Holland, Frei cancer medicine 6

Front Matter Title Editors Copyright Notice Contributors Preface Contents Part I - Cardinal Manifestations Part II - Scientific Foundations Part III - Cancer Diagnosis Part IV - Therapeutic Modalities Part V - Multidisciplinary Management Part VI - Cancer Management Part VII - Pediatric Oncology Part VIII - Complications Part IX - Informatics Part I - Cardinal Manifestations 1. Cardinal Manifestations of Cancer Part II - Scientific Foundations Section 1 - CANCER BIOLOGY 2. Molecular Biology, Genomics, and Proteomics INTRODUCTION OVERVIEW: GENE STRUCTURE GENERAL TECHNIQUES GENE ANALYSIS: DNA GENE EXPRESSION: MRNA TRANSCRIPT ANALYSIS GENE EXPRESSION: PROTEIN ANALYSIS REFERENCES FIGURES 3. Cell Proliferation and Differentiation INTRODUCTION PROLIFERATION APOPTOSIS AND PROLIFERATION DIFFERENTIATION ACKNOWLEDGMENT REFERENCES TABLES FIGURES 4. Apoptosis and Cancer INTRODUCTION APOPTOSIS CAUSED BY CASPASES CASPASE ACTIVATION PATHWAYS: AN OVERVIEW PROTEIN DOMAINS INVOLVED IN APOPTOSIS REGULATION SIGNAL TRANSDUCTION AND APOPTOSIS DYSREGULATION IN CANCER THERAPEUTIC OPPORTUNITIES FROM APOPTOSIS RESEARCH ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 5. Growth Factors and Signal Transduction In Cancer INTRODUCTION BACKGROUND GROWTH FACTOR RECEPTORS WITH TYROSINE KINASE ACTIVITY CLASSIFICATION OF GROWTH FACTORS AND THEIR RECEPTORS ABNORMALITIES ASSOCIATED WITH GROWTH FACTORS IN CANCER CELLS ABERRATIONS AFFECTING GROWTH FACTOR RECEPTORS IN TUMOR CELLS SIGNALING PATHWAYS OF TYROSINE KINASE RECEPTORS IMPLICATIONS FOR CANCER THERAPY REFERENCES TABLES FIGURES 6. Oncogenes INTRODUCTION DISCOVERY AND IDENTIFICATION OF ONCOGENES MECHANISMS OF ONCOGENE ACTIVATION ONCOGENES IN THE INITIATION AND PROGRESSION OF NEOPLASIA SUMMARY AND CONCLUSIONS REFERENCES TABLES FIGURES 7. Tumor-Suppressor Genes INTRODUCTION GENETIC BASIS FOR TUMOR DEVELOPMENT SOMATIC CELL GENETIC STUDIES OF TUMORIGENESIS RETINOBLASTOMA—A PARADIGM FOR TUMOR-SUPPRESSOR GENE FUNCTION THE P53 GENE THE INK4A LOCUS AND THE P16INK4A AND P19ARF GENES THE APC GENE BRCA1 AND BRCA2 GENES WT1 GENE NF1 AND NF2 GENES VHL GENE DNA REPAIR PATHWAY GENES CANDIDATE TUMOR-SUPPRESSOR GENES SUMMARY REFERENCES TABLES FIGURES 8. Recurring Chromosome Rearrangements in Human Cancer INTRODUCTION MYELOPROLIFERATIVE DISORDERS ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROME ASSOCIATED WITH PRIOR CYTOTOXIC THERAPY HOW AND WHY RECURRING CHROMOSOMAL ABNORMALITIES OCCUR ACKNOWLEDGMENT REFERENCES TABLES FIGURES 9. Biochemistry of Cancer INTRODUCTION HISTORICAL PERSPECTIVES WHAT MAKES A CANCER CELL A CANCER CELL? ACKNOWLEDGMENTS REFERENCES TABLES 10. Invasion and Metastases INTRODUCTION TUMOR-HOST AND TUMOR-STROMAL INTERACTIONS ADHESION PROTEOLYSIS TUMOR CELL MIGRATION ANGIOGENESIS GENETIC REGULATION OF INVASION AND METASTASIS NOVEL TECHNOLOGIES ADVANCE IDENTIFICATION OF METASTASIS AND INVASION-PROMOTING GENES AND GENE PRODUCTS INVASION AS A THERAPEUTIC MOLECULAR TARGET SUMMARY REFERENCES TABLES FIGURES 11. Tumor Angiogenesis INTRODUCTION HISTORIC BACKGROUND BEGINNING OF ANGIOGENESIS RESEARCH ACKNOWLEDGMENTS REFERENCES TABLES FIGURES Section 2 - CANCER IMMUNOLOGY 12. Tumor Antigens INTRODUCTION 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 SUMMARY ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 13. Tumor Markers and Immunodiagnosis INTRODUCTION 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 NEW APPROACHES AND TECHNOLOGIES CONCLUSION ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 14. Effectors of Immunity and Rationale for Immunotherapy INTRODUCTION