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دانلود کتاب Abeloff's clinical oncology
دانلود کتاب انکولوژی بالینی آبلف
مشخصات کتاب
Abeloff's clinical oncology
ویرایش: [6 ed.] نویسندگان: Martin D. Abeloff (editor), James O. Armitage (editor), James H Doroshow (editor), John E Niederhuber (editor), Joel E Tepper (editor), Michael B Kastan (editor) سری: ISBN (شابک) : 9780323476744, 0323568157 ناشر: Elsevier Inc. سال نشر: 2020 تعداد صفحات: [2648] زبان: English فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) حجم فایل: 134 Mb
قیمت کتاب (تومان) : 51,000
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توضیحاتی در مورد کتاب انکولوژی بالینی آبلف
انکولوژی بالینی Abeloff، ویرایش ششم که به راحتی قابل دسترسی و تمرکز بالینی است، پیشرفت‌های اخیر در درک ما از پاتوفیزیولوژی سرطان، علل سلولی و مولکولی شروع و پیشرفت سرطان، درمان‌های جدید و نوظهور، آزمایش‌های فعلی و موارد دیگر را پوشش می‌دهد. این کتاب که توسط یک تیم بین‌المللی از متخصصان برجسته سرطان نوشته شده است، پوششی واضح و عملی از همه چیز از علوم پایه گرفته تا همکاری چند رشته‌ای در تشخیص، مرحله‌بندی، درمان و پیگیری ارائه می‌دهد. شامل فصول جدید در مورد متابولیسم سرطان و طرح های کارآزمایی بالینی در انکولوژی و یک فصل مستقل در مورد سبک زندگی و پیشگیری از سرطان است. دارای به‌روزرسانی‌های گسترده از جمله آخرین دستورالعمل‌های عمل بالینی، الگوریتم‌های تصمیم‌گیری، و مفاهیم کارآزمایی بالینی، و همچنین محتوای جدید در مورد پزشکی دقیق، ژنتیک، و تصویربرداری PET/CT. شامل پروتکل‌های تشخیصی و درمانی اصلاح‌شده برای مدیریت پزشکی، ملاحظات جراحی، و درمان‌های انکولوژی پرتویی، که بر رویکرد چندتخصصی و یکپارچه برای مراقبت تاکید دارد. به شما کمک می کند اطلاعات را با نمایه سازی به روز مرتبط با توصیه های مدیریت، خلاصه واقعیت های متمرکز، نکات کلیدی به روز شده در ابتدای هر فصل برای مرجع سریع و بررسی هیئت مدیره، و الگوریتم هایی برای ارزیابی بیمار، تشخیص و گزینه های درمانی پیدا کنید. پوشش مراقبت از بیمار بیشتر در فصل های بیماری، به علاوه اطلاعات جدید در مورد سرطان به عنوان یک بیماری مزمن و نجات از سرطان را ارائه می دهد. در مورد موضوعات کلیدی امروزی مانند ایمونوآنکولوژی، تصویربرداری عملکردی، پزشکی دقیق، کاربرد ژنتیک در تشخیص پاتولوژیک و طبقه بندی فرعی تومورها و همچنین ارتباط بیماری های عفونی مزمن مانند HIV و سرطان بحث می کند. نسخه کتاب الکترونیکی پیشرفته همراه با خرید. کتاب الکترونیکی پیشرفته شما به شما امکان می دهد به تمام متن ها، شکل ها و مراجع کتاب در دستگاه های مختلف دسترسی داشته باشید.
توضیحاتی درمورد کتاب به خارجی
Easily accessible and clinically focused, Abeloff's Clinical Oncology, 6th Edition, covers recent advances in our understanding of the pathophysiology of cancer, cellular and molecular causes of cancer initiation and progression, new and emerging therapies, current trials, and much more. Masterfully authored by an international team of leading cancer experts, it offers clear, practical coverage of everything from basic science to multidisciplinary collaboration on diagnosis, staging, treatment and follow up. Includes new chapters on Cancer Metabolism and Clinical Trial Designs in Oncology and a standalone chapter on lifestyles and cancer prevention. Features extensive updates including the latest clinical practice guidelines, decision-making algorithms, and clinical trial implications, as well as new content on precision medicine, genetics, and PET/CT imaging. Includes revised diagnostic and treatment protocols for medical management, surgical considerations, and radiation oncology therapies, stressing a multispecialty, integrated approach to care. Helps you find information quickly with updated indexing related to management recommendations, focused fact summaries, updated key points at the beginning of each chapter ideal for quick reference and board review, and algorithms for patient evaluation, diagnosis, and treatment options. Offers more patient care coverage in disease chapters, plus new information on cancer as a chronic illness and cancer survivorship. Discusses today's key topics such as immuno-oncology, functional imaging, precision medicine, the application of genetics in pathologic diagnosis and sub-categorization of tumors as well as the association of chronic infectious diseases such as HIV and cancer. Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.
فهرست مطالب
Front Cover Inside Front Cover Abeloff\'s Clinical Oncology Copyright Page Dedication Memoriam Contributors Preface Acknowledgments Table Of Contents I Science and Clinical Oncology A Biology and Cancer 1 Molecular Tools in Cancer Research Summary of Key Points Our Unstable Heredity Detecting Cancer Mutations Generating Diversity With Alternate Splicing Genomics of Cancer Building Gene Libraries Losing Control of the Genome Epigenetics and Cancer Profiling Tumors Cancer Proteome Modeling Cancer In Vivo Transgenic Models of Cancer Conditional Control of Oncogene Activation Models of Recessive Gene Mutations in Cancer Exploiting Mouse Diversity for Cancer Research Future View Suggested Readings 2 Intracellular Signaling Summary of Key Points Receptor Tyrosine Kinase Signaling Epidermal Growth Factor Receptor Signaling Insulin, Insulin-Like Growth Factor-1 Receptor Signaling, ALK, and ROS1 Platelet-Derived Growth Factor Receptor, KIT, and FLT-3 Signaling Fibroblast Growth Factor Receptor Signaling RET Signaling Vascular Endothelial Growth Factor Signaling Hepatocyte Growth Factor Receptor Signaling Tropomyosin Receptor Kinases/Neurotrophic Tyrosine Kinase G Protein–Coupled Receptor Signaling Cytokine Receptor Signaling Serine/Threonine Receptor Signaling Notch Receptor Signaling Nuclear Hormone Receptor Signaling Integrin Receptor Signaling Non–Receptor Tyrosine Kinase Signaling SRC Signaling ABL Signaling Ras/MAP Kinase Pathway Signaling PI3 Kinase/Akt/mTOR Pathway Signaling Translational Implications Key References References Self-Assessment Review Questions Answers 3 Cellular Microenvironment and Metastases Summary of Key Points Tumor Microenvironment and Metastasis Cancer Stem Cells Angiogenic Vascular Cells Endothelial Cells Pericytes Immune Cells Macrophages Neutrophils Platelets Fibroblasts and Mesenchymal Stem Cells Extracellular Vesicles Hypoxia Patterns of Metastasis Seed and Soil Hypothesis Premetastatic Niche Organ Specificity Metastases to the Bone Metastases to the Brain Metastases to the Lung Metastases to the Liver Clinical Relevance and Applications Conclusion Key References References 4 Control of the Cell Cycle Summary of Key Points Cell Division Cycle Overview of the Cell Cycle Machinery Cyclin-Dependent Kinases and Their Regulators Retinoblastoma Proteins and E2F Transcription Factors Ubiquitin-Dependent Protein Degradation Mitotic Spindle and