic Syndromes
      - Diagnostic and Staging Techniques
      - Staging Systems
    - Performance status
      - General Guidelines for Lung Cancer Management
    - Therapy for NSCLC
      - Results by Stage
      - Surgical Treatment
      - Radiotherapy
      - Chemotherapy
    - Therapy for SCLC
      - Surgical Treatment
      - Radiotherapy
      - Chemotherapy
    - Conclusion and Future Prospects
    - References
  - Chapter 93. Malignant Mesothelioma
    A. Philippe Chahinian and Harvey I. Pass.
    - Historical Perspective
    - Incidence and Epidemiology
    - Etiology
      - Epidemiologic and Clinical Evidence of the Role of Asbestos
      - Experimental Evidence for the Role of Asbestos
      - Mechanisms of Oncogenesis by Asbestos
    - Other Etiologic Factors
    - Pathology
    - Clinical Features
      - Pleural Mesothelioma
      - Peritoneal Mesothelioma
      - Paraneoplastic Syndromes
    - Prognostic Factors
    - Other Types of Malignant Mesotheliomas
    - Benign Mesotheliomas
    - Differential Diagnosis
    - Treatment
      - Surgery
      - Induction Therapy
      - Radiotherapy
      - Biologic and Other Therapies
    - Prospectus and Prevention
    - References
  - Chapter 94. Thymomas and Thymic Tumors
    A. Philippe Chahinian.
    - Epidemiology and Etiology
    - Anatomic Pathogenesis
      - Embryology and Anatomy
      - Pathology of Thymomas
    - Clinical Features
    - Associated Paraneoplastic Syndromes
      - Myasthenia Gravis
      - Red Cell Hypoplasia
      - Hypogammaglobulinemia
    - Diagnosis
    - Differential Diagnosis
      - Extrathymic Tumors
      - Other Thymic Tumors
    - Staging
    - Therapy
      - Surgery
      - Radiotherapy
      - Chemotherapy
    - References
  - Chapter 95. Tumors of the Heart and Great Vessels
    A. Philippe Chahinian, David E. Gutstein, and Valentin Fuster.
    - Cardiac Tumors
      - Incidence, Epidemiology, and Etiology
      - Clinical Features
    - Tumors of the Great Vessels
    - References
  - Chapter 96. Primary Germ Cell Tumors of the Thorax
    John D. Hainsworth and F. Anthony Greco.
    - Benign Teratomas of the Mediastinum
    - Malignant Germ Cell Tumors
      - Etiology
      - Epidemiology
      - Histopathology
      - Clinical Characteristics
      - Syndromes Associated with Mediastinal Nonseminomatous Germ Cell Tumors
      - Pretreatment Evaluation and Staging
      - Treatment of Seminoma
      - Treatment of Nonseminomatous Tumors
    - Poorly Differentiated Carcinoma of the Mediastinum
      - Pathologic Evaluation
      - Diagnostic Evaluation and Staging Work-up
      - Treatment
    - References
  - Chapter 97. Metastatic Tumors in the Thorax
    Donald L. Morton and Katharine Yao.
    - Molecular and Genetic Basis for Pulmonary Metastases
    - Diagnosis and Imaging
    - Nonsurgical Treatment of Pulmonary Metastases
      - Chemotherapy
      - Immunotherapy
      - Radiation Therapy
    - Surgical Treatment of Pulmonary Metastases
      - History of Pulmonary Metastasectomy
      - Patient Selection
      - Prognostic Variables
      - Technical Aspects of Pulmonary Metastasectomy
      - Survival Following Surgical Resection by Tumor Histology
    - Pediatric Tumors
    - Summary
    - References
- Section 28: Gastrointestinal Tract
  - Chapter 98. Neoplasms of the Esophagus
    Stephen G. Swisher, Jaffer A. Ajani, Ritsuko K. Komaki, and Mark K. Ferguson.
    - Anatomy and histology
    - Etiology
    - Epidemiology
    - Presentation
    - Treatment overview
    - Diagnosis
    - Pretreatment Assessment
    - Staging evaluation
      - Contrast Radiography of the Esophagus
      - Endoscopy
      - Endoscopic ultrasonography (Endoscopic ultrasonography
      - Computed Tomography of the Chest and Abdomen
      - Bronchoscopy
      - Magnetic Resonance Imaging
      - Positron Emission Tomography
      - Bone scintigraphy
      - Neck Ultrasonography
      - Minimally Invasive Surgical Staging
      - Biologic Staging
      - TNM Staging System
    - Therapy
      - Surgery
      - Radiation Therapy
      - Chemotherapy and Combination Therapy
    - Single-agent chemotherapy
      - Combination Chemotherapy
      - Definitive Chemoradiotherapy
      - Photodynamic Therapy
      - Recommendations for therapy
    - Palliative therapy of esophageal obstruction
    - References
  - Chapter 99. Gastric Cancer
    Paul F. Mansfield, James C. Yao, and Christopher H. Crane.
    - Epidemiology
    - Etiology
    - Proximal Gastric Cancer
    - Histology
      - Lauren Classification System
      - World Health Organization Classification System
    - Clinical Manifestations
    - Pattern of Spread
    - Molecular Biology of Gastric Cancer (Table 99-3)
      - Hereditary Gastric Cancer
      - Epigenetic Changes
      - Tumor-suppressor Genes
      - Cellular Adhesion
      - Tyrosine Kinases
      - Angiogenesis
    - Pathologic and Clinical Staging
    - Therapy of Locoregional Disease
      - Endoscopic Mucosal Resection
      - Surgical Considerations
      - Surgical Controversies
      - Extent of Luminal Resection
      - Node Dissection
      - Multivisceral Resections
      - Technique of Resection
      - Reconstruction
    - Chemoradiotherapy for Gastric Cancer
    - Adjuvant Therapy
      - Chemotherapy
      - Intraperitoneal Therapy
      - Immunotherapy
      - Chemoradiotherapy
      - Intraoperative Radiotherapy
      - Irradiation Technique and Supportive Care
    - Preoperative Chemotherapy
    - Preoperative Chemoradiotherapy
    - Palliative Therapy for Advanced Disease
      - Chemotherapy: Single Agents
      - Combination Chemotherapy
      - Predictors of Response to Therapy
    - Symptom Management
      - Pain
      - Bleeding
    - Obstruction/Dysphagia/ Early Satiety
    - Nutrition
    - Conclusions
    - References
  - Chapter 100. Primary Neoplasms of the Liver
    Paul F. Engstrom, Elin R. Sigurdson, Alison A. Evans, and James F. Pingpank.
    - Epidemiology
      - Frequencies and Types of Cancers
    - Risk Factors
      - Hepatitis B Virus
      - Hepatitis C Virus
      - Cirrhosis and Alcohol
      - Aflatoxins
      - Hemochromatosis and Iron
      - Steroid Hormones
      - Smoking
      - Other Risk Factors
    - Molecular Pathogenesis
    - Prevention
      - Primary Prevention
      - Secondary Prevention
      - Chemoprevention
    - Clinical Presentation
    - Pathologic Diagnosis
    - Staging and Prognosis
      - Serologic Tests of HCC
    - Imaging Modalities
    - Management (Figure 100-3)
      - Localized, Resectable (T1, T2, T3, N0, M0)
      - Localized Unresectable (T2, T3, T4, N0, M0)
      - Metastatic Disease (Any T, N1, or M1)
    - Other Primary Hepatic Neoplasms
    - References
  - Chapter 101. Treatment of Liver Metastases
    Nancy E. Kemeny and Yuman Fong.
    - Imaging Techniques
      - Computed Tomography
      - Magnetic Resonance Imaging
      - Percutaneous and Intraoperative Ultrasonography
      - Positron emission tomography
    - Liver resection
    - Adjuvant chemotherapy
    - Neoadjuvant chemotherapy
    - Systemic chemotherapy
    - Hepatic arterial chemotherapy
      - Toxicity of Hepatic Arterial FUDR Infusion
      - New Approaches to Decrease Hepatic Toxicity
      - Approaches to Increase Response Rate
      - Hepatic Arterial Infusion: Conclusions
    - Cryosurgery
    - Radiofrequency ablation
    - Embolization
    - Chemoembolization
    - Radiation therapy
    - Percutaneous Ethanol Injection
    - Summary
    - References
  - Chapter 102. Gallbladder and Bile Duct Cancer
    Steven A. Curley.
    - Gallbladder Cancer
      - Causative Factors
      - Pathology
      - Clinical Presentation
      - Diagnostic Studies
      - Treatment
      - Multidisciplinary Approaches
    - Bile Duct Cancer
      - Causative Factors
      - Clinical Presentation
      - Pathology
      - Diagnostic Studies
      - Treatment of Intrahepatic Cholangiocarcinoma
      - Hilar Bile Duct Cholangiocarcinoma
      - Prognostic Factors
      - Treatment
    - References
  - Chapter 103a. Neoplasms of the Exocrine Pancreas
    Robert A. Wolff, James Abbruzzese, and Douglas B. Evans.
    - Epidemiology
      - Etiologic Factors
      - Environmental Factors
    - Pathology
      - Histopathology
      - Molecular Pathology
    - Symptom patterns
    - Diagnostic imaging
    - Biliary drainage
    - Treatment of localized, potentially resectable disease
      - Surgery
      - Pathologic (surgical) staging
      - Prognostic Factors
      - Postoperative (adjuvant) therapy
      - Preoperative (neoadjuvant) therapy
      - Approach to the patient with potentially resectable disease
    - Treatment of locally advanced disease
      - Chemoradiation therapy
      - Downstaging locally advanced, unresectable disease
      - Intraoperative radiation therapy
      - Management of gastric outlet obstruction
      - Tumors of the pancreatic body and tail
      - Approach to the patient with locally advanced disease
    - Treatment of metastatic disease
      - Single-agent chemotherapy
      - Camptothecins
      - Other agents tested in advanced pancreatic cancer
      - Combination chemotherapy
      - Regional chemotherapy
      - Hormonal Therapy
      - Future approaches to the treatment of systemic disease
      - Approach to the patient with metastatic disease
    - References
  - Chapter 103b. Neoplasms of the Ampulla of Vater
    Tina W.F. Yen, Robert A. Wolff, and Douglas B. Evans.