ANTITUMOR EFFECTOR CELLS IN HUMANS T LYMPHOCYTES ASSESSMENT OF T-CELL EFFECTORS IN PATIENTS WITH CANCER IMPLICATIONS OF EFFECTOR CELL DYSFUNCTION IN CANCER RATIONALE FOR IMMUNOTHERAPY OF CANCER REFERENCES FIGURES 15. Tumor-Associated Immunodeficiency and Implications for Tumor Development and Prognosis INTRODUCTION DOCUMENTATION OF IMMUNE SUPPRESSION IN CANCER PATIENTS MECHANISMS OF IMMUNOSUPPRESSION CONCLUSIONS REFERENCES TABLES FIGURES Section 3 - CANCER ETIOLOGY 16. Genetic Predisposition to Cancer INTRODUCTION GENETIC BASIS OF CANCER SYNDROMES CANCER-ASSOCIATED GENODERMATOSES OTHER CANCERS WITH FAMILIAL CLUSTERINGS CLINICAL TRANSLATION CONCLUSIONS/FUTURE DIRECTIONS REFERENCES TABLES FIGURES 17. Chemical Carcinogenesis INTRODUCTION MULTISTAGE CARCINOGENESIS GENE-ENVIRONMENT INTERACTIONS AND INTERINDIVIDUAL VARIATION 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 TABLES FIGURES 18. Hormones and the Etiology of Cancer INTRODUCTION BREAST CANCER ENDOMETRIAL CANCER OVARIAN CANCER PROSTATE CANCER ADOLESCENT AND YOUNG ADULT GENITAL CANCER CERVICAL CANCER THYROID CANCER OSTEOSARCOMA CONCLUSION REFERENCES TABLES FIGURES 19. Ionizing Radiation INTRODUCTION DEVELOPMENT OF RADIATION INJURY PRINCIPAL CELLULAR AND TISSUE EFFECTS OF RADIATION MOLECULAR MECHANISMS EXPERIMENTAL RADIATION-INDUCED CARCINOGENESIS HUMAN EPIDEMIOLOGIC STUDIES RISK ASSESSMENT ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 20. Ultraviolet Radiation Carcinogenesis INTRODUCTION HISTORICAL PERSPECTIVE EPIDEMIOLOGY GENETIC FACTORS IN SKIN CARCINOGENESIS XERODERMA PIGMENTOSUM COCKAYNE SYNDROME TRICHOTHIODYSTROPHY CARCINOGENESIS REFERENCES TABLES FIGURES 21. Physical Carcinogens INTRODUCTION KNOWN PHYSICAL CARCINOGENS MECHANISMS OF CARCINOGENESIS ELECTROMAGNETIC FIELDS TRAUMA CONCLUSIONS REFERENCES TABLES FIGURES 22. Tumor Viruses INTRODUCTION CLASSIFICATION STRUCTURE REPLICATION CYCLE MECHANISMS OF ONCOGENESIS ENDOGENOUS RETROVIRUSES RETROVIRAL VECTORS AND GENE THERAPY CONCLUSIONS REFERENCES TABLES FIGURES 23. Herpesviruses INTRODUCTION PROPERTIES OF HERPESVIRUSES ONCOGENIC FEATURES OF HERPESVIRUSES EPSTEIN-BARR VIRUS: AN ONCOGENIC HUMAN HERPESVIRUS HUMAN HERPESVIRUS 8 AND MALIGNANCIES VIRAL PROTEINS CLINICAL ASPECTS ONCOGENIC POTENTIAL OF OTHER HUMAN HERPESVIRUSES REFERENCES TABLES 24. Papillomaviruses and Cervical Neoplasia INTRODUCTION DEFINITIONS, TISSUE SPECIFICITY, AND MECHANISMS OF INFECTION AND TRANSFORMATION HPV AND HUMAN GENITAL NEOPLASIA REFERENCES TABLES FIGURES 25. Hepatitis Viruses INTRODUCTION HEPATITIS B VIRUS HEPATITIS C VIRUS HEPATITIS D VIRUS HEPATITIS A VIRUS HEPATITIS E VIRUS HEPATITIS F, G, AND TT VIRUSES REFERENCES TABLES 26. Parasites INTRODUCTION SCHISTOSOMIASIS AND CANCER OF THE BLADDER SCHISTOSOMIASIS AND CANCER OF OTHER SITES EAST ASIAN DISTOMIASIS MALARIA AMERICAN BURKITT LYMPHOMA CANCER IN ANIMALS REFERENCES TABLES FIGURES Section 4 - CANCER EPIDEMIOLOGY, PREVENTION AND SCREENING 27. Cancer Epidemiology INTRODUCTION MEASURES OF DISEASE OCCURRENCE CANCER SURVEILLANCE SURVIVAL OF PATIENTS WITH CANCER STUDIES OF CANCER ETIOLOGY DESCRIPTIVE STUDIES ANALYTIC EPIDEMIOLOGY MEASURES OF ASSOCIATION CASE-CONTROL STUDIES WHAT CONSTITUTES "PROOF" IN EPIDEMIOLOGIC STUDIES? IARC CLASSIFICATION OF CARCINOGENS SUMMARY REFERENCES TABLES FIGURES 28. Prevention of Tobacco-Related Cancer INTRODUCTION PHYSIOCHEMICAL COMPOSITION OF TOBACCO SMOKE CARCINOGENIC AND GENOTOXIC EFFECTS OF TOBACCO CONSTITUENTS GENETIC VARIATION IN CANCER SUSCEPTIBILITY APPROACHES FOR SMOKING CESSATION PREVENTION OF TOBACCO USE SUMMARY REFERENCES TABLES 29. Nutrition