Mitotic Kinases and Kinesins Cell Cycle Phosphatases Entry Into the Cell Cycle DNA Replication Mitosis Mitotic Entry Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis Cell Cycle Checkpoints G1/S Checkpoint Intra–S Phase Checkpoint G2 Checkpoint Spindle Assembly Checkpoint Cell Cycle Deregulation in Human Cancers Unscheduled Cell Cycle Entry in Cancer Mutations in p53 and Checkpoint Regulators Aneuploidy and Chromosomal Instability Therapeutic Manipulation of Cell Cycle Controls Targeting Cyclin-Dependent Kinase Activity Targeting DNA Damage Response Proteins Targeting the Mitotic Spindle Targeting Mitotic Entry and Exit Targeting the Spindle Assembly Checkpoint and Aneuploidy Summary Key References Additional Resources References 5 Pathophysiology of Cancer Cell Death Summary of Key Points Fundamental Science: Mechanisms of Cell Death Apoptosis Necrosis Necroptosis Mitochondrial Permeability Transition–Driven Regulated Necrosis Other Forms of Regulated Cell Death Ferroptosis Pyroptosis Parthanatos Autophagy Fundamental Science: Cell Death and Cancer Oncogenes and Cell Death Regulation Oncosuppressors and Cell Death Regulation Clinical Relevance and Applications What the Future Holds Key References References Self-Assessment Review Questions Answers 6 Cancer Immunology Summary of Key Points Overview The Antigenic Profile That Distinguishes Tumors From Normal Tissues Immune Surveillance Hypothesis of Cancer Immune Hallmarks of Cancer: Avoiding Immune Destruction and Tumor-Promoting Inflammation Avoiding Immune Destruction Tumor-Promoting Inflammation in the Tumor Microenvironment Regulatory T Cells and Cancer Immature Myeloid Cells and Tumor-Associated Macrophages Immature Dendritic Cells Immune Inhibitory Molecules Expressed in the Tumor Microenvironment Transforming Growth Factor–β: A Major Inhibitory Cytokine in the Tumor Microenvironment Coinhibitory Ligands and Receptors That Downmodulate Tumor Immunity CTLA-4 Checkpoint: A Global Regulator of T-Cell Activation PD-1 Checkpoint: A Pathway That Functions Within the Tumor Microenvironment Additional Checkpoints Participate in Tumor Immune Resistance and Tolerance Implications for Cancer Immunotherapy Checkpoint Blockade Immunotherapy Using Adoptive T-Cell Strategies Tumor-Infiltrating Lymphocytes Genetically Engineered Adoptive T-Cell Strategies Genetically Modified T-Cell Receptors for Adoptive Cellular Therapy Chimeric Antigen Receptors for Adoptive Cellular Therapy Clinical Translation of Chimeric Antigen Receptor Therapy Hematologic malignancies Solid tumors Cancer Vaccines Conclusions Key References References 7 Stem Cells, Cell Differentiation, and Cancer Summary of Key Points Properties of Normal Stem Cells Genetic Regulation of Self-Renewal Target Cells for Malignant Transformation Evidence for Cancer Stem Cells Clinical Implications of Cancer Stem Cells Future Implications of Cancer Stem Cells Acknowledgments Key References References Self-Assessment Review Questions Answers 8 Tumor Microenvironment Summary of Key Points Vascular Compartment New Vessel Formation Cellular Mechanisms Molecular Mechanisms Vascular Architecture Blood Flow and Microcirculation Vascular Permeability Movement of Cells Across Vessel Walls Extravascular Compartment Composition and Origin Interstitial Transport Lymphangiogenesis and Lymphatic Transport Interstitial Hypertension Metabolic Microenvironment Hypoxia Low pH Molecular, Cellular, and Therapeutic Consequences Clinical Relevance of Approaches to Alleviate Hypoxia Vascular Normalization Through Antiangiogenic Therapy Biomarkers of Response to Antiangiogenic Therapy Toxicity of Antiangiogenic Therapy Solid Stress Alleviation Through Stromal Reprogramming Perspective Conclusion Acknowledgments Key References References Self-Assessment Questions Answers 9 Cancer Metabolism Summary of Key Points Fundamental Science Warburg Effect Amino Acid Metabolism Mitochondrial Metabolism Lipid Metabolism Metabolism and Epigenetics Nutrient Heterogeneity and Tumor Microenvironment Obesity and Cancer Clinical Relevance and Applications Antimetabolite Chemotherapy Antifolates Nucleotide Synthesis Inhibitors Current Metabolic Drug Targets IDH1/2 Glutaminase Inhibitors Fatty Acid Synthase Inhibitors Indolamine 2,3-Dioxygenase Inhibitors Ornithine Decarboxylase Inhibitors Repurposing Common Metabolic Agents Metformin Statins Aspirin Vitamins C and D Diet and Exercise Metabolic Biomarkers and Diagnostics Fluorine-18 Fluorodeoxyglucose–Positron Emission Tomography Other Positron Emission Tomography Agents Conclusions and Future Outlook Key References References B Genesis of Cancer 10 Environmental Factors Summary of Key Points Current Concepts in Carcinogenesis Identification of Human Carcinogens Role of Environmental Agents in the Etiology of Human Cancer Exposure Biomarkers, Susceptibility Factors, and Prevention Evolving Models for Chemical Carcinogenesis History of Environmental Carcinogenesis and Support for the Role of Environmental Agents in the Etiology of Human Cancers Chemical Biology of Carcinogenesis Exposure Biomarkers and Assessing Human Exposure Carcin-Omics and the Exposome Approach to Environmental Carcinogenesis Epigenomic Exposure Profiling Transcriptomic Exposure Profiling Metabolomic Exposure Profiling Microbiome Chemicals Polycyclic Aromatic Hydrocarbons Aromatic Amines Benzene Aflatoxins Tobacco Chemicals Chemotherapeutic Agents Radiation Carcinogenesis Ultraviolet Radiation Ionizing Radiation Radon Metals Arsenic Nickel and Chromium Fibers Asbestos Dietary Factors in Human Carcinogenesis Genetic Polymorphisms and Human Susceptibility Public Health Approaches to Cancer Prevention and Interception Summary Key References References 11 DNA Damage Response Pathways and Cancer Summary of Key Points Types of DNA Damage Consequences of DNA Damage DNA Damage Response Pathways Types of DNA Repair and Their Contribution to Cancer Nucleotide Excision Repair Human Nucleotide Excision Repair–Deficient Syndromes and Cancer Base Excision Repair Mismatch Repair Human Mismatch Repair Deficiency and Cancer Double-Strand Break Repair Ataxia-Telangiectasia p53 Gene and Li-Fraumeni Syndrome BRCA1, BRCA2, and Breast-Ovarian Cancer Susceptibility Fanconi Anemia, Cancer, and Interstrand Cross-link Repair Conclusions and Future Directions Key References References Self-Assessment Review Questions Answers 12 Viruses and Human Cancer Summary of Key Points Epstein-Barr Virus Hepatitis B Virus Human Papillomaviruses Human T-Cell Leukemia Virus Type I Human Hepatitis C Virus Kaposi Sarcoma Herpesvirus Merkel Cell