    - Diagnostic Evaluation
    - Treatment
      - Potentially Resectable Disease
      - Adjuvant Therapy and the Management of Locally Advanced Disease
      - Metastatic Disease
    - Associated Syndromes
    - Conclusions
    - References
  - Chapter 104. Neoplasms of the Small Intestine
    Elizabeth G. Grubbs and Douglas S. Tyler.
    - Clinical Presentation
    - Diagnostic Imaging
    - Treatment
      - Benign Tumors
      - Malignant Neoplasms
      - Metastatic Neoplasms
    - References
  - Chapter 105. Neoplasms of the Vermiform Appendix and Peritoneum
    Elizabeth G. Grubbs and Douglas S. Tyler.
    - Tumors of the Appendix
      - Malignant Tumors
    - Neoplasms of the Peritoneum
      - Mesotheliomas
      - Primary Peritoneal Carcinoma
      - Pseudomyxoma Peritonei
      - Angiosarcoma
      - Malignant Ascites
    - References
  - Chapter 106. Adenocarcinoma of the Colon and Rectum
    Miguel A. Rodriguez-Bigas, Edward H. Lin, and Christopher H. Crane.
    - Pathology
    - Staging
    - Epidemiology of Colorectal Cancer
      - Cancer Statistics
      - Location of Tumors
    - Epidemiologic Risk Factors
      - Dietary Risk Factors
      - Alcohol and Tobacco
      - Hormone Replacement Therapy and Reproduction
      - Physical Activity and Total Body Mass
      - Polymorphisms
      - Occupational exposures
      - Nonsteroidal Antiinflammatory Drugs
    - Genetic Pathways in Colorectal Cancer
      - Genes Involved in CIN
      - Mutator Pathway
      - Other Pathways
    - Tumor Markers
      - Carcinoembryonic Antigen
    - Molecular Markers for Prognosis
      - DNA Ploidy
      - Ki-ras
      - TP53
      - 18q Deletion
      - Microsatellite Instability
      - Thymidylate Synthase, Thymidine Phosphorylase, and Dihydropyrimidine Dehydrogenase
    - Colorectal Cancer Screening and Risk Factors for Colorectal Cancer
      - Risk factors for Colorectal Cancer
    - Surgical Anatomy
    - Colorectal Cancer Management
      - Clinical presentation
    - Surgical Management of Colorectal Cancer
      - Colon Cancer
      - Rectal Cancer
      - Surgical Considerations in Adjuvant Therapy
      - Radiation Therapy
      - Risk of Recurrence with Surgical Resection Alone
      - Adjuvant Chemoradiotherapy for Rectal Cancer
      - Postoperative Chemoradiation
      - The Role of Radiotherapy in Colon Cancer
    - Adjuvant Treatment of Colon Cancer
      - Stage III Colon Cancer
      - Stage II Colon Cancer
      - New Generation Adjuvant Trials
    - Immunotherapy
      - BCG Vaccination
      - Monoclonal Antibody 17-1A
      - Levamisole
      - Interleukin-2
      - CEA Vaccines
    - Stage IV Colorectal Cancer
      - Fluoropyrimidines
      - Oral Fluoropyrimidines
      - Thymidylate Synthase Inhibitors
      - Novel Combination Cytotoxic Regimens
      - Novel Therapeutic Modalities
    - Future Directions
    - References
  - Chapter 107. Neoplasms of the Anus
    Brenda Shank, Warren E. Enker, and Marshall S. Flam.
    - Gross and Microscopic Anatomy
    - Epidemiology
    - Etiology
    - Pathology
    - Diagnosis
    - Staging
    - Treatment
      - Locoregional Disease
      - Inguinal Lymph Node Involvement
      - Metastatic Disease
    - Melanoma
    - References
- Section 29: Genitourinary Tract
  - Chapter 108. Renal Cell Carcinoma
    Jerome P. Richie and Philip W. Kantoff.
    - Pathogenesis
    - Incidence
    - Etiology
    - Molecular Biology
    - Clinical Features
    - Radiographic Evaluation
      - Intravenous Urography
      - Ultrasonography
      - Cyst Puncture
      - Computed Tomography
      - Magnetic Resonance Imaging
    - Staging and Grading
      - Clinical Staging
      - Pathologic Grading
      - Pathologic Staging
    - Surgical Treatments
      - Regional Lymphadenectomy
      - Renal Vein and Inferior Vena Caval Involvement
      - Prognosis
      - Tumors in the Solitary Kidney or Bilateral Simultaneous Tumors
      - Preoperative Arterial Embolization
    - Adjuvant Therapy
    - Treatment of Metastatic Disease
      - Hormonal Treatment
      - Chemotherapy
      - Interferon
      - Interleukin 2 and Other Forms of Immunotherapy
      - Therapy Directed at Vascular Endothelial Growth Factor
    - Surgical Considerations for Metastatic Disease
      - Solitary Metastasis
      - Multiple Metastases
    - Sarcomas of Renal Origin
    - Wilms Tumor (Nephroblastoma)
    - Renal Oncocytoma
    - References
  - Chapter 109. Neoplasms of the Renal Pelvis and Ureter
    Jerome P. Richie and Philip W. Kantoff.
    - Etiologic Factors
    - Histopathology
    - Diagnosis
      - Clinical Presentation
      - Cytology
      - Intravenous Pyelography
      - Ureteroscopy
      - Brush Biopsy
    - Staging
    - Treatment
      - Operative Therapy
      - Endoscopic Therapy
    - Prognosis
      - Adjuvant Therapy
      - Chemotherapy
    - Secondary Tumors of the Ureter
      - Drop Metastases
      - Metastatic Ureteral Tumors
      - Tumor from Direct Extension
    - References
  - Chapter 110. Bladder Cancer
    Timothy D. Gilligan, Graeme S. Steele, Anthony L. Zietman, and Philip W. Kantoff.
    - Epidemiology
    - Biology
    - Pathology
    - Signs and Symptoms
    - Diagnostic Evaluation
      - Cystoscopy
      - Urinary Cytology
      - Imaging
      - Bladder Biopsy and Transurethral Resection of Bladder Tumors
      - Bimanual Examination
    - Staging
    - Superficial Bladder Carcinoma
      - Natural History
      - Carcinoma in Situ
      - Intravesical Therapy
    - Muscle-Invasive Bladder Cancer
      - Radical Cystectomy
      - Urinary Diversions
      - Preoperative Radiation Therapy
      - Postoperative Radiation Therapy
      - Bladder Preservation
      - Neoadjuvant and Adjuvant Chemotherapy
    - Chemotherapy for Metastatic Disease
      - Combination Regimens
      - Single Agents
      - Second-Line Chemotherapy
    - Adenocarcinoma of the Bladder
    - Squamous Cell Carcinoma
    - References
  - Chapter 111. Neoplasms of the Prostate
    William K. Oh, Mark Hurwitz, Anthony V. D'Amico, Jerome P. Richie, and Philip W. Kantoff.
    - Epidemiology and Risk Factors
    - Biology of Prostate Cancer
      - Normal Histology and Anatomy
      - Premalignant Lesions
      - Histology of Prostate Cancer
      - Molecular Pathogenesis
    - Screening for Prostate Cancer
      - Screening in the PrePSA Era
      - Prostate-specific Antigen
      - Improving the Utility of PSA Testing
      - Latent Prostate Cancer
      - Current Recommendations for Screening
    - Diagnosis and Staging of Prostate Cancer
      - Newer Staging Tests
    - Prognostic Factors in Localized Prostate Cancer
    - Management of Localized Prostate Cancer
      - Expectant Management
      - Radical Prostatectomy
    - Radiation Therapy
      - Treatment Technique
      - Radiation Therapy and Outcomes
      - Intermediate-risk Prostate Cancer
      - High-risk Prostate Cancer
      - Postprostatectomy Radiation Therapy
      - Palliative Radiation Therapy and Radiopharmaceuticals
      - Complications of Radiation Therapy
    - Comparison of Treatment Options for Localized Prostate Cancer
    - Management of Locally Advanced Prostate Cancer
      - T3 Disease
      - Node-positive Prostate Cancer
    - Management of Disseminated Cancer
      - Testicular Androgen Suppression
      - Combined Androgen Blockade
      - Early Versus Delayed Hormonal Therapy
      - Investigational Approaches to Hormonal Therapy
    - Hormone-refractory Prostate Cancer
      - Secondary Hormonal Maneuvers
      - Cytotoxic Chemotherapy
      - Bone-directed Therapies
      - Prognosis
    - New Approaches to Prostate Cancer Therapy
      - Differentiation Therapy
      - Induction of Apoptosis
      - Signal Transduction Inhibitors
      - Vaccine therapy
      - Angiogenesis Inhibitors
      - Chemoprevention
    - References
  - Chapter 112. Tumors of the Penis and Urethra
    Donald F. Lynch, Jr.
    - Cancer of the Penis
      - Histopathology
      - Epidemiology and Etiology
      - Carcinoma in Situ
      - Invasive Squamous Carcinoma
      - Verrucous Carcinoma
      - Other Malignancies
      - Natural History and Course
      - Tumor Staging
      - Surgical Treatment
      - Management of the Regional Lymph Nodes
      - Tumor Grade
      - Pelvic Lymphadenectomy
      - Radiotherapy
      - Chemotherapy
      - Prognosis
      - Conclusions
    - Carcinoma of the Urethra
      - Female Urethral Carcinoma
      - Staging
      - Surgical Management
      - Radiation Therapy
      - Chemotherapy and Combined Therapy
      - Prognosis
      - Male Urethral Carcinoma
      - Summary
    - References
  - Chapter 113. Testis Cancer
    Nasser Hanna, Robert Timmerman, Richard S. Foster, Bruce J. Roth, Lawrence H. Einhorn, and Craig R. Nichols.