in the Etiology and Prevention of Cancer INTRODUCTION METHODOLOGIC ISSUES IN DIET, NUTRITION, AND CANCER STUDIES PUBLIC HEALTH GUIDELINES FOR CANCER PREVENTION SUMMARY OF RESEARCH EFFORTS FOCUSING ON SPECIFIC CANCERS CURRENT RESEARCH SURVIVORSHIP: DIET AND NUTRITIONAL GUIDANCE DURING AND FOLLOWING CANCER TREATMENT REFERENCES TABLES FIGURES 30. Chemoprevention of Cancer INTRODUCTION AGENTS FOR CHEMOPREVENTION AND THEIR MECHANISM OF ACTION CHEMOPREVENTION TRIALS CHEMOPREVENTION AND OVERALL CANCER INCIDENCE REFERENCES TABLES 31. Cancer Screening and Early Detection INTRODUCTION KEY CRITERIA IN THE DECISION TO SCREEN METHODOLOGIC ISSUES IN THE EVALUATION OF EARLY DETECTION PROGRAMS BREAST CANCER COLORECTAL CANCER LUNG CANCER PROSTATE CANCER TESTICULAR CANCER CERVICAL CANCER ENDOMETRIAL CANCER OVARIAN CANCER MELANOMA AND NONMELANOMA SKIN CANCER ORAL CANCER THE CANCER-RELATED CHECKUP CONCLUSION REFERENCES TABLES FIGURES Section 5 - CLINICAL TRIALS AND OUTCOMES ASSESSMENT 32. Theory and Practice of Clinical Trials INTRODUCTION TYPES OF CLINICAL TRIALS PLANNING CLINICAL TRIALS 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 STATISTICAL MODELS META-ANALYSIS FALSIFICATION OF DATA REFERENCES TABLES FIGURES 33. Statistical Innovations in Cancer Research INTRODUCTION BAYESIAN UPDATING ANALYSIS ISSUES DECISION ANALYSIS AND CHOOSING SAMPLE SIZE ADAPTIVE DESIGNS OF CLINICAL TRIALS AUXILIARY VARIABLES, BIOMARKERS, AND BIOLOGICAL AGENTS ACKNOWLEDGEMENTS: REFERENCES TABLES FIGURES 34. Outcomes Assessment INTRODUCTION HISTORICAL PERSPECTIVE OUTCOME MEASURES STUDY DESIGNS OUTCOMES STUDIES IN ONCOLOGY OUTCOMES MANAGEMENT SUMMARY REFERENCES TABLES FIGURES Part III - Cancer Diagnosis Section 6 - CANCER PATHOLOGY 35. Principles of Cancer Pathology INTRODUCTION TUMOR STRUCTURE AND TUMOR STROMA GENERATION ROLE OF THE SURGICAL PATHOLOGIST IN THE DIAGNOSIS AND MANAGEMENT OF THE CANCER PATIENT SUMMARY AND CONCLUSIONS REFERENCES TABLES FIGURES Section 7 - IMAGING 36. Principles of Imaging INTRODUCTION REFERENCES 36a. Imaging Cancer of Unknown Primary Site INTRODUCTION REFERENCES FIGURES 36b. Imaging Neoplasms of the Central Nervous System, Head, and Neck INTRODUCTION CENTRAL NERVOUS SYSTEM HEAD AND NECK LYMPHADENOPATHY EXTRAMUCOSAL MASSES CONCLUSION REFERENCES 36c. Imaging Neoplasms of the Thorax INTRODUCTION LUNG CANCER MEDIASTINAL MASSES MALIGNANT PLEURAL MESOTHELIOMA CONCLUSION REFERENCES FIGURES 36d. Imaging Neoplasms of the Abdomen and Pelvis INTRODUCTION 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 FIGURES 36e. Imaging of Musculoskeletal Neoplasms INTRODUCTION REFERENCES FIGURES 36f. Imaging the Breast INTRODUCTION TYPES OF MAMMOGRAPHY STANDARDIZED MAMMOGRAPHY REPORTING THE NORMAL MAMMOGRAM THE ABNORMAL MAMMOGRAM MAMMOGRAPHY FOR PREOPERATIVE PLANNING MAMMOGRAPHY OF THE POSTSURGICAL BREAST ULTRASONOGRAPHY IMAGING-GUIDED NEEDLE BIOPSY OF THE BREAST OTHER BREAST IMAGING MODALITIES REFERENCES TABLES FIGURES 36g. Ultrasonography: Its Role in Oncologic Imaging INTRODUCTION RECENT ADVANCES TUMOR DETECTION AND CHARACTERIZATION SMALL PARTS SCANNING THE ABDOMINAL ORGANS GYNECOLOGIC ORGANS PROSTATIC AND TRANSRECTAL SONOGRAPHY CENTRAL NERVOUS SYSTEM ULTRASONOGRAPHY INTRAOPERATIVE ULTRASONOGRAPHY CONCLUSION REFERENCES FIGURES 36h. Radionuclide Imaging in Cancer Medicine INTRODUCTION SINGLE-PHOTON TECHNIQUES POSITRON EMISSION TOMOGRAPHY CONCLUSION REFERENCES FIGURES 36i. Perspectives in Imaging: Present and Future Prospects of Clinical Molecular Imaging INTRODUCTION CLINICAL MOLECULAR IMAGING TODAY: PET AND SPECT ON THE HORIZON: IMAGING GENE EXPRESSION