Polyomavirus Treatment and Prevention of Viral Tumors Hepatitis B Virus Vaccine Human Papillomavirus Vaccine Key References References 13 Genetic Factors Summary of Key Points Common Syndromes of Cancer Predisposition Breast and Ovarian Cancer Syndromes Clinical Features Genetics Other Genes Clinical Management Cowden Syndrome Clinical Features Genetics Risk Management Recommendations Common Colon Cancer Predisposition Syndromes Lynch Syndrome Clinical features Genetics Clinical management Polyposis Syndromes Familial adenomatous polyposis Clinical features. Genetics. Clinical management. Attenuated familial adenomatous polyposis Clinical features. Genetics. Clinical management. MUTYH-associated polyposis Clinical features. Genetics. Management. Other hereditary predisposition to colon cancer Hereditary Diffuse Gastric Cancer Clinical Features Genetics Clinical Management Pancreatic Adenocarcinoma Predisposition Syndromes Clinical Features Genetics Clinical Management Carney Complex Clinical Features Genetics Clinical Management Hereditary Paraganglioma-Pheochromocytoma Syndromes Clinical Features Genetics Clinical Management A Selection of Cancer Predisposition Syndromes With Targeted Therapies Multiple Endocrine Neoplasia Type 2 Clinical Features Genetics Clinical Management Gorlin Syndrome and Nevoid Basal Cell Carcinoma Syndrome Genetics Risk Management Recommendations Hereditary Leiomyomatosis Renal Cell Cancer Syndrome Clinical Features Genetics Clinical Management von Hippel-Lindau Disease Clinical Features Genetics Screening for von Hippel-Lindau Disease Systemic Therapy in von Hippel-Lindau Disease Birt-Hogg-Dubé Syndrome Clinical Features Genetics Risk Management Tuberous Sclerosis and Gastrointestinal Stromal Tumor BAP1 Inherited Cancer Susceptibility Tumor-Normal Sequencing Conclusion Acknowledgments Key References References 14 Genetic and Epigenetic Alterations in Cancer Summary of Key Points Recurrent Mutational Targets in Cancer Cancers Arise From the Accumulation of Multiple Genetic and Epigenetic Defects Clonal Selection and Evolution in Cancer Contribution of Gene Defects to the Signature Traits of Cancer Cells Alterations in Cancer Target Conserved Signaling Pathways and Networks Epigenetic Mechanisms of Proto-oncogene Activation and Tumor Suppressor Inactivation Mutations Affecting DNA Methylation Enzymes Mutations in Histones, Histone Modifiers, and Chromatin Remodelers Alterations in DNA cis-Regulatory Landscape in Cancer Noncoding RNAs in Cancer—microRNAs and Long Noncoding RNAs Genetic and Epigenetic Alterations and Genomic Integrity Role of Tissue and Context Differences in the Contributions of Gene Defects to Cancer Cell Phenotype Clinical Implications Key References References C Diagnosis of Cancer 15 Pathology, Biomarkers, and Molecular Diagnostics Summary of Key Points Early Detection of Cancer: Three Successes in Reducing Cancer Mortality Discussed as Early Detection Models Cervix and a Validated Biomarker Colon and Multistep Carcinogenesis With Hereditary Components Familial Adenomatous Polyposis Hereditary Nonpolyposis Colorectal Cancer MUTYH-Linked Polyposis Hamartomatous Polyposes Juvenile Polyposis Other Polyposes Biomarkers for Colon Cancer Screening Genetic tests Other screening biomarkers Lung Carcinogenesis and a Known Carcinogen Premalignant Lesions in the Lung Central airway premalignancy: squamous dysplasia Atypical adenomatous hyperplasia, adenocarcinoma in situ, and lepidic carcinoma Molecular Changes During Lung Carcinogenesis Tumor suppressor gene methylation Aneuploidy TP53 mutation High-throughput technologies Other Organ Sites Conclusion: Cells and Molecules in Early Detection Diagnosis and Classification of Solid Malignancies: Histology and Expanding Role of Molecular Diagnostics Algorithm for Cellular Molecular Testing Accessioning and Informatics Tissue Collection and Processing Resection Specimens Gross dissection. Specimen preservation. Biopsies Enriching for Tumor Cells Liquid Biopsy Treatment Targets and Molecular Analysis DNA: Next-Generation (Massively Parallel) Sequencing as a Biomarker Predicting Response to Treatment Definition Platforms Informatics pipeline Quality assurance Genetic alterations detected Interpretation and significance of next-generation sequencing results Assays for Large-Scale Gene and Chromosome Rearrangements Fluorescence in situ hybridization assays for chromosome rearrangement Molecular methods for genomic rearrangement Clinical Testing for Predictive Biomarkers by Immunohistochemistry Abnormal Expression of Target Genes ER, PR, and HER2 in breast cancer CDX2 expression in stage II colon carcinoma EGFR expression in lung carcinoma Aberrant Expression of Altered Genes ALK ROS1 and other markers Markers of Immune Response Mutational burden Mismatch repair deficiency and microsatellite instability PD-1 and PD-l1 expression detected with immunohistochemistry Tumor-associated lymphocytes Examples of Tumor- and Organ-Specific Mutational Profiles Gastrointestinal Stromal Tumors Colorectal Carcinoma KRAS as a prognostic marker in colorectal carcinoma KRAS as a predictor of treatment response in colorectal carcinoma. BRAF mutation and prognosis Other Mutations Lung Carcinoma—A Heterogeneous Tumor Single-Nucleotide Variants, Small Deletions and Insertions Epidermal growth factor receptor KRAS Large-Scale Rearrangements ALK Summary Melanoma: Targeted Treatment of an Aggressive Tumor BRAF KIT NRAS GNAQ/GNA11/BAP1 Central Nervous System: Classification by Molecular Diagnostics IDH1/IDH2 1p/19q codeletion Histone mutations ATRX TERT promoter BRAF C11orf95-RELA fusions Other mutations Regulatory Considerations Key References References 16 Imaging Summary of Key Points Tasks for Imaging General Considerations Performance of Imaging Tests Sensitivity Specificity Accuracy of Imaging Positive and Negative Predictive Values Receiver Operating Characteristic Curves Other Approaches to Assessing the Value of Imaging Screening Concepts and Challenges Screening Costs Size of Detectable Lesions Stage Migration Major Imaging Modalities Plain-Film Radiographs Mammography Computed Tomography Angiography Ultrasonography Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Nuclear Medicine and Positron Emission Tomography Optical Imaging Methods Radiation Dose and Imaging Anatomic Versus Functional Imaging Limitations of Anatomic Imaging of Cancer Molecular and Functional Alterations in Cancer Disease-Specific Imaging Recommendations Lung Cancer Evaluation of the Adrenal Breast Cancer Prostate Cancer (Table 16.3) Evaluation of the