    - Epidemiology
      - Incidence
      - Risk Factors
    - Pathology
      - Seminoma
      - Embryonal Carcinoma
      - Yolk Sac Carcinoma
      - Choriocarcinoma
      - Teratocarcinoma
      - Teratoma
      - Gonadal Stromal Tumors
    - Clinical Presentation
      - Diagnosis
      - Tumor Markers
    - Staging
    - Therapy
      - Carcinoma in Situ
      - Nonseminoma: Early Stage
      - Seminoma Early Stage
    - Therapy for Disseminated Disease
      - Chemotherapy: Precisplatin
      - VAB Regimens: Memorial Sloan-Kettering Cancer Center
      - Indiana University Studies
    - Treatment of Good-Risk Disseminated Germ Cell Tumors
    - Treatment of Patients with “Poor-Risk” Disseminated Disease
      - High-Dose Chemotherapy as Primary Treatment of Poor-Risk Disease
      - Postchemotherapy Surgery
      - Chemotherapy of Seminoma
      - Salvage Chemotherapy
      - Standard Salvage Therapy
    - High-Dose Chemotherapy as Initial Salvage Therapy
    - Treatment of Multiply Recurrent Germ Cell Cancer
      - High-Dose Chemotherapy for Multiply Recurrent Germ Cell Cancer
      - Other Investigations
      - Salvage Surgery
      - New Agents
    - Special Situations
      - Late Relapse
    - Long-Term Toxicity of Chemotherapy
      - Nephrotoxicity
      - Vascular Toxicity
      - Neurotoxicity
      - Second Malignancies
      - Fertility
      - Pulmonary Toxicity
    - Long-Term Toxicity of Radiation Therapy
      - Cardiopulmonary Toxicity
      - Gastrointestinal Toxicity
      - Fertility
      - Second Malignancies
      - Sanctuary Sites and CNS Metastases
    - Extragonadal Germ Cell Tumors
    - Unrecognized Germ Cell Tumor Syndrome
    - Acknowledgment
    - References
- Section 30: Female Reproductive Organs
  - Chapter 114. Neoplasms of the Vulva and Vagina
    Jacob Rotmensch and S. Diane Yamada.
    - Cancer of the Vulva
      - Vulvar Atypias
      - Paget Disease
      - Invasive Vulvar Carcinomas
    - Cancer of the Vagina
      - Premalignant Vaginal Disease
      - Invasive Carcinomas of the Vagina
      - Clear Cell Adenocarcinoma of the Vagina
      - Vaginal Melanomas
      - Rare Vaginal Tumors in Young Females
    - References
  - Chapter 115. Neoplasms of the Cervix
    Anuja Jhingran, Patricia J. Eifel, J. Taylor Wharton, and Guillermo Tortolero-Luna.
    - Epidemiology
      - Incidence and Mortality
      - Risk Factors for Cervical Neoplasia
      - Summary
    - Histologic classification of epithelial tumors
      - Squamous Cell Carcinoma
      - Adenocarcinoma
      - Other epithelial tumors
    - Natural history of carcinomas of the uterine cervix
    - Diagnosis and treatment of precancerous lesions
      - Management of Low-Grade Cytologic Abnormalities
      - Management of High-Grade Cytologic Abnormalities
      - New Concepts in Diagnosis and Prevention
    - Diagnosis and treatment of invasive lesions
      - Patterns of Spread
      - Clinical Symptoms
      - Diagnosis
      - Evaluation and Staging
      - Prognostic Factors
      - Surgical Treatment Options
      - Outcomes After Surgical Treatment
    - Radiation therapy
      - Treatment Options
      - Treatment Duration
      - Patient Selection
      - Outcomes
      - Complications
    - Current practice by disease stage
      - Carcinoma in situ and stage IA1 disease
      - Stage IA2 Disease
      - Stage IB1 and Small Stage IIA Disease
      - Stage IB2 Disease
      - Stage IIB–IVA disease
      - Metastatic Disease
      - Unsuspected invasive cancer discovered after simple hysterectomy
      - Recurrent disease
    - Future opportunities
    - References
  - Chapter 116. Endometrial Cancer
    Jamal Rahaman and Carmel J. Cohen.
    - Risk Factors
    - Pathology
      - Endometrial Hyperplasia
      - Endometrial Adenocarcinoma
      - Adenosquamous Carcinoma
      - Uterine Papillary Serous Carcinoma
      - Endometrial Papillary Adenocarcinoma
      - Clear Cell Carcinoma
    - Diagnosis
    - Staging
    - Prognostic Factors
      - Histologic Type
      - Tumor Grade
      - Myometrial Invasion
      - Capillary-Lymphatic Space Invasion
      - Positive Peritoneal Cytology
      - Race
      - Hormone Receptor Status
      - Tumor Ploidy and Kinetics
    - Oncogene Activation and Loss of Tumor-Suppressor Function
    - Treatment of Primary Disease
      - Surgery
      - Radiation Therapy
    - Treatment of Recurrent Disease
      - Cytotoxic Chemotherapy
      - Hormone Therapy
    - Future
    - References
  - Chapter 117. Neoplasms of the Fallopian Tube
    Carmel J. Cohen and Jamal Rahaman.
    - Epidemiology
    - Clinical Presentation
    - Preoperative Diagnosis
    - Clinicopathologic Classification and Staging
    - Patterns of Spread
    - Prognostic Factors
    - Treatment
      - Surgical Therapy
      - Radiation Therapy
      - Chemotherapy
    - Prognosis
    - Other Malignant Fallopian Tube Neoplasms
    - References
  - Chapter 118. Ovarian Cancer
    Jonathan S. Berek and Robert C. Bast, Jr.
    - Epithelial Ovarian Cancer
      - Etiology and Epidemiology
      - Prevention
      - Genetic Risk for Epithelial Ovarian Cancer
      - Embryology
      - Biology and Prognosis of Ovarian Neoplasms
      - Classification and Pathology
      - Patterns of Spread
      - Clinical Features
      - Diagnosis
      - Screening
      - Staging of Ovarian Cancer
      - Treatment of Early Stage Ovarian Cancer
      - Treatment of Advanced Stage Epithelial Ovarian Cancer
      - Assessment of Response in Patients Who are Clinically Free of Disease
      - Survival of Patients with Advanced Ovarian Cancer
    - Nonepithelial Ovarian Cancer
      - Germ Cell Malignancies
      - Diagnosis
      - Dysgerminomas
      - Immature Teratomas
      - Endodermal Sinus Tumors
      - Embryonal Carcinoma
      - Choriocarcinoma of the Ovary
      - Mixed Germ-Cell Tumors
      - Sex Cord-Stromal Tumors
      - Granulosa-Stromal Cell Tumors
      - Uncommon Ovarian Tumors
      - Small-Cell Carcinomas
    - References
  - Chapter 119. Gestational Trophoblastic Disease
    Ross S. Berkowitz and Donald P. Goldstein.
    - Historical Perspective
    - Epidemiology
      - Etiology
    - Histopathologic Classification of GTD
    - Molecular Pathogenesis
    - Natural History
      - Presentation of Complete Molar Pregnancy
      - Presentation of Partial Molar Pregnancy
      - Postmolar GTT
      - Presentation of Nonmetastatic GTT
      - Presentation of Metastatic GTT
    - Diagnosis
      - Complete and Partial Molar Pregnancy
      - Persistent GTT
    - Staging
    - Therapy
      - Molar Pregnancy
      - GTT
      - Stage I Therapy
    - Results of Therapy
      - Stage I GTT
      - Stages II and III GTT
      - Stage IV GTT
    - Subsequent Pregnancies
    - Second Cancers
    - References
  - Chapter 120. Gynecologic Sarcomas
    Jamal Rahaman and Carmel J. Cohen.
    - Clinical Profile
      - Uterine Endometrial Stromal Tumors
      - Mixed Tumors
      - Uterine Myometrial Tumors
    - Diagnosis
    - Sarcoma-Like Variants
    - Patterns of Spread
    - Prognostic Factors and Prognosis
    - Nonuterine Gynecologic Sarcomas (Figure 120-1)
      - Vulva
      - Vagina
      - Ovary
      - Fallopian Tube
    - Surgical Treatment
    - Postsurgical Therapy for Gynecologic Sarcomas
    - Hormone Therapy
    - Radiation Therapy for Leiomyosarcoma
    - Radiation Therapy for Malignant Mixed Müllerian Tumors
    - Chemotherapy
      - Single-Agent Therapy
    - Combination Therapy
      - Randomized Trials
      - Phase II Trials
      - Adjuvant Therapy for Limited Disease
    - References
- Section 31: The Breast
  - Chapter 121. Neoplasms of the Breast
    Richard G. Margolese,, Gabriel N. Hortobagyi,, and Thomas A. Buchholz,.