IN VIVO WITH REPORTER GENES ON THE HORIZON: CLINICAL MOLECULAR IMAGING WITH OPTICAL AND MRI SUMMARY ACKNOWLEDGMENTS REFERENCES FIGURES 37. Interventional Radiology for the Cancer Patient INTRODUCTION INTRA-ARTERIAL THERAPY BIOPSY INTRATUMORAL GENE THERAPY MECHANICAL DEVICES REFERENCES FIGURES Part IV - Therapeutic Modalities Section 8 - SURGICAL ONCOLOGY 38. Principles of Surgical Oncology INTRODUCTION HISTORICAL CONSIDERATIONS THE CONTEMPORARY ROLE OF SURGICAL ONCOLOGY COMBINED MODALITY THERAPY SURGICAL COMPONENTS OF CANCER MANAGEMENT SPECIAL SITUATIONS nbsp; REFERENCES TABLES FIGURES Section 9 - RADIATION ONCOLOGY 39. Principles of Radiation Oncology INTRODUCTION PHYSICAL BASIS OF RADIATION THERAPY TREATMENT PLANNING AND DELIVERY BIOLOGIC BASIS OF RADIATION THERAPY FUTURE DIRECTIONS REFERENCES TABLES FIGURES 40. Photodynamic Therapy of Cancer INTRODUCTION HISTORY OVERVIEW BASICS OF LIGHT AND PDT-RELATED PHOTOCHEMISTRY PHOTOSENSITIZERS PHOTOSENSITIZER TRANSPORT AND DISTRIBUTION BIOLOGIC MECHANISMS OF PDT PHOTODYNAMIC THERAPY DOSIMETRY PHOTODYNAMIC THERAPY WITH TARGETED MOLECULAR DELIVERY SYSTEMS PERSPECTIVES ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 41. Hyperthermia INTRODUCTION THE BIOLOGY OF HYPERTHERMIA HYPERTHERMIA AND PHYSIOLOGY PHYSIOLOGIC APPROACHES TO ENHANCE THERMAL CYTOTOXICITY HYPERTHERMIA AND CHEMOTHERAPY HYPERTHERMIA PHYSICS CLINICAL HYPERTHERMIA ACKNOWLEDGMENTS REFERENCES TABLES FIGURES Section 10 - MEDICAL ONCOLOGY 42. Principles of Medical Oncology INTRODUCTION 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 TABLES Section 11 - CHEMOTHERAPY 43. Cytokinetics INTRODUCTION CELL PROLIFERATION GROWTH CURVE ANALYSIS CONCLUSION REFERENCES FIGURES 44. Principles of Dose, Schedule, and Combination Therapy INTRODUCTION DOSE SCHEDULE OF DRUG ADMINISTRATION COMBINATION CHEMOTHERAPY REFERENCES TABLES FIGURES 45. Preclinical and Early Clinical Development of New Anticancer Agents INTRODUCTION EVOLUTION OF THE DISCOVERY PROCESS PREPARATION OF AGENTS FOR CLINICAL TRIALS EARLY CLINICAL TRIALS REFERENCES TABLES FIGURES 46. Pharmacology INTRODUCTION GENERAL MECHANISMS OF DRUG ACTION PRINCIPLES OF PHARMACOKINETICS PRINCIPLES OF PHARMACODYNAMICS REFERENCES TABLES FIGURES 47. Regional Chemotherapy INTRODUCTION PHARMACOKINETIC RATIONALE FOR REGIONAL CHEMOTHERAPY MATHEMATICAL MODEL DESCRIBING REGIONAL ANTICANCER DRUG DELIVERY THEORETICAL CONCERNS WITH REGIONAL ANTINEOPLASTIC DRUG THERAPY PRACTICAL ISSUES ASSOCIATED WITH REGIONAL ANTICANCER DRUG DELIVERY CLINICAL EXAMPLES OF REGIONAL ANTINEOPLASTIC DRUG DELIVERY CONCLUSION REFERENCES TABLES 48. Drug Resistance and its Clinical Circumvention INTRODUCTION GENERAL MECHANISMS OF DRUG RESISTANCE RESISTANCE TO MULTIPLE DRUGS RESISTANCE FACTORS UNIQUE TO TUMOR CELLS IN VIVO: HOST-TUMOR-DRUG INTERACTIONS POTENTIAL CLINICAL APPLICATION OF STRATEGIES TO AVERT OR OVERCOME DRUG RESISTANCE CONCLUSION AND FUTURE DIRECTIONS REFERENCES TABLES FIGURES Section 12 - CHEMOTHERAPEUTIC AGENTS 49. Folate Antogonists INTRODUCTION HISTORICAL OVERVIEW MECHANISM OF ACTION PHARMACOKINETICS OF MTX INADVERTENT DRUG INTERACTIONS WITH MTX CLINICAL APPLICATION ADVERSE EFFECTS RESISTANCE TO ANTIFOLATES STRATEGIES TO OVERCOME RESISTANCE TO MTX USING NEW (OR OLDER) ANTIFOLS REFERENCES TABLES FIGURES 50. Pyrimidine and Purine Antimetabolites INTRODUCTION PYRIMIDINE ANALOGS PURINE ANALOGS REFERENCES FIGURES 51. Alkylating Agents and Platinum Antitumor Compounds INTRODUCTION ALKYLATING AGENTS REFERENCES FIGURES 52. Anthracyclines and DNA INTRODUCTION TOPOISOMERASE BIOLOGY HOW DRUGS "POISON" TOPOISOMERASES