Prostate Colon Cancer Gynecologic Neoplasms Lymphoma Melanoma Bladder Carcinoma Head and Neck Cancer Pancreatic Carcinoma Liver Cancer Kidney Cancer Endocrine Tumors Brain Tumors Pediatric Tumors Esophageal and Gastric Cancer Sarcomas Gastrointestinal Stromal Tumors Treatment Response Assessment Defining Normal Organ Function for Cancer Therapy Guidance of Radiation Therapy Interventional Procedures Emerging Opportunities in Imaging Summary Key References References Self-Assessment Review Questions Answers D Clinical Trials 17 Biostatistics and Bioinformatics in Clinical Trials Summary of Key Points Biostatistics Applied to Cancer Research Clinical Trials Frequentist Approach Bayesian Approach Adaptive Designs of Clinical Trials Bioinformatics Challenges Pace of Technologic Change Breadth of Technologies Batch Effects and Experimental Design Multiple Testing and Overfitting Sequencing Best Practices Discovery Phase Test Validation Phase Evaluation of Clinical Utility Signatures Are Not Enough Clustering Is Not Prediction Precision Medicine Biomarker-Driven Adaptive Clinical Trials and Case Studies Case Studies Oncotype DX BATTLE Trial Conclusions Key References References 18 Clinical Trial Designs in Oncology Summary of Key Points Phase I Designs Combinations of Agents Late Dose-Limiting Toxicities Biologic End Points Phase II Designs Randomized Screening Designs Randomized Selection Designs Designs With Biomarkers Phase III Designs Randomization and Stratification Multiarm Trials Noninferiority Trials Nonrandomized Trial Designs Interim Monitoring Stopping for Superiority (Efficacy) in a Randomized Clinical Trial Stopping for Inefficacy (Futility) in a Randomized Clinical Trial Other Considerations for Efficacy and Inefficacy Monitoring Outcome-Adaptive Randomization Monitoring for Rare Serious Toxicities Phase II/III Designs End Points for Randomized Trials Overall Survival Progression-Free Survival Disease-Free Survival Tumor Response Rates Patient-Reported Outcomes Functional Outcomes Trial-Level Surrogate End Points Phase III Trial Designs With a Single Biomarker Prognostic and Predictive Biomarkers Enrichment Designs Biomarker-Stratified Designs Biomarker-Strategy Designs Designs With a Continuous Biomarker Designs With Multiple Biomarkers Biomarker-Directed Treatment Designs Nonbiomarker Directed Designs Conclusions Key References References 19 Structures Supporting Cancer Clinical Trials Summary of Key Points National Cancer Institute–Sponsored Clinical Trial Activities Cancer Trials Support Unit Central Institutional Review Board National Cancer Institute National Clinical Trials Network Other National Cancer Institute–Sponsored Structures Supporting Clinical Trials National Cancer Institute Community Oncology Research Program Phase I and II Early Therapeutic Clinical Trials Networks National Cancer Institute Drug Development Project Teams Biopharmaceutical Industry–Sponsored Cancer Clinical Trials Purpose and Nature of Industry-Sponsored Clinical Trials Particular Characteristics of Industry-Sponsored Trials Impact of Globalization on Pharmaceutical Development Models for the Conduct of Industry Clinical Trials Changing Nature of Oncology Trials: Impact on Infrastructure Expectations of Clinical Research Sites Quality Assurance, Monitoring, and Audits Educational and Training Tools and New Federal Guidelines Conclusion References 20 Oncology and Health Care Policy Summary of Key Points Background Research Health Care Insurance Cost of Care Health Information Technology Conclusion References E Prevention and Early Detection 21 Discovery and Characterization of Cancer Genetic Susceptibility Alleles Summary of Key Points Fundamental Science Genetic Variation in the Human Genome Principles of Linkage Mapping Challenges in Finding Cancer Susceptibility Genes Principles of Association Testing Study Design and Association Studies Association Studies in Cancer Genetic Architecture Underlying Cancer Susceptibility Unraveling the Cancer Biology of Cancer Susceptibility Alleles Clinical Implications of Cancer Susceptibility Alleles Next-Generation Sequencing Analysis Clinical Relevance and Applications Genetic Counseling and Testing What the Future Holds Key References References 22 Lifestyle and Cancer Prevention Summary of Key Points Rationale for Prevention Prevention Through Lifestyle Interventions Tobacco Alcohol The Role of Alcohol in Cancer Proposed Mechanisms Linking Alcohol With Cancer Evidence-Based Interventions for Cancer Prevention Related to Alcohol Use Obesity Role of Obesity in Cancer Proposed Mechanisms Linking Obesity With Cancer Physical Inactivity Role of Physical Inactivity in Cancer Proposed Mechanisms Linking Physical Activity With Reduced Cancer Risk Diet Dietary Components Linked With Increased Cancer Risk Red meat and processed meats High-salt foods and salt intake Proposed mechanisms of dietary components linked with increased cancer risk Dietary Components Linked With Decreased Cancer Risk Fruits and vegetables Vegetarian and vegan dietary pattern Mediterranean dietary pattern Individual micronutrients Proposed mechanisms of dietary components linked with decreased cancer risk Obesity, Physical Inactivity, and Dietary Recommendations and Resources for Cancer Prevention Ultraviolet Radiation The Role of Ultraviolet Radiation in Cancer Proposed Mechanism Linking Ultraviolet Radiation to Skin Cancer Evidence-Based Interventions for Cancer Prevention Related to Ultraviolet Radiation Exposure Family History Molecular Prevention Lung Cancer β-Carotene Alpha-Tocopherol, Beta-Carotene Cancer Trial (ATBC) Beta-Carotene and Retinol Efficacy Trial (CARET) Selenium Nutritional Prevention Cancer Trial (NPC) Selenium and Vitamin E Cancer Prevention Trial (SELECT) Selenium Supplementation in Patients With Resected Stage I Non–Small Cell Lung Cancer: ECOG 5597 Budesonide Nonsteroidal Antiinflammatory Drugs Sulindac. Iloprost Serine/Threonine Kinase Inhibitors myo-Inositol Retinoids Lung Intergroup Trial (LIT) 13-cis–retinoic acid with or without α-tocopherol Other Agents Head and Neck Cancers Retinoids Retinoid Head and Neck Second Primary (HNSP) trial Eastern Cooperative Oncology Group study Peroxisome Proliferator-Activated Receptor Agonists Celecoxib Erlotinib Bowman-Birk Inhibitor Concentrate Other Agents Esophageal Cancers Esophageal Squamous Cell Carcinoma Esophageal Adenocarcinoma Nonsteroidal Antiinflammatory Drugs Colorectal Cancer Nonsteroidal Antiinflammatory Drugs Selenium Nutritional prevention of cancer trial (NPCT). Selenium and vitamin E cancer