    - Pathology
      - Histologic Types
      - Tumor Characteristics
      - Lymph Node Characteristics
      - Nonepithelial Neoplasms of the Breast
      - Relation of Tumor Characteristics to Outcome
    - Epidemiology
    - Risk Factors
      - Gender
      - Age
      - Socioeconomic Class
      - Ethnicity
      - Family History/Genetics
      - Endocrine and Reproductive Risk Factors
      - Exogenous Hormones
      - Abortion
      - Physical Activity
      - Environmental Factors, Obesity, and Diet
      - Alcohol Consumption
      - Radiation Exposure
      - Environmental Factors
      - Benign Breast Disease
      - Mammographic Parenchymal Pattern
      - Other Risk Factors
      - Combinations of Factors
    - Breast Cancer Biology
      - Regulation of Breast Cancer Growth
      - Estrogen and Progesterone Receptors
    - Natural History and Prognostic Markers
      - Age and Menopausal Status
      - Axillary Lymph Node Involvement
      - Tumor Size
      - Histologic Variables
      - Histologic Grade or Differentiation
      - Angiogenesis Markers
      - Markers of Proliferative Capacity
      - Steroid Hormone Receptors
      - Molecular Genetic Alterations
      - Bone Marrow Involvement
      - Investigational Markers
      - Prognostic Indices
      - Clinical Use of Prognostic Factors
    - Diagnosis and Screening
      - Patient History
      - Physical Examination
      - Screening
      - Role of Breast Self-Examination
      - Differential Diagnosis
      - Diagnostic Aids: Imaging
      - Diagnostic Aids: Fine-Needle and Core Biopsy
    - Staging and Classification
      - Biologic Markers: Detection and Staging
    - Psychosocial Aspects of Breast Cancer
    - Surgical Biology
      - Breast Cancer as a Systemic Disease
      - Biologic Redefinition of the Role of Lymphatics and Lymph Nodes
      - A Biologic Basis for Breast Cancer Surgery
      - Breast-Removal Treatment Regimens
      - Lumpectomy Technique
      - Lumpectomy for Subareolar Tumors or for Tumors Greater than 4 cm
      - Axillary Dissection
      - Breast Biopsy: The Two-Stage Procedure and Fine-Needle Aspiration
      - Paget Disease
      - Inflammatory Carcinoma
      - Management of the Uninvolved Breast
      - Lobular Carcinoma In Situ
      - Reconstruction
      - Silicone Implants
    - The Role of Radiation for invasive Breast Cancer
      - Radiation Reduces Ipsilateral Breast Tumor Recurrences
      - Contraindications for Breast Conservation Therapy
      - Factors Affecting Outcome of Breast Conservation Therapy
      - New Radiation Treatment Approaches for Early-Stage Breast Cancer
      - Treatment Sequencing for Early-Stage Breast Cancer
      - Postmastectomy Radiation
      - Morbidity of Radiation Therapy
      - Palliative Radiotherapy
    - Systemic Therapy of Breast Cancer
      - Specific Endocrine Therapies
      - Interference with Hormonal Action
      - Cytotoxic Chemotherapy
      - Targeted Therapies
    - Systemic Adjuvant Therapy
      - Early Trials
      - Adjuvant Therapy for Node-negative Patients
      - Endocrine Therapy
      - Chemotherapy
      - Adjuvant Therapy for Node-Positive Patients
    - Endocrine Therapy
      - Tamoxifen
      - Adjuvant Ovarian Ablation
      - Aromatase Inhibitors (AIs)
      - Preoperative (Neoadjuvant) Chemotherapy for Operable Breast Cancer
      - Local Recurrence in Preoperative Chemotherapy
    - Management of Metastatic Breast Cancer
      - General Considerations
      - Diagnostic Evaluation
      - General Therapeutic Guidelines
      - Endocrine Therapies for Metastatic Breast Cancer
      - Cytotoxic Chemotherapy for Metastatic Breast Cancer
      - Dose-Intensive Chemotherapy
      - Combined Hormonal Therapy and Chemotherapy
      - Targeted Therapies for Metastatic Breast Cancer
    - Special Issues Regarding Therapy
      - Pregnancy and Breast Cancer
      - Male Breast Cancer
      - Inflammatory Breast Cancer (InflBC)
      - Treatment of the Elderly
    - Prevention of Invasive Breast Cancer in Women with Intraductal Carcinoma In Situ (DCIS)
      - B-17, The First Randomized Clinical Trials for DCIS
      - B-24, The Second Randomized Clinical Trial for DCIS
      - Relation of the B-17 and B-24 Trials to Each Other and to the NSABP Prevention Trial (P-1)
      - Conclusion
    - Prevention of Invasive Breast Cancer in Women at Increased Risk
      - P-1 Study Design, Participant Eligibility, Risk Assessment, and Analysis
      - Participant Characteristics
      - The Benefit from Tamoxifen
      - Adverse Effects from Tamoxifen
      - Relationship Between the Beneficial and Harmful Effects of Tamoxifen
      - Candidates for Tamoxifen
      - The Meaning of Prevention
      - Future Steps: The MORE Trial, Raloxifene, and the STAR Trial
    - Perspectives
    - References
      - Pathology, Epidemiology, Risk Factors, Breast Cancer Biology, Natural History and Prognostic Markers
      - Diagnosis and screening, Staging and classification, Psychological aspects of breast cancer, Surgical biology
      - The Role of Radiation for Invasive Breast Cancer
      - Systemic Therapy of Breast Cancer, systemic adjuvant therapy, endocrine therapy
      - Management of Metastatic Breast Cancer, special issues regarding therapy, prevention of invasive breast cancer in women with intraductal carcinoma in situ (DCIS), prevention of invasive breast cancer in women at increased risk, perspectives
    - Additional Readings
- Section 32: The Skin
  - Chapter 122. Malignant Melanoma
    Donald L. Morton, Richard Essner, John M. Kirkwood, and Robert C. Wollman.
    - History of Melanoma
    - Epidemiology and Etiology
    - Familial Melanoma
    - Precursor Lesions
      - Dysplastic Nevus Syndrome (Familial Atypical Mole/Melanoma Syndrome)
      - Congenital Nevi
      - Melanocytes as Antecedent Lesions
      - Biologic Growth Phases
    - Clinical Characteristics
      - Classification
      - Staging
    - Prognostic Features of Clinically Localized Disease
      - Ulceration
      - Other Histologic Prognosticators
      - Gender
      - Anatomic Site
      - Pregnancy
    - Prognostic Features of Regional Lymph Node Metastases
      - Lymph Node Metastases from Unknown Primary Site
    - Prognostic Features of Distant Metastases
      - Disease-Free Interval
    - Management of Primary Melanoma
      - Surgical Resection and Biopsy
      - Radiation Therapy
      - Adjuvant Treatment by Limb Perfusion
    - Management of Regional Lymph Nodes
      - Elective Versus Therapeutic Lymphadenectomy
      - Microstage of Primary Melanoma and Risk of Nodal Metastases
      - Adjuvant Therapy
      - Management of Locally Recurrent and In-Transit Melanomas
    - Management of Distant Metastases
      - Surgery
      - Immunotherapy
      - Chemotherapy
      - Hormonal Therapy
      - Radiation Therapy
    - Future Horizons
    - References
  - Chapter 123. Other Skin Cancers
    Victor A. Neel and Arthur J. Sober.
    - Ultraviolet Radiation in the Genesis of Skin Cancers
    - Tumors Arising from the Epidermis
      - Actinic Keratosis
      - Arsenical Keratosis
      - Human Papillomavirus Induced Premalignant Papules
      - Epidermodysplasia Verruciformis
      - Bowenoid Papulosis
      - Keratoacanthoma
      - Squamous Cell Carcinoma
      - Basal Cell Carcinoma
      - Basal Cell Nevus Syndrome (Gorlin Syndrome)
      - Merkel Cell Carcinoma
    - Tumors Arising from Mucosa
      - Leukoplakia
    - Tumors Arising from Dermis
      - Dermatofibrosarcoma Protuberans
      - Malignant Fibrous Histiocytoma
      - Cutaneous Angiosarcoma
    - Tumors Arising from Appendages
      - Nevus Sebaceous
      - Sebaceous Carcinoma
      - Extramammary Paget Disease
    - Benign Cutaneous Tumors Associated with Cancer Syndromes
      - Trichilemmoma (In Cowden Disease)
      - Sebaceous Adenoma (In Muir-Torre Syndrome)
      - Multiple Mucosal Neuromas (Multiple endocrine neoplasia 2B, MEN2B)
    - Metastatic Tumors to the Skin
    - References
- Section 33: Bone And Soft Tissue
  - Chapter 124. Bone Tumors
    Dempsey Springfield and Gerald Rosen.
    - Staging
      - Benign
      - Malignant
    - Biopsy
    - Surgery
      - Types of Reconstruction
      - Reconstruction as a Function of Location
      - Special Considerations for the Skeletally Immature
      - Limb Salvage versus Amputation Surgery
      - Surgery for Metastatic Disease
    - Chemotherapy
    - Radiation therapy
      - Treatment Planning and Techniques
      - Acute Side Effects
      - Late Effects
    - Specific bone tumors
      - Benign Bone Tumors
      - Malignant Bone Tumors
      - Osteosarcoma
    - References
  - Chapter 125. Soft-Tissue Sarcomas
    Peter W.T. Pisters and Brian O'Sullivan.
    - Etiology
    - Screening
    - Clinical Presentation, Classification, and Diagnosis
      - Sites of Origin
      - Clinical Presentation
      - Histopathologic Classification
      - Imaging
    - Staging and Prognostic Factors
      - Staging
      - Conventional Prognostic Factors
      - Potential Molecular Prognostic Factors
    - Treatment of Localized Primary Disease of the Extremities
      - Surgery
      - Radiotherapy
      - Chemotherapy
      - Combined Preoperative Chemotherapy and RT
    - Treatment of Locally Advanced Disease
      - Hyperthermic Isolated Limb Perfusion
      - Radiation Alone
    - Treatment of Metastatic Disease
      - Clinical Problem of Metastases
      - Resection of Metastatic Disease
      - Chemotherapy for Metastatic Disease
    - Management of Local Recurrence
    - Signal Transduction Inhibition for Gastrointestinal Stromal Tumors and Dermatofibrosarcoma Protuberans
      - Gastrointestinal Stromal Tumors
      - Dermatofibrosarcoma Protuberans
    - Retroperitoneal Sarcomas
      - Pre- and Postoperative Radiotherapy Approaches
      - Chemoradiation Approaches
    - Additional Issues in Soft-Tissue Sarcoma Management
      - Functional Outcome and Morbidity of Treatment
      - Molecularly and Pathobiologically Based Sarcoma Management
    - Summary
    - References
- Section 34: Hematopoietic System
  - Chapter 126. The Myelodysplastic Syndrome
    Lewis R. Silverman.
    - History
    - Classification
    - Etiology
    - Pathobiology
      - Clonal Origin
      - In Vitro Progenitor Growth Characteristics
      - Bone Marrow Microenvironment
      - Signal Transduction
      - Cytogenetics
      - Oncogenes
      - Clinical and Laboratory Features
      - Pathogenesis and Relation to Leukemic Transformation
      - Treatment
    - Clinical Management
    - Future Directions
    - References
  - Chapter 127. Acute Myeloid Leukemia in Adults
    Charles A. Schiffer and Richard M. Stone.