CELLULAR RESPONSE TO TOPOISOMERASE-MEDIATED DNA DAMAGE MECHANISMS OF RESISTANCE TO TOPOISOMERASE TARGETING INTERCALATING DRUGS THAT TARGET TOPOISOMERASES NONINTERCALATING TOPOISOMERASE-TARGETING DRUGS REFERENCES TABLES FIGURES 53. Microtubule-Targeting Natural Products INTRODUCTION MICROTUBULES AS STRATEGIC TARGETS AGAINST CANCER THE VINCA ALKALOIDS THE TAXANES NOVEL COMPOUNDS TARGETING MICROTUBULES AND RELATED ORGANELLES REFERENCES TABLES FIGURES 54. Small-Molecule Inhibitors of Protein Kinases in the Treatment of Human Cancer INTRODUCTION STRATEGIES TO INHIBIT TYROSINE KINASES TYROSINE KINASE INHIBITORS: TARGETING CONSIDERATIONS KIT AS A THERAPEUTIC TARGET PDGF RECEPTORS AS THERAPEUTIC TARGETS ARG (ABELSON-RELATED GENE) AS A THERAPEUTIC TARGET TOXICITY OF TKIS CONSIDERATIONS IN CLINICAL TRIAL DESIGN FOR TYROSINE KINASE INHIBITORS REFERENCES TABLES FIGURES Section 13 - BIOTHERAPEUTICS 55. Asparaginase INTRODUCTION MECHANISM OF ACTION, CHEMISTRY, AND IN VITRO ACTIVITY CONCLUSIONS REFERENCES TABLES FIGURES 56. Interferons INTRODUCTION MOLECULES: THEIR INDUCTION, RECEPTORS, AND GENE REGULATION MECHANISMS OF ANTITUMOR ACTION ANGIOGENESIS INHIBITION ANTITUMOR EFFECTS IN HUMANS PERSPECTIVE REFERENCES TABLES FIGURES 57. Cytokines: Biology and Applications in Cancer Medicine INTRODUCTION INTERLEUKIN-2 INTERLEUKIN-12 TUMOR NECROSIS FACTOR-a INTERLEUKIN-1 INTERLEUKIN-6 INTERLEUKIN-4 COLONY-STIMULATING FACTORS CYTOKINES CONSIDERED FOR CLINICAL APPLICATION OR IN EARLY TRIALS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES 58. Hematopoietic Growth Factors INTRODUCTION HEMATOPOIESIS AND THE ROLE OF GROWTH FACTORS ERYTHROPOIETIN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GRANULOCYTE COLONY- STIMULATING FACTOR MACROPHAGE COLONY- STIMULATING FACTOR STEM CELL FACTOR THROMBOPOIETIN INTERLEUKIN-1 INTERLEUKIN-2 INTERLEUKIN-3 INTERLEUKIN-4 AND INTERLEUKIN-13 INTERLEUKIN-5 INTERLEUKIN 6 INTERLEUKIN-7 INTERLEUKIN-8 INTERLEUKIN-9 INTERLEUKIN-11 INTERLEUKIN-15 INTERLEUKIN-16 INTERLEUKIN-17 INTERLEUKIN-18 OTHER HEMATOPOIETIC GROWTH FACTORS USE OF HEMATOPOIETIC GROWTH FACTORS AFTER CHEMOTHERAPY HEMATOPOIETIC GROWTH FACTORS IN THE TRANSPLANTATION SETTING THROMBOPOIETIC AGENTS IN THE CLINIC: AN OVERVIEW HEMATOPOIETIC GROWTH FACTORS IN BONE MARROW FAILURE STATES FUTURE PERSPECTIVES REFERENCES TABLES FIGURES 59. Monoclonal Serotherapy INTRODUCTION THERAPY WITH UNMODIFIED MONOCLONAL ANTIBODIES BARRIERS TO SUCCESSFUL SEROTHERAPY ELIMINATION OF MALIGNANT CELLS FROM BONE MARROW EX VIVO THERAPY WITH DRUG-MONOCLONAL ANTIBODY CONJUGATES RADIOIMMUNOTHERAPY OF CANCER TARGETED TOXINS CONCLUSIONS REFERENCES TABLES FIGURES 60. Vaccines and Immunostimulants INTRODUCTION TARGETS FOR VACCINE THERAPY ISSUES IN CANCER VACCINE DEVELOPMENT nbsp; PROBLEM AREAS IN IMMUNOTHERAPY TYPES OF VACCINES DIVERSIFIED PRIME AND BOOST IMMUNIZATION STRATEGIES IMMUNOSTIMULANTS/CYTOKINES T-CELL COSTIMULATION ADOPTIVE TRANSFER VACCINE CLINICAL TRIALS CONCLUSION ACKNOWLEDGMENTS REFERENCES TABLES Section 14 - ENDOCRINE THERAPY 61. Hypothalamic and Other Peptide Hormones INTRODUCTION ANALOGS OF PEPTIDE HORMONES AGONISTS OF LHRH LHRH ANTAGONISTS MODE OF ACTION OF LHRH ANALOGS SOMATOSTATIN ANALOGS ANTAGONISTS OF BOMBESIN AND GASTRIN-RELEASING PEPTIDE ANTAGONISTS OF GROWTH HORMONE-RELEASING HORMONE TREATMENT OF VARIOUS TUMORS WITH PEPTIDE ANALOGS TUMORS PRODUCING HYPOTHALAMIC HORMONES REFERENCES TABLES FIGURES 62. Corticosteroids INTRODUCTION HORMONES OF THE ADRENAL CORTEX CONTROL OF CORTICOSTEROID SECRETION PHARMACOKINETICS OF CORTICOSTEROIDS STEROID SYNTHESIS INHIBITORS PHARMACEUTICAL