prevention trial (SELECT). Women’s Health Initiative. Selenium and Celecoxib (Sel/Cel) Trial. Aspirin Cyclooxygenase-2 inhibitors Calcium Vitamin D/Calcium Polyp Prevention Study Hormone Replacement Therapy Other Drugs Curcumin Eflornithine Eicosapentanoic Acid Mesalamine Metformin Vaccines Gastric Cancer Helicobacter pylori Nonsteroidal Antiinflammatory Drugs Cyclooxygenase-2 Inhibitors Hepatocellular Cancer Hepatitis B Virus and Hepatitis C Virus Vaccine Other Strategies Capecitabine Atorvastatin Interferon Lamivudine Glycyrrhizin Breast Cancer Selective Estrogen Receptor Modulators Aromatase Inhibitors Prevention of Estrogen Receptor–Negative Breast Cancer Other Strategies to Prevent Breast Cancer Cervical Cancer Human Papillomavirus Vaccine bHPV (Cervarix) qHPV (Gardasil) 9vHPV (Gardasil 9) Prostate Cancer 5α-Reductase Inhibitors Prostate Cancer Prevention Trial (PCPT) Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial Selenium and Vitamin E Aspirin Other Agents Bladder Cancer Bacillus Calmette-Guérin Valrubicin Chemotherapy Celecoxib Metformin Toll-Like Receptor Agonist Other Drugs Skin Cancer Nonmelanoma Skin Cancers Retinoids Nonsteroidal antiinflammatory drugs Cyclooxygenase-2 inhibitors d,l-α-Difluoromethylornithine Vismodegib Statins Vitamins and minerals Melanoma Nonsteroidal antiinflammatory drugs Statins Vitamins, minerals, and dietary factors Other agents Key References References 23 Screening and Early Detection Summary of Key Points Risk Assessment Screening and Early Detection Breast Cancer Risk Modeling and Assessment Screening Breast Awareness Clinical Breast Examination Screening Mammography Colorectal Cancer Risk Modeling and Assessment Screening Cervical Cancer Cervical Cancer Screening Current Cervical Cancer Screening: Cytologic Assessment With or Without Human Papillomavirus Testing Emerging Tests for Cervical Cancer Screening: Primary Human Papillomavirus Screening Lung Cancer Risk Factors Risk Modeling Screening Prostate Cancer Risk Modeling and Assessment Screening Pancreatic Cancer Risk Factors and Inherited Syndromes Screening Liver Cancer Risk Modeling and Assessment Screening and Surveillance Gastric Cancer Risk Modeling and Assessment Screening and Surveillance Esophageal Cancer Risk Modeling and Assessment Esophageal Squamous Cell Carcinoma Barrett Esophagus and Esophageal Adenocarcinoma Screening and Surveillance Head and Neck Squamous Cell Carcinoma Risk Modeling and Assessment Screening Ovarian Cancer Risk Factors and Etiology Screening Endometrial Cancer Risk Factors and Etiology Screening Skin Cancer German SCREEN Study Patient Populations Evidentiary Standards and End Points Other Than Survival Overdiagnosis and Harms of Screening The Way Forward Key References References 24 Nicotine Dependence Summary of Key Points Prevalence of Tobacco Use and Nicotine Dependence in Patients With Cancer Biologic Characteristics and Genetics Diagnosis and Evaluation Current Treatment Recommendations Smoking Among Cancer Patients Barriers to Cessation Treatment in the Oncology Setting Epidemiology and Tobacco Use in Patients With Cancer Reward Pathway and Biologic Characteristics of Addiction Reward Pathway Neuronal Adaptation Genetics Genes Associated With Smoking, Nicotine Dependence, and Lung Cancer Genes Predicting Treatment Outcome Comorbid Conditions Patient Assessment Treatment of Tobacco Use Pharmacologic Interventions Bupropion Varenicline Combinations of First-Line Medications Second-Line Medications Psychosocial Interventions Quitlines Self-Help Materials Cessation Treatments for Patients With Cancer: Availability and Challenges Tobacco Treatment Program at MD Anderson Challenges and Future Directions Key References References F Treatment 25 Cancer Pharmacology Summary of Key Points Fundamental Science Principles of Cancer Drug Action Combinations of Drugs Molecular Imaging of Cancer Drug Action Cancer Drug Delivery: Systemic Exposure Dosage Adjustment Based on Clearance to Achieve Consistent Systemic Exposure Drug-Drug Interactions Drug-Drug Transporter Interactions Interactions Via Self-Medication Oral Cancer Drugs Effect of Food on Systemic Exposure for Oral Drug Delivery Clinical Relevance and Applications Subcutaneous Route of Cancer Drug Delivery Regional Cancer Drug Delivery Brand Names, Generics, Biosimilars New Indications and Repurposing (Repositioning) Clinical Phases of Drug Development Cancer Pharmacology Across the Drug Discovery and Development Process What the Future Holds References 26 Therapeutic Targeting of Cancer Cells Summary of Key Points Molecular Targets Preclinical Development of Molecularly Targeted Anticancer Agents Clinical Development of Molecularly Targeted Anticancer Agents Dose Determination Efficacy Evaluation Use of Pharmacodynamic Markers Rational Use of Functional and Molecular Imaging Patient Selection Rational Approaches to Combination Therapy Conclusions and Future Directions Key References References 27 Basics of Radiation Therapy Summary of Key Points Introduction and Historical Perspective Radiation Physics Radiobiology of Radiation Therapy Clinical Radiation Oncology Planning and Delivery of Radiation Treatment Other Modalities in Radiation Overview of Radiation Physics Nature of Matter and Radiation Interactions of Radiation and Matter Coherent Scatter Photoelectric Effect Compton Scattering Pair Production Photodisintegration Charged Particle Interactions Generation of Therapeutic Radiation Linear Accelerators Radioactive Sources Delivery of Therapeutic Radiation Radiobiology of Radiation Therapy Mechanisms of Radiation Damage to Cells Molecular Biology of Cellular Radiation Responses Cell Survival and Tissue Dose-Response Curves Modifiers of Radiation Sensitivity Clinical Radiation Oncology Therapeutic Ratio Biology of Fractionation Repair Repopulation Reoxygenation Redistribution Radiosensitizers and Radioprotectors Traditional Radiosensitizers Sensitizers of proliferating cells Sensitizers of hypoxic cells Traditional Radioprotectors Chemotherapy Drugs as Radiosensitizers Molecularly Targeted Drugs and Biologics Normal Tissue Toxicity Tolerance Doses Radiation Carcinogenesis Volume Effects Fractionation Sensitivity Clinical Application of the Linear-Quadratic Isoeffect Model Radiation Therapy Delivery Approaches Radiation Therapy Delivery Techniques External Beam Fractionated Radiation Therapy Simulation, treatment planning, and delivery of external beam radiation therapy Intensity-Modulated Radiation Therapy Brachytherapy Simulation, treatment planning, and delivery of