    - Pathogenesis and Etiology
    - Morphologic Classification and Clinical and Laboratory Correlates
      - Peripheral Blood
      - MO (Minimally Differentiated AML)
      - FAB M1 (Myeloid Leukemia without Maturation)
      - FAB M2 (Myeloid Leukemia with Maturation)
      - FAB M3 (Acute Progranulocytic Leukemia)
      - FAB M4 (Myelomonocytic Leukemia)
      - FAB M4EO (Myelomonocytic Leukemia with Eosinophilia)
      - FAB M5 (Monocytic Leukemia)
      - FAB M6 (Erythroleukemia)
      - FAB M7 (Megakaryocytic Leukemia)
      - Hybrid Leukemias
    - Presenting Signs and Symptoms
    - Therapy
      - Induction Therapy General Principles
      - Postremission Therapy
      - Therapy of Relapsed and Refractory AML
    - Other Supportive Care and Therapeutic Approaches
      - Hematopoietic Growth Factors
      - Minimal Residual Disease
      - Prognostic Factors
    - Complications
      - Hyperleukocytosis
      - Central Nervous System Leukemia
      - Ophthalmic Complications
      - Pregnancy
      - Metabolic Abnormalities
    - Summary
    - References
  - Chapter 128. Chronic Myeloid Leukemia
    Richard T. Silver.
    - Incidence and Epidemiology
    - Etiology
    - Clinical and Hematologic Characteristics
    - Terminal Chronic Myeloid Leukemia
    - Pathophysiology
    - Cytogenetics
    - Fluorescence in Situ Hybridization Test
    - Molecular Biology of CML
    - Treatment
      - Treatment with Interferon and Other Drugs
      - Summary of Interferon-Based Treatment Compared to Hydroxyurea and Busulfan
      - Relevance of Risk Profile
      - Hydroxyurea and Busulfan
      - Busulfan (Myleran)
    - Treatment of Blast Crisis Other than with Imatinib Mesylate
    - Bone Marrow Transplantation
    - Imatinib Mesylate
    - Management of CML in 2003
    - References
  - Chapter 129. Adult Acute Lymphocytic Leukemia
    Guillermo Garcia-Manero, Hagop M. Kantarjian, and Charles A. Schiffer.
    - Classification
    - Genetic and Molecular Alterations
    - Cytogenetic-Molecular Differences in Childhood and Adult ALL
    - Evaluation of Minimal Residual Disease
    - Pharmacogenomics and Mechanism of Drug Resistance
    - Epidemiology and Etiology
    - Clinical Presentation and Laboratory Characteristics
    - Treatment
      - Induction Therapy
      - Value of Consolidation Therapy
      - Role of Maintenance Therapy
      - Disease-specific Treatment Modifications
      - Allogeneic Stem Cell Transplantation (SCT)
      - Autologous Bone Marrow Transplantation
    - Central Nervous System Prophylaxis and Therapy
    - Prognosis Factors in Adult ALL
    - Salvage Therapy for refractory or Relapsed ALL
    - Summary and Future Directions in Adult ALL
    - References
  - Chapter 130. Chronic Lymphocytic Leukemia
    Kanti R. Rai and Michael J. Keating.
    - Historical Perspective
      - Incidence and Epidemiology
    - Pathogenesis and Etiology
      - Familial CLL
      - CLL in Monozygotic Twins
    - Immunobiology and Immunophenotype of CLL cells
    - Clinical Consequences of Defective B- and T-Cell Functions
      - Cytogenetics
      - Molecular Genetics
      - p53
      - IgV Gene Mutation
      - Clinical Aspects
      - Diagnosis
      - Differential Diagnosis
      - T-Cell Chronic Lymphocytic Leukemia
      - Clinical Presentation
    - Natural History and Terminal Events
    - Clinical Staging and Other Prognostic Features
      - Staging System of Rai and Colleagues
      - Method of Binet and Colleagues
      - Other Staging Systems
      - Criteria Predictive of Course of Disease in the Low- and Intermediate-Risk Groups
    - Treatment
      - Indications for Treatment
      - Goals of Therapy
      - Chemotherapy
      - Corticosteroids
      - Combination Regimens
      - Comparative Trials in CLL (French Co-operative Studies)
      - Purine Analogs
      - Comparative Studies
      - New Regimens
      - Radiation Therapy
      - Leukapheresis Therapy
      - Splenectomy
      - Stem Cell Transplantation
      - Minimal Residual Disease
      - Immunotherapy
      - Chemoimmunotherapy
      - Clinical Management of Patients with CLL
      - Infections in CLL
      - Management of Anemia
      - Thrombocytopenia
      - CLL Variants
      - Recommended Approach to Therapy of Patients with CLL
    - Conclusion
    - References
  - Chapter 131. Hairy Cell Leukemia
    Harvey M. Golomb and James W. Vardiman.
    - Epidemiology and etiology
    - Diagnosis of hairy cell leukemia
      - Morphologic and Immunophenotypic Features
      - Electron Microscopy
    - Clinical manifestation
      - Clinical Features
      - Clinical Course and Complications
    - Differential diagnosis
      - Hairy Cell Leukemia-V
      - Splenic Marginal Zone Lymphoma (SMZL)
    - Treatment
      - Splenectomy
      - Interferon
      - Pentostatin
      - Cladribine
      - BL22 (anti-CD 22 recombinant immunotoxin)
    - Future prospects
    - References
  - Chapter 132. Mast Cell Leukemia and Other Mast Cell Neoplasms
    Richard M. Stone and Steven H. Bernstein.
    - Mast Cell Biology
      - Morphology
      - Ontogeny
      - Physiology
    - Mast Cell Leukemia and Other Mast Cell Neoplasms
      - Reactive Mastocytosis
      - Urticaria Pigmentosa
      - Cutaneous Mastocytosis (Urticaria Pigmentosa Only)
      - Systemic Mast Cell Disease
      - Systemic Mast Cell Disease with Another Hematological Malignancy
      - Pathophysiology of Neoplastic Mast Cell Proliferation
      - Mast Cell Leukemia
    - References
  - Chapter 133. Hodgkin's Disease
    Peter M. Mauch, Lawrence Weiss, and James O. Armitage.
    - History
      - Radiation Therapy
      - Chemotherapy
    - Epidemiology and Etiology
    - Pathology
      - Histopathology
      - Nature of the Reed-Sternberg Cell
      - Immunologic Abnormalities in Patients
      - Staging
    - Treatment of Stage I-II Hodgkin's Disease
      - Randomized Clinical Trials: MetaAnalysis of Trials from the 1970s
      - Prognostic Factors for Stage I-II Hodgkin's Disease
      - Risk of Occult Abdominal Involvement in Patients with Clinical Stage I or II Hodgkin's Disease
      - Long-Term Outcome of Treatment for Early Stage Hodgkin's Disease
      - Reduction of Staging or Treatment: Ongoing and Recently Completed Trials for Favorable Prognosis CS I-II Hodgkin's Disease
      - Combined Radiation Therapy and Chemotherapy
      - Chemotherapy Alone
      - Radiation Therapy Alone
      - Recommendations and Future Directions
      - Unfavorable Prognosis CS I-II Hodgkin's Disease
    - Treatment of Advanced Hodgkin's Disease
      - Radiation Therapy in Stage III-IV Hodgkin's Disease
      - Salvage Therapy
    - Summary
    - References
  - Chapter 134. Non-Hodgkin's Lymphomas
    Arnold S. Freedman and Lee M. Nadler.
    - Epidemiology and etiology
      - Incidence and Mortality
      - Exposures and Diseases Associated with Increased Risk of Developing NHL
    - Pathology, immunobiology, and natural history of NHL
      - Indolent Lymphomas
      - Aggressive Lymphomas
      - Highly Aggressive Lymphomas
    - Cytogenetics and molecular basis of NHL
      - Cytogenetics
      - Molecular Basis of NHLs
    - Differential diagnosis and sites of disease at presentation
    - Staging and disease detection
      - Diagnosis and Initial Evaluation
      - Immunologic and Molecular Studies
    - Disease parameters influencing prognosis and assessment of response
      - Clinical Prognostic Factors in Aggressive NHL
    - Therapeutic approaches according to REAL/WHO classification
      - Indolent lymphomas
      - Aggressive Lymphomas
      - High-Grade Lymphomas
      - Treatment of Recurrent Disease
    - New therapeutic approaches
    - References
  - Chapter 135. Mycosis Fungoides and the Sézary Syndrome
    Richard T. Hoppe and Youn H. Kim.
    - Epidemiology and Etiology
    - Pathology/Pathogenesis
    - Natural History
    - Diagnosis
    - Staging and Prognosis
    - Therapy
      - Current Therapies
      - Newer Therapies
    - References
  - Chapter 136. Plasma Cell Tumors
    Noopur Raje, Teru Hideshima, and Kenneth C. Anderson.
    - Multiple Myeloma
      - Diagnostic Criteria
      - Monoclonal Gammopathy of Unclear Significance
      - Epidemiology
      - Clinical Features
      - Laboratory Features
    - Biology
      - Cell Surface Phenotype
      - Cellular Origin of MM
      - Role of Adhesion Molecules in MM
      - Role of Growth Factors in MM
      - Role of Angiogenesis in MM
      - Molecular Pathogenesis of MM
    - Prognostic Factors
      - Staging Systems
      - Single Risk Factors
      - Complications
      - Neuropathies
      - Associated Diseases
    - Treatment
      - Conventional Therapy
      - Alpha-2b Interferon Therapy
      - Clinical Studies
      - Radiation Therapy
      - High-Dose Therapies
      - Future Directions
      - Evolution of a New Treatment Paradigm for MM
    - Other Plasma Cell Dyscrasias
      - Plasmacytomas
      - Immunoglobulin-M (IgM) Monoclonal Gammopathy
      - Waldenstrom Macroglobulinemia
      - Heavy-Chain Diseases
      - Amyloidosis
    - References
  - Chapter 137. The Chronic Myeloproliferative Disorders: Essential Thrombocythemia, Myelofibrosis with Myeloid Metaplasia, and Polycythemia Vera
    David P. Steensma and Ayalew Tefferi.
    - Essential Thrombocythemia
      - Epidemiology
      - Diagnosis
      - Pathogenesis
      - Clinical Manifestations
      - Prognosis and Therapy
      - Special Considerations: Pregnancy
    - Myelofibrosis with Myeloid Metaplasia
      - Epidemiology
      - Pathogenesis
      - Diagnosis
      - Clinical Manifestations
      - Prognosis
      - Therapy
    - Polycythemia Vera
      - Epidemiology
      - Pathogenesis
      - Clinical Features
      - Diagnosis
      - Prognosis
      - Treatment
    - References
- Section 35: Neoplasms in Aids
  - Chapter 138. Neoplasms in Acquired Immunodeficiency Syndrome
    David T. Scadden.