DERIVATIVES PHYSIOLOGIC AND PHARMACOLOGIC EFFECTS OF CORTICOSTEROIDS CORTICOSTEROIDS IN THE TREATMENT OF NEOPLASMS REFERENCES TABLES FIGURES 63. Estrogens and Antiestrogens INTRODUCTION TAMOXIFEN NEW AGENTS CONCLUSION REFERENCES TABLES FIGURES 64. Aromatase Inhibitors INTRODUCTION BIOLOGY OF AROMATASE HISTORICAL DEVELOPMENT OF AROMATASE INHIBITORS DEVELOPMENT OF IMPROVED AROMATASE INHIBITORS CLASSIFICATION SELECTION OF PATIENTS FOR AROMATASE INHIBITION THERAPY FUTURE PERSPECTIVES IN THE CLINICAL DEVELOPMENT OF AROMATASE INHIBITORS SUMMARY REFERENCES TABLES FIGURES 65. Progestins INTRODUCTION PHYSIOLOGY PHARMACOLOGY CLINICAL OBSERVATIONS ON PROGESTIN RECEPTOR AND TARGET TISSUE RESPONSES TO PROGESTINS CONCLUSION REFERENCES 66. Androgen Deprivation Strategies in the Treatment of Advanced Prostate Cancer INTRODUCTION 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 ANDROGEN DEPRIVATION STRATEGIES FOR THE TREATMENT OF RECURRENT AND METASTATIC PROSTATE CANCER ALTERNATIVE STRATEGIES FOR ANDROGEN DEPRIVATION CONCLUSION REFERENCES TABLES FIGURES Section 15 - GENE THERAPY 67. Cancer Gene Therapy INTRODUCTION GENE DELIVERY SYSTEMS THERAPEUTIC GENES SELECTIVE GENE EXPRESSION VIRAL ONCOLYSIS REFERENCES TABLES FIGURES Section 16 - BONE MARROW TRANSPLANTATION 68. Autologous Bone Marrow and Stem Cell Transplantation INTRODUCTION RATIONALE AND REQUIREMENTS FOR AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION PRINCIPLES DOSE INTENSITY COMBINATION CHEMOTHERAPY VOLUME OF DISEASE PROCEDURE SPECIFIC DISEASES AUTOIMMUNE DISEASES TOXICITIES IMMUNE FUNCTION POSTTRANSPLANT ORGAN TOXICITY FUTURE DIRECTIONS REFERENCES TABLES FIGURES 69. Hematopoietic Cellular Transplantation INTRODUCTION 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 INDICATIONS FOR HEMATOPOIETIC TRANSPLANTATION FUTURE DIRECTIONS REFERENCES TABLES FIGURES Section 17 - PSYCHO-ONCOLOGY 70. Psycho-Oncology INTRODUCTION HISTORICAL PERSPECTIVE HEARING THE DIAGNOSIS FACTORS IN ADAPTATION TO CANCER PSYCHOSOCIAL PROBLEMS GUIDELINES FOR RECOGNITION OF PSYCHOSOCIAL DISTRESS PSYCHIATRIC DISORDERS SUMMARY REFERENCES TABLES FIGURES Section 18 - ONCOLOGY NURSING 71. Principles of Oncology Nursing INTRODUCTION ONCOLOGY NURSING AS A SPECIALTY ROLE OF THE ONCOLOGY NURSE SURVIVORSHIP ADVANCED PRACTICE IN ONCOLOGY NURSING NURSING SHORTAGE SUMMARY REFERENCES TABLES FIGURES Section 19 - CANCER REHABILITATION MEDICINE 72. Principles of Cancer Rehabilitation Medicine INTRODUCTION APPLICATION OF REHABILITATION CONCEPTS THE CANCER REHABILITATION AND ADAPTATION TEAM FUNCTIONAL ASSESSMENT THE REHABILITATION PROCESS CANCER OF THE BRAIN CANCER OF THE SPINE CANCER OF THE HEAD AND NECK CANCER OF THE LUNG CANCER OF THE BREAST CANCER OF THE GASTROINTESTINAL TRACT CANCER OF THE GENITOURINARY SYSTEM CANCER OF THE LIMBS CONCLUSION REFERENCES TABLES FIGURES Section 20 - MULTIDISCIPLINARY MANAGEMENT 73. Principles of Multidisciplinary Management INTRODUCTION 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 74. Cancer and Pregnancy INTRODUCTION CANCER AND PREGNANCY EPIDEMIOLOGY DIAGNOSIS AND STAGING CANCER TREATMENT DURING PREGNANCY SPECIFIC CANCERS OUTCOME OF CHILDREN EXPOSED TO CANCER THERAPY IN UTERO CONCLUSION REFERENCES TABLES 75. Cancer and Aging INTRODUCTION 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 CONCLUSIONS REFERENCES TABLES FIGURES 76. Complementary and Alternative Cancer Therapies INTRODUCTION THE EVOLUTION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE TERMINOLOGY AND DEFINITIONS IMPACT ON THE HEALTHCARE SYSTEM CAM USE AND USERS MAINSTREAM ACCEPTANCE OF CAM CAM THERAPIES