brachytherapy Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy Physics of stereotactic radiosurgery and stereotactic body radiation therapy Intraoperative Radiation Therapy Specialized Radiation Therapy Techniques and Facilities Protons Neutrons Heavy ions Future Directions Key References References 28 Hematopoietic Stem Cell Transplantation Summary of Key Points Autologous Hematopoietic Cell Transplantation Allogeneic Hematopoietic Cell Transplantation Histocompatibility and Donor Selection Hematopoietic Stem Cell Sources Conditioning or Preparative Regimens Disease Indications for Hematopoietic Cell Transplantation Acute Myelogenous Leukemia Myelodysplastic Syndromes Chronic Myelogenous Leukemia and Other Myeloproliferative Syndromes Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Non-Hodgkin Lymphoma Hodgkin Lymphoma Multiple Myeloma and Plasma Cell Disorders Solid Tumors Complications of Hematopoietic Cell Transplantation Graft Rejection Engraftment Syndrome Pulmonary Complications Hepatic Complications Renal Complications Cardiovascular Complications Graft-Versus-Host-Disease Infections Secondary Malignancies Conclusions Key References References 29 Gene Therapy in Oncology Summary of Key Points Recent Advances in Gene Therapy Ideal Vector Attributes Current Concerns Regarding Gene Therapy Future Directions of Gene Therapy Vectors Viral Gene Transfer Vectors Retroviridae—Retrovirus Recombinant Moloney murine leukemia virus Recombinant lentivirus Recombinant Adenovirus Recombinant Adeno-Associated Virus Recombinant Herpes Simplex Virus Recombinant Pox Vectors Recombinant Alphavirus Vectors (Sindbis) Nonviral Gene Transfer Vectors Direct DNA Injection/Transduction Hydrodynamic Gene Delivery Liposomes and Virosomes Ballistic Delivery (Gene Gun) Nanoparticles Nucleic Acid–Based Therapeutics DNA Transduction RNA Transduction Oligonucleotides Small Interfering RNA Antisense Ribozymes Gene Targeting Conditional Gene Targeting Tissue-Specific Promoters Tumor-Associated Promoters Telomerase Tumor vasculature Tumor-Specific Promoters Prostate-specific antigen Tyrosinase Conditional Replication and Inducible Promoters Stress-associated genes Multidrug resistance gene (MDR1) Dexamethasone Tetracycline response elements Conditionally Replicative Viruses Conditionally Replicative Adenoviruses Vector Targeting Adenoviral Vectors Structural Modification of the Fiber Protein Modification of the Penton Base Retroviral Vectors Nonviral Vectors Cellular or Targeted Vehicles for Gene Therapy Clinical Trial Strategies Acknowledgments Key References References Self-Assessment Review Questions Answers 30 Therapeutic Antibodies and Immunologic Conjugates Summary of Key Points Effector Mechanisms of Monoclonal Antibodies Cytophilic Monoclonal Antibodies and Antibody-Dependent Cell-Mediated Cytotoxicity Complement Activation Signaling by Agonistic and Antagonistic Antibodies Clinical Application of Naked Monoclonal Antibodies Directed at Cancer Cells (See Table 30.1) Lymphoma and Leukemia Solid Tumors Immune Checkpoint Inhibitors Complications and Contraindications Immunoconjugates Radioimmunoconjugates Compartmental Radioimmunotherapy (See Table 30.4) Multistep Targeting or Pretargeting Immunotoxins and Antibody Drug Conjugates (see Table 30.4) Cellular Immunoconjugates Using Bispecific Antibodies Immunocytokines Immunoenzymes for Antibody-Directed Enzyme Prodrug Therapy Immunoliposomes Improving the Efficacy of Antibody-Based Cancer Therapies Alternative Targets for Anticancer Antibodies Key References References 31 Complementary and Alternative Medicine Summary of Key Points Nutritional Therapeutics Dietary Supplements Legal and Regulatory Issues Contamination and Adulteration Adverse Effects Chaparral (Larrea divaricata Coville) Kava (Piper methysticum) Laetrile Cesium Chloride Aloe Vera Licorice (Glycyrrhiza species) Herbs Containing Aristolochic Acid Adverse Interactions Between Dietary Supplements and Drugs Cytochrome P450 Inducers and Inhibitors St. John’s Wort Green Tea Extract and Its Components Antioxidants Vitamin E Anticoagulant Interactions Cancer Treatment Breast Cancer Nutrition and Physical Activity Low-fat, high–fruit and vegetable diet Soy Mind-Body Approaches Colorectal Cancer Exercise Prostate Cancer Lifestyle Modification During Active Surveillance Symptom and Adverse Effect Management and Quality of Life Pain Acupuncture Postsurgical pain Imagery and Hypnosis Massage Reiki Aromatase Inhibitor–Induced Arthralgia Acupuncture Vitamin D Cachexia Nutritional Therapeutics Fatigue Acupuncture Exercise Yoga Energy Therapies Herbs and Other Dietary Supplements Ginseng Guarana l-Carnitine Sleep Yoga Herbs Nausea and Vomiting Acupuncture and Acupressure Ginger Hypnosis Relaxation and Imagery Neuropathy Acupuncture Herbs and Dietary Compounds Glutamine Glutathione Omega-3 fatty acids Vitamin E Hot Flashes Acupuncture Hypnosis Vitamin E Phytoestrogens Black Cohosh Mucositis Homeopathy Zinc Probiotics Stress Reduction and Quality of Life Aromatherapy Music Expressive Writing Meditation Relaxation and Imagery Massage Xerostomia Acupuncture Cannabis Pain Nausea and Vomiting Appetite and Cachexia Cancer Treatment Information Resources Key References References II Problems Common to Cancer and Therapy A Hematologic Problems and Infections 32 Disorders of Blood Cell Production in Clinical Oncology Summary of Key Points Anemia Pathophysiology Chemotherapy-Induced Anemia Hemolysis Iron Metabolism Blood Loss Management of Anemia Red Blood Cell Transfusion Risks of blood transfusion Erythropoiesis-Stimulating Agents Erythropoiesis-Stimulating Agent Biosimilars Iron Supplementation Neutropenia Pathophysiology Chemotherapy-Related Neutropenia Management of Neutropenia Myeloid Growth Factors Dosing and administration Indications for myeloid growth factors Primary prophylaxis. Duration of myeloid growth factor administration. Secondary prophylaxis. Therapeutic use of myeloid growth factors. Biosimilars Thrombocytopenia Pathophysiology Chemotherapy-Induced Thrombocytopenia Platelet Sequestration Immune-Mediated Thrombocytopenia Management of Thrombocytopenia Platelet Transfusion Risks of platelet transfusion Thrombopoietin First-generation TPO mimetics Thrombopoietic cytokines TPO receptor agonists Conclusion Key References References 33 Diagnosis, Treatment, and Prevention of Cancer-Associated Thrombosis Summary of Key Points Prophylaxis Management Recurrence of Venous Thromboembolism Central Access Catheters Central Nervous System Malignancy Epidemiology of Cancer-Associated Venous Thromboembolism Cancer-Associated Venous