    - Epidemiology
      - Pre-HAART
      - Post-HAART
    - Kaposi Sarcoma
      - Viral Epidemiology
      - Clinical Manifestations
      - Pathology and Pathogenesis
      - Treatment
    - Non-Hodgkin Lymphoma
      - Epidemiology
      - Pathology and Pathogenesis
      - Clinical Setting
      - Clinical Manifestations
      - Clinical Approach
      - Treatment
      - Primary CNS Lymphoma
    - Hodgkin Disease
      - Epidemiology
      - Pathology and Pathogenesis
      - Clinical Features
      - Treatment
    - Squamous Cell Neoplasia
      - Epidemiology
      - Pathology and Pathogenesis
      - Clinical Presentation
      - Treatment
    - References
- Section 36: Unknown Primary Site
  - Chapter 139. Neoplasms of Unknown Primary Site
    John D. Hainsworth and F. Anthony Greco.
    - Poorly Differentiated Neoplasms
      - Immunoperoxidase Staining
      - Electron Microscopy
      - Chromosomal Analysis
    - Adenocarcinoma of Unknown Primary Site
      - Clinical Characteristics
      - Pathology
      - Diagnostic Evaluation
      - Treatment
    - Squamous Carcinoma of Unknown Primary Site
      - Squamous Cell Carcinoma Involving Cervical Lymph Nodes
    - Squamous Cell Carcinoma Involving Inguinal Lymph Nodes
      - Squamous Cell Carcinoma Metastatic to Other Sites
    - Poorly Differentiated Carcinoma of Unknown Primary Site
      - Pathologic Evaluation
      - Diagnostic Evaluation
      - Treatment
    - Neuroendocrine Carcinoma of Unknown Primary Site
      - Low-Grade Neuroendocrine Carcinoma
      - Small-Cell Carcinoma
      - Poorly Differentiated Neuroendocrine Carcinoma
    - Summary and Future Directions
    - References
Part VII Pediatric Oncology
- Section 37: Pediatric Oncology
  - Chapter 140a. Pediatric Oncology: Principles and Practice
    Gregory H. Reaman.
    - References
  - Chapter 140b. Incidence, Origins, Epidemiology
    Leslie L. Robison.
    - Acute leukemia
    - Central nervous system tumors
    - Lymphomas
    - Neuroblastoma
    - Retinoblastoma
    - Wilms tumor
    - Bone tumors
    - Rhabdomyosarcoma
    - References
  - Chapter 140c. Late Effects of Treatment of Cancer in Children and Adolescents
    Daniel M. Green.
    - Central Nervous System
    - Vision
    - Hearing
    - Teeth
    - Salivary Glands
    - The Heart
    - Lungs
    - Kidneys
    - The Bladder
    - the Liver
    - The Intestine
    - Musculoskeletal System
    - Endocrine System
      - Pituitary Gland
      - Thyroid Gland
      - Gonadal Function
    - Second Malignant Tumors
      - Genetic Factors
      - Treatment Factors
    - References
  - Chapter 141a. Childhood Acute Lymphoblastic Leukemia
    Paul S. Gaynon, Anne L. Angiolillo, Janet L. Franklin, and Gregory H. Reaman.
    - Heterogeneity
    - Induction
    - Morphological Response and Outcome
    - Minimal Residual Disease
    - Post Induction Intensification
    - Parenteral Methotrexate and Rescue
    - Presymptomatic Central Nervous System Therapy
    - Bone Marrow Transplantation in First Remission
    - Relapse
    - Conclusions
    - References
  - Chapter 141b. Acute Myeloid Leukemia in Children
    Richard Aplenc and Beverly Lange.
    - Epidemiology
    - Etiology
    - Classification and Diagnosis
    - Presentation
    - Therapy
    - Prognosis
    - Complications
    - Conclusion
    - References
  - Chapter 141c. Primary Central Nervous System Tumors of the Infant and Child
    Tobey J. MacDonald and Brian R. Rood.
    - General Epidemiology
    - Tumor Biology
      - Molecular Genetics
      - Angiogenesis
    - Treatment
      - Special Considerations in the Treatment of the Infant
      - Focal Radiotherapy Techniques
    - Astrocytic Tumors
      - Cerebellar Astrocytoma
      - Diencephalic Glioma
      - Low-Grade Cortical Glioma
      - High-Grade Cortical Glioma
      - Brain Stem Glioma
    - Embryonal Tumors
      - Primitive Neuroectodermal Tumor/Medulloblastoma
      - Supratentorial Primitive Neuroectodermal Tumor
      - Atypical Teratoid/Rhabdoid Tumor
    - Ependymal Tumors
      - Diagnosis
    - Germ Cell Tumors
      - Diagnosis
      - Treatment
    - References
  - Chapter 141d. Hodgkin's Disease
    James Nachman.
    - Biology
    - Clinical Presentation and Staging
    - Treatment
      - Chemotherapy
      - Radiotherapy
      - Late Effects of Treatment
    - Second Malignant Neoplasms
    - Cardiac Disease
    - Pulmonary Toxicity
    - Fertility Issues
    - Hypothyroidism
    - References
  - Chapter 141e. Non-Hodgkin Lymphoma in Children
    Mitchell S. Cairo, Elizabeth Raetz, and Sherrie Perkins.
    - Epidemiology
    - Pathology of Pediatric Non-Hodgkin Lymphoma
    - Clinical Presentation and Staging
    - General Principles of Treatment
      - B-Large-Cell Lymphoma
      - Burkitt and Burkitt-like Lymphoma in Children and Adolescents
      - Anaplastic Large-Cell Lymphoma
      - Lymphoblastic Lymphoma
    - Summary/Future Considerations
    - Acknowledgments
    - References
  - Chapter 142a. Less-Frequently Encountered Tumors of Childhood
    Carlos Rodriguez-Galindo and Alberto S. Pappo.
    - Retinoblastoma
      - Epidemiology
      - Clinical Forms
      - Biology
      - Genetic Counseling
      - Pathology
      - Clinical Manifestations
      - Evaluation
      - Staging
    - Principles of Treatment
      - Surgery
      - Focal Therapies
      - Radiotherapy
      - Chemotherapy
      - Treatment of Specific Situations
      - Long-term Effects
    - Germ Cell Tumors
      - Epidemiology
      - Pathology
      - Clinical Presentation
      - Treatment
    - Tumors of the Liver
      - Epidemiology and Etiology
      - Pathology and Molecular Genetic Abnormalities
      - Clinical Presentation and Abnormalities in Laboratory Findings
      - Treatment
    - Carcinomas and Melanoma
    - References
  - Chapter 142b. Renal Tumors of Childhood
    Paul E. Grundy, Michael L. Ritchey, Elizabeth J. Perlman, and John A. Kalapurakal.
    - Epidemiology
    - Molecular Biology and Genetics
    - Pathology
    - Clinical Presentation
    - Preoperative Evaluation
    - Staging
    - Therapy
      - Surgery
      - Radiation Therapy
      - Chemotherapy
      - Treatment of Recurrent Disease
    - Prognostic Factors
    - Long-Term Follow-Up
    - Acknowledgment
    - References
  - Chapter 142c. Neuroblastoma
    John M. Maris and Suzanne Shusterman.
    - Epidemiology
    - Molecular Pathogenesis
      - Genetic Predisposition
      - Neurotrophins
      - DNA Index
      - MYCN Amplification and Expression
      - Unbalanced Gain of 17q
      - Chromosomal Deletions
    - Pathology
    - Diagnosis and Staging
      - Signs and Symptoms
      - Paraneoplastic Syndromes
    - Diagnosis and Evaluation
      - Differential Diagnosis
      - Clinical and Laboratory Evaluation
    - Staging
      - Neuroblastoma Screening Studies
    - Prognostic Considerations
      - Clinical Variables
      - Biologic Variables
    - Principles of Initial Therapy
      - Surgery
      - Radiation Therapy
      - Chemotherapy
    - The Concept of Risk-Related Therapy
      - Treatment of Low-Risk Disease
      - Treatment of Intermediate-Risk Disease
      - Treatment of High-Risk Disease
    - Conclusions and Future Considerations
    - References
  - Chapter 142d. Soft-Tissue Sarcomas
    William H. Meyer.
    - Rhabdomyosarcoma
    - NRSTS
    - Future Research
    - Acknowledgments
    - References
  - Chapter 142e. Bone Tumors
    Richard G. Gorlick, Jeffrey A. Toretsky, Neyssa Marina, Suzanne L. Wolden, R. Lor Randall, Mark C. Gebhardt, Lisa A. Teot, and Mark Bernstein.
    - Osteosarcoma
      - Presentation
      - Epidemiology
      - Pathogenesis
      - Histology
      - Chemotherapy
      - Prognosis
      - Future Directions
    - Ewing sarcoma
      - Presentation
      - Differential diagnosis
      - Radiographic appearance
      - Epidemiology
      - Pathophysiology
      - Histologic findings
      - Molecular diagnosis
      - Chemotherapy
      - Localized disease
      - Toxicity
      - Second malignancy
      - Prognosis
      - Research studies and future directions
    - Chondrosarcoma
      - Mesenchymal chondrosarcomas
      - Dedifferentiated chondrosarcoma
    - Radiation oncology
      - Osteosarcoma
      - Chondrosarcoma and chordoma
      - ESFT
      - Primary lymphoma
      - Giant-cell tumors
      - Rare entities
      - Timing of radiation therapy
      - Acute side effects
      - Late effects
    - Surgery
      - Biopsy approaches
      - Treatment of malignant bone tumors
      - Types of reconstruction
      - Reconstruction as a function of location
      - Special considerations for the skeletally immature
      - Limb salvage versus amputation surgery
      - Adjuvant therapy considerations
      - Approach to other disease sites
    - Summary and Conclusions
    - References
  - Chapter 143a. Unique Pathologic Features of Childhood Cancer
    Kadria Sayed and David M. Parham.