AND PRACTITIONERS CAM PRACTITIONERS AND PRACTICES CAM RESEARCH ISSUES REFERENCES TABLES Section 21 - PAIN AND PALLIATION 77. Palliative Care INTRODUCTION THE ROLE OF THE ONCOLOGIST SUFFERING IN THE PATIENT, FAMILY, AND PHYSICIAN GUIDELINES IN THE CARE OF THE DYING PATIENT A LEGAL MANDATE FOR PALLIATIVE CARE CONCLUSION: THE NEED FOR EDUCATION AND TRAINING IN END-OF-LIFE CARE REFERENCES TABLES 78. Management of Cancer Pain INTRODUCTION SCOPE OF THE PROBLEM BARRIERS TO CANCER PAIN MANAGEMENT MECHANISMS OF CANCER PAIN TYPES OF PAIN STRATEGY FOR ASSESSMENT AND TREATMENT THERAPEUTIC APPROACHES TO CANCER PAIN PSYCHOLOGICAL AND BEHAVIORAL APPROACHES ANESTHETIC APPROACHES NEUROSURGICAL APPROACHES SEDATION IN THE IMMINENTLY DYING DEFINING THE CANCER PAIN RESEARCH AGENDA REFERENCES TABLES FIGURES Section 22 - SOCIETAL ONCOLOGY 79. Ethics in Oncology INTRODUCTION INFORMED CONSENT HUMAN SUBJECTS RESEARCH TERMINATING MEDICAL CARE ASSISTED SUICIDE AND EUTHANASIA FINANCIAL INCENTIVES CONFIDENTIALITY ETHICAL ISSUES IN CANCER GENETICS REFERENCES TABLES FIGURES 80. Cancer and the Law INTRODUCTION ELEMENTS OF LIABILITY PREVENTING LEGAL COMPLICATIONS 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 81. The Government and Cancer Medicine INTRODUCTION CANCER: A MAJOR NATIONAL HEALTHCARE PRIORITY LEGISLATIVE HISTORY OF THE NATIONAL CANCER PROGRAM FEDERAL SUPPORT FOR THE NATIONAL CANCER PROGRAM RETURN ON INVESTMENT FROM FEDERAL FUNDS PUBLIC ATTITUDES CONCERNING CANCER THE CANCER ADVOCACY MOVEMENT FEDERAL POLICIES AND CANCER RESEARCH THE FUTURE REFERENCES TABLES FIGURES 82. Clinical Oncology in a Changing Healthcare Environment INTRODUCTION 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 DEMANDS OF PATIENTS FACING TERMINAL ILLNESSES CURRENT STRATEGIES FOR THE DELIVERY OF CANCER CARE FUTURE DIRECTIONS IN HEALTHCARE REFORM REFERENCES Part VI - Cancer Management Section 23 - CENTRAL NERVOUS SYSTEM 83. Primary Neoplasms of the Central Nervous System INTRODUCTION EPIDEMIOLOGY RISK FACTORS MOLECULAR GENETICS FAMILIAL TUMORS SYNDROMES OF THE CENTRAL NERVOUS SYSTEM HISTOPATHOLOGY OF NEURO-EPITHELIAL CENTRAL NERVOUS SYSTEM TUMORS CLINICAL PRESENTATION DIAGNOSTIC NEUROIMAGING SURGICAL DIAGNOSIS AND RESECTION CORTICAL MAPPING AND INTERACTIVE IMAGE-GUIDED RESECTIONS POSTOPERATIVE IMAGING CLINICAL TRIALS GLIOBLASTOMA MULTIFORME AND ANAPLASTIC ASTROCYTOMA nbsp; ANAPLASTIC OLIGODENDROGLIOMA LOW-GRADE GLIOMAS EPENDYMOMA SPINAL CORD TUMORS ADULT MEDULLOBLASTOMAS OTHER PRIMARY TUMORS OF THE CENTRAL NERVOUS SYSTEM FUTURE DIRECTIONS ACKNOWLEDGMENTS REFERENCES TABLES FIGURES 84. Brain Metastases INTRODUCTION PATHOPHYSIOLOGY OF THE METASTATIC PROCESS TREATMENT REFERENCES TABLES FIGURES Section 24 - THE EYE 85. Neoplasms of the Eye INTRODUCTION PEDIATRIC OPHTHALMIC ONCOLOGY: OCULAR DISEASES PEDIATRIC OPHTHALMIC ONCOLOGY: ORBITAL DISEASES ADULT OPHTHALMIC ONCOLOGY: OCULAR DISEASES ADULT OPHTHALMIC ONCOLOGY: ORBITAL DISEASES ADULT OPHTHALMIC ONCOLOGY: LID DISEASE OPHTHALMIC COMPLICATIONS OF RADIATION AND CHEMOTHERAPY REFERENCES TABLES FIGURES Section 25 - ENDOCRINE GLANDS 86. Neoplasms of the Endocrine Glands: Pituitary Neoplasms INTRODUCTION PRL-SECRETING PITUITARY ADENMAS GH-SECRETING PITUITARY ADENOMAS ACTH-SECRETING ADENOMAS GONADOTROPIN-SECRETING AND NONSECRETING PITUITARY ADENOMAS TSH-SECRETING PITUITARY ADENOMAS REFERENCES FIGURES 87. Neoplasms of the Thyroid INTRODUCTION DIAGNOSTIC EVALUATION OF THE SOLITARY THYROID NODULE DIFFERENTIATED THYROID CARCINOMA MEDULLARY THYROID CANCER ANAPLASTIC THYROID CARCINOMA REFERENCES TABLES FIGURES 88. Neoplasms of the Adrenal