Thromboembolism Is Common Bidirectional Relationship Between Cancer and Venous Thromboembolism Venous Thromboembolism Is Associated With Worse Outcomes in Patients With Cancer Pathogenesis of Cancer-Associated Venous Thromboembolism Tumor-Specific Factors Host-Specific Factors Environmental Factors Surgery, Radiation Therapy, and Cancer-Associated Venous Thromboembolism Chemotherapy, Hormonal Therapy, and Cancer-Associated Venous Thromboembolism Immunomodulatory Agents and Cancer-Associated Venous Thromboembolism Molecularly Targeted Therapies and Cancer-Associated Venous Thromboembolism Hematopoietic Growth Factors and Cancer-Associated Venous Thromboembolism Indwelling Venous Catheters and Cancer-Associated Venous Thromboembolism Prevention of Cancer-Associated Venous Thromboembolism Prevention of Venous Thromboembolism in Hospitalized Medical Oncology Patients Prevention of Venous Thromboembolism in Ambulatory Medical Patients With Cancer Assessment of Risk of Cancer-Associated Venous Thromboembolism Prevention of Venous Thromboembolism in Hospitalized Surgical Patients With Cancer Prevention of Central Venous Catheter Thrombosis Diagnosis of Venous Thromboembolism in Patients With Cancer Diagnosis of Cancer-Associated Venous Thromboembolism D-Dimer Testing in the Diagnosis of Venous Thromboembolism Imaging Duplex ultrasonography Contrast venography Computed tomographic venography Magnetic resonance venography Diagnosis of Cancer-Associated Pulmonary Embolism Pulmonary Angiography Ventilation/Perfusion Scanning Computed Tomography Pulmonary Angiography Management of Cancer-Associated Venous Thromboembolism Acute Management Anticoagulation Thrombolysis Vena Cava Filters Newer Anticoagulants Chronic Management of Venous Thromboembolism Management of Recurrent Venous Thromboembolism Management of Central Venous Catheter–Associated Venous Thromboembolism Management of Thrombocytopenic Patients With Associated Venous Thromboembolism Cancer-Associated Venous Thromboembolism in Patients With Central Nervous System Lesions Hematopoietic Stem Cell Transplant and Venous Thromboembolism Outpatient Management of Cancer-Associated Venous Thromboembolism Management of Unsuspected Venous Thromboembolism Use of Anticoagulants to Improve Survival in Patients With Cancer Reversal of Anticoagulation Key References References 34 Infection in the Patient With Cancer Summary of Key Points Neutropenia as a Risk Factor for Infection Other Risk Factors for Infection Sources of Infection Approach to Fever in the Neutropenic Patient Definitions Initial Evaluation Risk Assessment Empiric Antibiotic Therapy Use of Vancomycin or Other Gram-Positive Agents Subsequent Modifications of Empiric Antibiotic Regimens Empiric Antifungal Therapy Discontinuation of Antibiotic Therapy Specific Infections in the Patient With Cancer Bacteremia Pulmonary Infections Fungal Infections Gastrointestinal Infections Upper Gastrointestinal Tract Lower Gastrointestinal Tract Central Nervous System Infections Vascular Access Devices Viral Infections Prevention of Infections in Selected Risk Groups Low-Risk Patients Patients With Acute Leukemia Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Patients With Graft-Versus-Host Disease Prophylaxis With Other Immunosuppressive Therapies Pretransplantation Measures to Prevent Infection Pretransplantation Serostatus Blood Work Environmental Measures to Prevent Infection During and After Transplantation Review of Commonsense Measures That Will Assist in the Prevention of Infection Key References References B Symptom Management 35 Hypercalcemia Summary of Key Points Incidence Etiology Evaluation of the Patient Treatment Calcium Physiology Parathyroid Hormone–Related Peptide 1,25(OH)2D Production Bone Resorption Parathyroid Hormone–Mediated Hypercalcemia Rare Causes of Hypercalcemia of Malignancy Pseudohypercalcemia Tamoxifen Evaluation of the Patient Clinical Manifestations Laboratory Investigations Treatment Restoration of Intravascular Volume and Promotion of Renal Calcium Excretion Reduction of Bone Resorption Bisphosphonates Denosumab Reduction of Intestinal Absorption of Calcium Reduction of Parathyroid Hormone Other Treatments Gallium Nitrate Calcitonin Hemodialysis Long-Term Considerations Key References References 36 Tumor Lysis Syndrome Summary of Key Points Definition and Epidemiology Etiology and Pathogenesis Risk Stratification for Clinical Tumor Lysis Syndrome Risk Stratification—Cancer Factors Risk Stratification—Patient and Presenting Factors Prevention and Management of Tumor Lysis Syndrome Prephase Urine Alkalinization Is Not Warranted in Countries With Access to Rasburicase Reducing Uric Acid Improves Outcomes Allopurinol and Xanthine Production Febuxostat Rasburicase Conclusions References 37 Cancer-Related Pain Summary of Key Points Incidence Etiology of Pain Evaluation of the Patient Treatment Incidence Etiology (Box 37.1) Current Status of Cancer Pain Management Barriers to the Provision of Adequate Analgesia Evaluation of the Patient With Pain Management of Cancer Pain Pharmacologic Therapy Adjuvant Analgesics Antineoplastic Therapy Invasive Therapy Regional Analgesia Neuroablative Procedures Nonpharmacologic Therapy Medical Cannabis Challenges in Pain Management Patients With Pain of Neuropathic Origin Patients With Episodic or Incidental Pain Patients With Impaired Cognitive or Communicative Function Patients With a History of Substance Use Disorder Conclusion Key References References 38 Cancer Cachexia Summary of Key Points Definitions and Epidemiology Biologic Characteristics and Pathophysiology Patient Evaluation and Staging Treatment Future Possibilities and Clinical Trials References 39 Nausea and Vomiting Summary of Key Points Incidence Etiology Evaluation of the Patient Treatment Physiology of the Vomiting Reflex Clinical Features of Chemotherapy-Induced Nausea and Vomiting Clinical Syndromes Acute Nausea and Vomiting Delayed Nausea and Vomiting Anticipatory Nausea and Vomiting Prognostic Factors Chemotherapeutic Agents Patient Characteristics Age Gender History of Alcohol Intake Previous Chemotherapy Conduct and Interpretation of Clinical Antiemetic Trials Treatment of Chemotherapy-Induced Nausea and Vomiting Active Antiemetic Agents 5-HT3 Receptor Antagonists NK1 Receptor Antagonists Corticosteroids Olanzapine Other Antiemetic Agents Combination Antiemetic Therapy—An Integrated Approach Assessment of Emetogenic Risk Selection of a Prophylactic Antiemetic Regimen Anticipatory Nausea and Vomiting Radiation-Induced Nausea and Vomiting Key References