    - Distinct morphologic features
    - Resemblance to embryonal tissue
    - Frequent occurrence of undifferentiated tumors
    - Infrequent association of childhood neoplasms with precursor lesions
    - Summary
    - References
  - Chapter 143b. Special Considerations for Young Adults and Older Adolescents
    W. Archie Bleyer and Karen Albritton.
    - Definition of Older Adolescent and Young Adult
    - Epidemiology
      - Incidence
      - Etiology
    - Diagnosis
      - Signs and Symptoms
      - Radiologic and Pathologic Considerations
    - Treatment
      - Choice of Treatment Setting and Specialist
      - Surgery
      - Radiation Therapy
      - Chemotherapy
      - Psychosocial and Supportive Care
    - Lack of Participation in Clinical Trials
    - Survival
      - Absolute Survival
      - Quality of Survival
    - Summary
    - References
Part VIII Complications
- Section 38: Complications of Cancer and its Treatment
  - Chapter 144. Cancer Anorexia and Cachexia
    Takao Ohnuma.
    - Incidence
    - Etiology
      - Anorexia and Early Satiety
      - Alimentary Tract Dysfunction
      - Biochemical and Metabolic Derangement
    - Manifestations of Cachexia
      - Clinical Manifestations ((Figure 144-2))
      - Laboratory Manifestations
    - Treatment of Cachexia
      - Supportive Care
      - Pharmacologic Management
      - Enteral and Parenteral Nutrition
    - Epilogue
    - References
  - Chapter 145. Antiemetic Therapy with Chemotherapy
    Richard Gralla.
    - Physiology and pharmacology in controlling emesis
    - Emetic problems
      - Acute chemotherapy-induced emesis
      - Delayed emesis
      - Anticipatory emesis
    - Control of emesis and patient characteristics
      - Alcohol intake history
      - Previous chemotherapy experience
      - Age
      - Gender
    - Treatment of acute chemotherapy-induced emesis
      - Serotonin receptor antagonists
      - Corticosteroids
      - Other antiemetic agents
    - Controlling emesis in special situations
      - Preventing delayed emesis
      - Preventing anticipatory emesis
      - Consecutive days of chemotherapy
    - Pharmacoeconomics, quality of life, and antiemetics
    - Conclusion
    - References
  - Chapter 146. Neurologic Complications
    Lisa M. DeAngelis and Jerome B. Posner.
    - Metastases
      - Spinal Metastases
      - Leptomeningeal Metastasis
      - Cranial and Peripheral Nerve Metastases
    - Nonmetastatic Complications
      - Complications of Cancer Therapy
      - Cerebrovascular Complications of Cancer
      - Metabolic Encephalopathy
      - Paraneoplastic Neurologic Syndromes
    - References
  - Chapter 147. Dermatologic Complications of Cancer Chemotherapy
    Narin Apisarnthanarax and Madeleine M. Duvic.
    - Alopecia
    - Stomatitis
    - Nail Reactions
    - Extravasation Reactions
    - Hyperpigmentation
    - Radiation-associated Reactions
    - Photosensitivity Reactions
    - Inflammation of Keratoses
    - Hypersensitivity Reactions
    - Acral Erythema
    - Neutrophilic Eccrine Hidradenitis
    - Eccrine Squamous Syringometaplasia
    - Cutaneous Eruption of Lymphocyte Recovery
    - Miscellaneous Reactions
      - Cytokines
      - Pegylated and Liposomal Modified Drugs
      - Nucleoside Analogues
      - Tyrosine Kinase Inhibitors
    - References
  - Chapter 148. Skeletal Complications
    Samuel Kenan and Jeffrey I. Mechanick.
    - Skeletal Metastases
      - Pathogenesis of Metastases
      - Patient Evaluation and Diagnostic Work-Up
      - Surgical Management
      - Metastatic Tumors to the Acetabulum
      - Metastatic Lesions to the Femur
      - Metastatic Lesions to the Scapula and Upper Extremity
      - Metastatic Lesions to the Spine
      - Medical Management of Bone Metastases
      - Hypercalcemia of Malignancy
    - Steroid-Induced Skeletal Complications
      - Corticosteroid-Induced Osteopenia
      - Corticosteroid-Induced Osteonecrosis
    - Methotrexate-Induced Osteopathy
    - Skeletal Complications Secondary to Radiation Therapy
    - References
  - Chapter 149. Hematologic Complications and Blood Bank Support
    Richard M. Kaufman and Kenneth C. Anderson.
    - Normal Hematopoiesis
    - Hematopoiesis
    - Causes of Pancytopenia
      - Disease Related
      - Chemotherapy Related
      - Gamma Radiation Related
      - Associated Processes
    - Abnormalities of Red Cells and Red Cell Support
      - Anemia
      - Red Cell Growth Factors
      - Red Cell Transfusion
      - Red Cell Products
    - Abnormalities of White Cells and White Cell Support
      - Leukocytosis
      - Leukopenia
      - Associated Processes
      - Leukocyte Transfusion
      - Clinical Studies
      - Leukocyte Collection and Administration
      - Myeloid Growth Factors
    - Abnormalities of Platelets and Platelet Support
      - Thrombocytosis
      - Thrombocytopenia
      - Abnormalities in Platelet Function
      - Platelet Transfusion Support
      - Single- and Multiple-Donor Platelets
      - Indications for Therapeutic and Prophylactic Platelet Transfusion
      - Clinical and Laboratory Assessment of the Effectiveness of Platelet Transfusion
      - Alloimmunization
      - Platelet Alloantigens
      - Alternatives to Platelet Transfusion
    - Other Therapeutic Modalities
      - Transfusion of Fresh Frozen Plasma
      - Therapeutic Pheresis
    - Effects of Transfusion on the Immune System
      - Alloimmunization
      - Immunosuppression
    - Transfusion-Associated Graft-Versus-Host Disease
      - Historic Perspective
      - Definition of Those at Risk
      - Strategies for Prevention
      - Conclusions and Recommendations
    - Transfusion-Related Infectious Diseases (Table 149-6)
      - Hepatitis B
      - Non-A Non-B Hepatitis
      - Hepatitis GB Virus
      - Cytomegalovirus
      - Bacterial Sepsis
      - Acquired Immune Deficiency Syndrome
      - Human T-Cell Lymphotrophic Virus Type I (HTLV-1)
      - Other Viruses
      - Parasitic Diseases
      - Creutzfeldt-Jakob Disease
    - Future Directions in Blood Component Therapy
      - Increased Role in Primary Treatment of Cancer (Table 149-8)
      - Hematopoietic Stem Cell Transplantation
      - Peripheral Blood Stem Cell Autotransplantation
      - Leukopoor/Single-Donor Blood Components
    - Conclusion
    - References
  - Chapter 150. Coagulopathic Complications of Cancer Patients
    Maria T. DeSancho and Jacob H. Rand.
    - Physiology of Normal Hemostasis
    - Relationship of Coagulation System and Cancer
    - Bleeding Disorders
      - Thrombocytopenia
      - Thrombocytopathies
      - Coagulation Factor Deficiencies
      - Amyloidosis
      - Drug Effects (l-Asparaginase)
      - Acute Promyelocytic Leukemia
      - Thrombotic Complications
    - Anticancer Effects of Anticoagulation Treatment
    - Heparin-Induced Thrombocytopenia
      - Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome
      - Arterial Thrombosis and Nonbacterial Thrombotic Endocarditis
      - Disseminated Intravascular Coagulation
    - Novel Drugs for Treatment of Bleeding and Thrombotic Disorders
      - Factor Xa Inhibitors: Synthetic Pentasaccharide
      - Oral Direct Thrombin Inhibitors: H376/95 (Ximelagatran)
    - Summary
    - References
  - Chapter 151. Urologic Complications
    Christopher J. Logothetis, Vasily Assikis, and Jose E. Sarriera.
    - Complications Resulting from Primary Cancer Progression
      - Urinary Tract Obstruction
      - Ureteral Obstruction
      - Bladder Outlet Obstruction
      - Lower Urinary Tract Obstruction
      - Diagnostic Studies
    - Algorithm for the Management of Urinary Obstruction
      - Hemorrhagic Cystitis
      - Recurrence of Tumor
      - Treatment
    - Radiation Nephritis
    - Diagnosis, Treatment, and Prevention of Nephrotoxicity of Cancer Therapeutic Agents
      - Cisplatin
      - Methotrexate
      - Nitrosoureas
      - Mitomycin C
      - Immunologic Agents
      - Other Agents
    - Monitoring for Drug-Induced Nephrotoxicity
    - References
  - Chapter 152. Cardiac Complications
    Michael S. Ewer, Robert S. Benjamin, and Edward T.H. Yeh.
    - Evaluation of the cardiovascular system in the cancer patient
      - Primary medical evaluation, routine laboratory evaluation, and special imaging
    - Metastatic involvement of cardiac structures
      - Malignant pericardial effusion
      - Metastatic Involvement of the Myocardium
    - Cardiac effects of mediator release from tumors
      - Carcinoid heart disease
      - High-Output States
      - Cardiac Amyloidosis
    - Cardiac dysrhythmia in the cancer patient
      - Categories of dysrhythmia: Primary (Structural) versus Secondary (Metabolic) Etiologies
      - Treatment of Cardiac Rhythm Disturbances
    - Cardiac complications of cancer treatment
      - Chemotherapeutic agents
      - Effects of Irradiation of the Heart
    - References
  - Chapter 153. Respiratory Complications
    John C. Ruckdeschel, John Greene, K. Eric Sommers, and Karen K. Fields.
    - Respiratory infections in patients with cancer
      - Nonneutropenia Phase (Pre- and PostTherapy)
      - Neutropenia Phase
      - Post-Engraftment Phase (Following Allogeneic Stem Cell Transplantation)
    - Surgical complications causing dyspnea in cancer patients
      - Pleural Effusion
      - Empyema/Bronchopleural Fistula
      - Phrenic and Recurrent Laryngeal Nerve Palsy
      - Chylothorax
      - Endobronchial Lesions
      - Tracheoesophageal Fistula
      - Pericardial Effusions
      - Pulmonary Complications of Ionizing Radiation
      - Respiratory Complications Associated with Transplant
      - Chemotherapy Plus total Body Irradiation
      - Pulmonary Complications Associated with Transplant
    - References
  - Chapter 154. Liver Function and Hepatotoxicity in Cancer
    Laurie D. DeLeve.