Cortex INTRODUCTION PATHOGENESIS DIAGNOSIS DIFFERENTIAL DIAGNOSIS IMAGING CHARACTERIZATION STAGING PATHOLOGIC DIAGNOSIS CARCINOMA MANAGEMENT LONG-TERM TREATMENT OUTCOME ADRENAL FUNCTION INHIBITORS IN TREATMENT FUTURE PROSPECTS REFERENCES TABLES FIGURES 89. Neoplasms of the Diffuse Endocrine System INTRODUCTION ENDOCRINE NEOPLASMS OF THE GASTROENTEROPANCREATIC (GEP) SYSTEM PARATHYROID CARCINOMAS, PHEOCHROMOCYTOMAS, AND MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES MEN 2A, 2B, AND NON-MEN FAMILIAL MEDULLARY THYROID CARCINOMA REFERENCES TABLES FIGURES Section 26 - HEAD AND NECK 90. Neoplasms of the Head and Neck INTRODUCTION EPIDEMIOLOGY ANATOMY PATHOLOGIC ASSESSMENT DIAGNOSIS AND STAGING TREATMENT REFERENCES TABLES FIGURES 91. Odontogenic Tumors INTRODUCTION ECTODERMAL TUMORS ODONTOGENIC TUMORS DERIVED FROM MESODERM TUMORS ARISING FROM THE PERIODONTAL MEMBRANE MIXED ECTODERMAL-MESODERMAL ODONTOGENIC TUMORS AMELOBLASTIC ODONTOMA (ODONTOAMELOBLASTOMA) MALIGNANT ODONTOGENIC TUMORS REFERENCES TABLES FIGURES Section 27 - THE THORAX 92. Cancer of the Lung INTRODUCTION HISTORICAL NOTE FACTORS ASSOCIATED WITH THE DEVELOPMENT OF LUNG CANCER MOLECULAR PATHOGENESIS NATURAL HISTORY PERFORMANCE STATUS THERAPY FOR NSCLC THERAPY FOR SCLC CONCLUSION AND FUTURE PROSPECTS REFERENCES TABLES FIGURES 93. Malignant Mesothelioma INTRODUCTION HISTORICAL PERSPECTIVE INCIDENCE AND EPIDEMIOLOGY ETIOLOGY OTHER ETIOLOGIC FACTORS PATHOLOGY CLINICAL FEATURES PROGNOSTIC FACTORS OTHER TYPES OF MALIGNANT MESOTHELIOMAS BENIGN MESOTHELIOMAS DIFFERENTIAL DIAGNOSIS TREATMENT PROSPECTUS AND PREVENTION REFERENCES TABLES FIGURES 94. Thymomas and Thymic Tumors INTRODUCTION EPIDEMIOLOGY AND ETIOLOGY ANATOMIC PATHOGENESIS CLINICAL FEATURES ASSOCIATED PARANEOPLASTIC SYNDROMES DIAGNOSIS DIFFERENTIAL DIAGNOSIS STAGING THERAPY REFERENCES TABLES FIGURES 95. Tumors of the Heart and Great Vessels INTRODUCTION CARDIAC TUMORS TUMORS OF THE GREAT VESSELS REFERENCES TABLES 96. Primary Germ Cell Tumors of the Thorax INTRODUCTION BENIGN TERATOMAS OF THE MEDIASTINUM MALIGNANT GERM CELL TUMORS POORLY DIFFERENTIATED CARCINOMA OF THE MEDIASTINUM REFERENCES TABLES FIGURES 97. Metastatic Tumors in the Thorax INTRODUCTION MOLECULAR AND GENETIC BASIS FOR PULMONARY METASTASES DIAGNOSIS AND IMAGING NONSURGICAL TREATMENT OF PULMONARY METASTASES SURGICAL TREATMENT OF PULMONARY METASTASES PEDIATRIC TUMORS SUMMARY REFERENCES TABLES FIGURES Section 28 - GASTROINTESTINAL TRACT 98. Neoplasms of the Esophagus INTRODUCTION ANATOMY AND HISTOLOGY ETIOLOGY EPIDEMIOLOGY PRESENTATION TREATMENT OVERVIEW DIAGNOSIS PRETREATMENT ASSESSMENT STAGING EVALUATION THERAPY SINGLE-AGENT CHEMOTHERAPY PALLIATIVE THERAPY OF ESOPHAGEAL OBSTRUCTION REFERENCES TABLES FIGURES 99. Gastric Cancer INTRODUCTION EPIDEMIOLOGY ETIOLOGY PROXIMAL GASTRIC CANCER HISTOLOGY CLINICAL MANIFESTATIONS PATTERN OF SPREAD MOLECULAR BIOLOGY OF GASTRIC CANCER (TABLE 99-3) PATHOLOGIC AND CLINICAL STAGING THERAPY OF LOCOREGIONAL DISEASE CHEMORADIOTHERAPY FOR GASTRIC CANCER ADJUVANT THERAPY PREOPERATIVE CHEMOTHERAPY PREOPERATIVE CHEMORADIOTHERAPY PALLIATIVE THERAPY FOR ADVANCED DISEASE SYMPTOM MANAGEMENT OBSTRUCTION/DYSPHAGIA/ EARLY SATIETY NUTRITION CONCLUSIONS REFERENCES TABLES FIGURES 100. Primary Neoplasms of the Liver INTRODUCTION EPIDEMIOLOGY RISK FACTORS MOLECULAR PATHOGENESIS PREVENTION CLINICAL PRESENTATION PATHOLOGIC DIAGNOSIS STAGING AND PROGNOSIS IMAGING MODALITIES MANAGEMENT (FIGURE 100-3) OTHER PRIMARY HEPATIC NEOPLASMS REFERENCES TABLES FIGURES 101. Treatment of Liver Metastases INTRODUCTION IMAGING TECHNIQUES LIVER RESECTION