    - Alterations in Hepatic Metabolism of Drugs
      - Drug Interactions
      - Underlying Liver Disease
      - Aging
      - Gender
      - Nutrition
      - Genetic Polymorphisms
    - Liver Toxicity and Hematopoietic Stem Cell Transplantation
      - Sinusoidal Obstruction Syndrome (Hepatic Venoocclusive Disease)
      - Nodular Regenerative Hyperplasia
      - Cyclosporine-Induced Cholestasis
    - Hepatotoxicity by Anticancer Therapy
      - Diagnosis of Hepatotoxicity
      - Selected Anticancer Drugs and Modalities
    - Conclusions
    - References
  - Chapter 155. Gastrointestinal Complications
    Frank A. Sinicrope.
    - Esophageal Carcinoma
      - Malignant Dysphagia
      - Esophageal Dilation
      - Laser Therapy
      - Esophageal Prosthesis
    - Esophagitis
      - Infectious Esophagitis
    - Upper Gastrointestinal Bleeding
    - Pseudomembranous Colitis
    - Typhlitis
      - Clinical Presentation and Diagnosis
      - Management
    - Ileus and Bowel Obstruction
      - Clinical Manifestations
      - Etiology
      - Diagnosis
      - Treatment
    - Acute Colonic Pseudoobstruction
      - Pathogenesis
      - Clinical Presentation and Diagnosis
      - Treatment
    - Diarrhea Chemotherapy and Radiation-Related Diarrhea
      - Diarrhea in Patients Undergoing Hematopoietic Cell Transplantation
      - Other Causes of Diarrhea
      - Treatment
    - Biliary Obstruction
      - Clinical Manifestations
      - Diagnosis
      - Treatment
    - Hepatic Complications of Bone Marrow Transplantation
      - Hepatic Venoocclusive Disease
      - Acute Graft-versus-Host Disease
      - Infectious Hepatitis
    - Ascites
      - Clinical Manifestations
      - Diagnosis
      - Treatment
    - Acute Pancreatitis
    - Radiation Coloproctitis and Proctitis
    - Anorectal Complications
    - References
  - Chapter 156. Oral Complications
    Stephen T. Sonis and Joseph W. Costa, Jr.
    - Pretreatment Assessment
      - Timing of Assessment
    - Oral Complications of Radiotherapy
      - Mucositis
      - Xerostomia
      - Osteoradionecrosis
    - Oral Complications of Cancer Chemotherapy
      - Risk Factors
      - Fungal infections
      - Viral Infections
      - Bacterial Infections
    - Oral Complications Associated with Bone Marrow Transplantation
      - Mucositis
      - Infection
      - Graft-Versus-Host Disease
    - References
  - Chapter 157. Gonadal Complications
    Catherine E. Klein.
    - The Hypothalamic-Pituitary-Gonadal Axis
    - Historical Background
    - Preclinical Studies
    - Effects of Chemotherapy on Gonadal Function
      - Effects in Boys
      - Effects in Men
      - Effects in Prepubertal Girls
      - Effects in Women
      - Fertility Following High-dose Chemotherapy
    - Effects of Radiation Therapy on Gonadal Function
      - Effects in Men
      - Effects in Women
    - Protective Measures
      - Protection for Men
      - Protection for Women
      - Protection for children
    - Outcomes of Pregnancy
      - Chemotherapy
      - Radiation Therapy
    - Psychosocial Issues
    - References
  - Chapter 158. Endocrine Complications and Paraneoplastic Syndromes
    Sai-Ching Jim Yeung and Robert F. Gagel.
    - Endocrine Complications
      - Hypothalamic-Pituitary Dysfunction
      - Thyroid Disorders
      - Diabetes Mellitus
      - Metabolic Bone Diseases
      - Adrenal Diseases
      - Disorders of Growth Hormone Secretion and Growth
      - Disorders of Electrolyte/Mineral Metabolism
      - Disorders of Lipid Metabolism
      - Sexual Dysfunction
    - Endocrine Paraneoplastic Syndromes (“Ectopic” Hormone Production)
      - Defined Clinical Syndromes
      - Other Ectopic Hormone Syndromes
    - References
  - Chapter 159. Secondary Cancers: Incidence, Risk Factors, and Management
    Susan R. Rheingold, Alfred I. Neugut, and Anna T. Meadows.
    - Incidence of Secondary Cancer
    - Clinical Characteristics
    - Shared Environmental Risk Factors
      - Tobacco
      - Diet and Hormones
      - Other Shared Risk Factors
    - Genetic Risk Factors
      - Retinoblastoma
      - Neurofibromatosis
      - Li-Fraumeni Syndrome
      - Syndromes of Inherited Colon Cancer
      - Familial Breast Cancer
      - Multiple Endocrine Neoplasia
      - Skin-Related Syndromes
      - Other Syndromes Associated with Cancer Susceptibility
    - Therapy-Related Secondary Cancers
      - Ionizing Radiation
      - Chemotherapy
      - Hodgkin's Disease
      - Retinoblastoma
      - Acute Lymphocytic Leukemia
      - Wilms Tumor
      - Pediatric Sarcomas
      - Upper Aerodigestive Tract Cancers
      - Breast Cancer
      - Prostate Cancer
      - Testicular Cancer
      - Pancreas/Gastric Cancer
      - Colorectal Cancer
      - Endometrial/Ovarian Cancer
      - Skin Cancer
    - Conclusion
    - References
- Section 39: Infection in the Cancer Patient
  - Chapter 160. Infections in Patients with Cancer
    Kenneth V.I. Rolston and Gerald P. Bodey.
    - Factors Responsible for Increased Susceptibility to Infections
      - Neutropenia
      - Cellular Immune Dysfunction
      - Humoral Immune Dysfunction
      - Bone Marrow Transplantation
      - Local Factors
      - Intravascular Devices
      - Splenectomy
      - Chemotherapeutic Agents
    - Bacterial Infections
      - Enterobacteriaceae
      - Pseudomonas aeruginosa
      - Stenotrophomonas
      - Acinetobacter Species
      - Salmonella Species
      - Streptococcus Species
      - Staphylococcus Species
      - Enterococcus Species
      - Listeria monocytogenes
      - Mycobacterial Species
      - Legionella pneumophila
    - Fungal Infections
      - Candida Species
      - Aspergillus Species
      - Cryptococcus Species
      - Other Opportunistic Fungi
      - Empiric Therapy
    - Viral Infections
      - HSV
      - VZV
      - CMV
      - HHV-6
      - EBV
      - Community Respiratory Viral Infections
      - Hepatitis Viruses
      - Progressive Multifocal Leukoencephalopathy
    - Protozoal Infections
      - P. carinii
      - T. gondii
    - Other Parasitic Infections
    - Abdominal Infection
    - Perianal Infections
    - Skin Infections
    - Therapy of Infections in Neutropenic Patients
      - General Principles
      - Patient Evaluation
      - Initial Antibiotic Therapy
      - Low-Risk Patients
      - Duration of Therapy
      - Fever of Unexplained Origin
      - Other Therapeutic Modalities
    - Infection Prevention
      - Antimicrobial Prophylaxis
      - Antifungal and Antiviral Prophylaxis
      - Isolation
    - Perspectives
    - References
- Section 40: Oncologic Emergencies
  - Chapter 161. Oncologic Emergencies
    Sai-Ching Jim Yeung and Carmen P. Escalante.
    - Approach to Acutely Ill Cancer Patients
    - Circulatory Oncologic Emergencies
      - Sudden Cardiopulmonary Arrest
      - Arrhythmia
      - Tumor Lysis Syndrome
      - Pericardial Tamponade
      - Acute Hemorrhage
      - Carotid Artery Rupture
      - Superior Vena Cava Syndrome
    - Respiratory Oncologic Emergencies
      - Massive Hemoptysis
      - Massive Pleural Effusion
      - Acute Airway Obstruction
      - Pneumothorax
      - Pulmonary Embolism
    - Neurologic Oncologic Emergencies
      - Spinal Cord Compression
      - Brain Herniation
      - Status Epilepticus
    - Other Oncologic Emergencies
      - Perforated Bowel
      - Neutropenic Fever
      - Anaphylaxis to Chemotherapy Drugs
      - Systemic Reactions to Cytokines and Monoclonal Antibodies
    - References
Part IX Informatics
- Section 41: Oncology and Informatics
  - Chapter 162. Oncology Informatics
    Edward P. Ambinder.
    - Healthcare Policy and Information Technology
    - Medical and Oncologic Informatics
    - Overview of Computers
      - Personal Digital Assistant and Table PCs
      - Networks
    - Internet
    - Information Management
      - Medical Education
      - Computerized Patient Records
      - Clinical Data Systems
      - Clinical Trials
      - Clinical Practice Guidelines
      - Information Refinement
      - Unified Medical Language System
      - Clinical Laboratory and Testing Standards
      - Text Retrieval
    - Major Internet Resources of Interest to the Oncologist
    - Cancer.gov
      - CANCERLIT
      - MEDLINE
      - PubMed Central
      - Biosis
      - Embase
      - National Cancer Database
      - ISI Journal Citation Reports
      - Physician Data Query
      - The Physician's Information and Education Resource
      - SEER
      - CCRIS
    - Clinical and Research Uses of Computers in Medical Oncology
      - Computer-Generated Media
      - Document Imaging and Image Processing
      - Presentation Devices
      - Scanners
      - Optical Character Recognition
      - Presentation Software
      - Data Acquisition and Instrument Control
      - Bioinformatics
      - Statistics
    - References

An approved publication of the American Cancer Society

Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs and drug dosages, is in accord with the accepted standard and practice at the time of publication. However, since research and regulation constantly change clinical standards, the reader is urged to check the product information sheet included in the package of each drug, which includes recommended doses, warnings, and contraindications. This is particular important with new or infrequently used drugs. Any treatment regimen, particularly one involving medication, involves inherent risk that must be weighed on a case-by-case basis against the benefits anticipated. The reader is cautioned that the purpose of this book is to inform and enlighten; the information contained herein is not intended as, and should not be employed as, a substitute for individual diagnosis and treatment.

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Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.

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