References C Treatment Complications 40 Oral Complications Summary of Key Points Incidence Etiology of Complications Prophylactic Measures Treatment Pathophysiology of Mucosal Injury and Clinical Manifestations Mucositis Assessment Oral Complications From Chemotherapy, Including Myeloablative Chemotherapy Incidence and Risk Factors Biologic Therapies Prevention of Chemotherapy-Induced Oral Complications Oral Care Protocols and Oral Hygiene Antimicrobial and Antiseptic Interventions Cryotherapy 5-fluorouracil–based chemotherapy Edatrexate High-dose melphalan Antioxidants, Anticholinergics, and Coating Agents Antiinflammatory Agents Amino Acids Growth Factors Low-Level Laser Therapy Other Interventions Treatment of Chemotherapy-Induced Oral Mucositis Mouthwashes and Coating Agents Antiinflammatory Agents Growth Factors Systemic Analgesics Laser Therapy Other Therapies Treatment for Biologic Therapy–Induced Mucositis Oral Complications From Radiation Therapy Mucositis Etiology of Mucositis Prevention of Mucositis Radiotherapy technique Oral hygiene Humidified air Growth factors Low-level laser therapy Antibiotics and probiotics Benzydamine hydrochloride Sucralfate Amifostine Caphosol Mucoadhesive hydrogel rinse Other interventions Treatment of Established Mucositis Concurrent oral mucosa infection Analgesics Daily nursing evaluation Doxepin rinse “Magic mouthwash” mixes Other interventions Xerostomia Etiology of Xerostomia Prevention of Xerostomia Radiotherapy technique Amifostine Pilocarpine Salivary gland transfer Acupuncture Treatment of Xerostomia Dietary modification Oral lubricants Muscarinic receptor agonists Acupuncture Dental Caries Etiology of Dental Caries Prevention and Treatment of Dental Caries Soft Tissue Necrosis Etiology of Soft Tissue Necrosis Treatment of Soft Tissue Necrosis Osteoradionecrosis Etiology of Osteoradionecrosis Treatment of Osteoradionecrosis Taste Alterations Trismus Etiology of Trismus Prevention and Treatment of Trismus Malignancy Key References References Self-Assessment Questions Answers 41 Dermatologic Toxicities of Anticancer Therapy Summary of Key Points Chemotherapy-Induced Alopecia Cutaneous Extravasation Injury Chemotherapy-Induced Hyperpigmentation Hand-Foot Syndrome Neutrophilic Eccrine Hidradenitis Radiation Dermatitis Radiation Recall Radiation Enhancement Atypical Vascular Lesions and Angiosarcomas Papulopustular Eruption Hand-Foot Skin Reaction Secondary Squamous Neoplasms Cutaneous Complications of Cytotoxic Chemotherapy Chemotherapy-Induced Alopecia Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Differential Diagnosis Treatment Preemptive counseling Preventive treatment Treatments for acceleration of hair growth after chemotherapy Prognosis Cutaneous Extravasation Injury Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Treatment Prevention Pharmacologic and surgical treatment Prognosis Chemotherapy-Induced Hyperpigmentation Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Differential Diagnosis Generalized hyperpigmentation Localized hyperpigmentation Treatment Prognosis Toxic Erythema of Chemotherapy Hand-Foot Syndrome Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Differential Diagnosis Hand-foot skin reaction Acute graft-versus-host disease Erythema multiforme Treatment Dose reductions Prevention Reactive or symptomatic treatment Prognosis Neutrophilic Eccrine Hidradenitis Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Differential Diagnosis Clinical Histologic Treatment Prognosis Cutaneous Complications of Radiation Therapy Radiation Dermatitis Etiology and Biocharacteristics Epidemiology Clinical Manifestations Differential Diagnosis Acute Chronic Diagnosis and Workup Treatment Prognosis Radiation Recall Etiology and Biocharacteristics Epidemiology Clinical Manifestations Differential Diagnosis Cytostatic drug recall Radiosensitization Diagnosis and Workup Treatment Prognosis Radiation Enhancement Etiology and Biocharacteristics Clinical Manifestations Differential Diagnosis Acute radiation-induced dermatitis Diagnosis and Workup Treatment Atypical Vascular Lesions and Angiosarcomas Etiology and Biocharacteristics Epidemiology Clinical Manifestations Differential Diagnosis Diagnosis and Workup Treatment Prognosis Cutaneous Complications of Molecularly Targeted Anticancer Therapy Papulopustular Eruption Etiology and Biocharacteristics Epidemiology Clinical Manifestations Workup Treatment Prophylactic or preemptive treatment Reactive treatment Dose modification Patient education Prognosis Hand-Foot Skin Reaction Etiology and Biocharacteristics Epidemiology Clinical Manifestations Differential Diagnosis Diagnosis and Workup Treatment Prophylactic treatment Reactive treatment Dose modification Prognosis Secondary Squamous Neoplasms Etiology and Biocharacteristics Epidemiology Vemurafenib and dabrafenib Sorafenib Clinical Manifestations Diagnosis and Workup Treatment and Prognosis Vemurafenib and dabrafenib Sorafenib Prevention Key References References 42 Cardiovascular Effects of Cancer Therapy Summary of Key Points Cardiotoxic Effects of Anticancer Agents and Modalities Detecting and Monitoring Cardiac Toxicity Mitigation Strategies Cancer Survivors Cardiotoxic Effects of Anticancer Agents Classification of Cardiotoxicity Temporal Classification Reversibility Anthracycline Toxicity ErbB2 Antagonists Vascular Endothelial Growth Factor Signaling Pathway Inhibitors Proteasome Inhibitors Immunomodulatory Therapy Radiation Therapy Pericarditis Cardiomyopathy Coronary Artery Disease Valvular Abnormalities Detecting and Monitoring Cardiac Toxicity Nonclinical Safety Assessment Adverse Event Reporting and Monitoring in Clinical Trials Biomarkers Troponin Natriuretic Peptides Newer Biomarkers Unanswered Questions About Biomarkers Imaging Strategies Echocardiography Multigated Acquisition Scanning Cardiac Computed Tomography Cardiac Magnetic Resonance Imaging Exercise Testing Endomyocardial Biopsy Genetics Mitigation Strategies Administration of Cancer Therapy Pharmacologic Strategies Nonpharmacologic Strategies Cardiomyopathy Management Cancer Survivors Acknowledgment Key References References 43 Reproductive Complications Summary of Key Points Reproductive Physiology Gonadal Form and Function Hypothalamic-Pituitary-Gonadal Axis Direct Effects of Cancer on Reproductive Function Effects of Cancer Therapy on Sexual and Reproductive Function Surgery Prostate Cancer Testicular Cancer Rectal Cancer Gynecologic Surgery Radiation Therapy Central Nervous System Effects on Reproductive Function Radiation Effects on Testicular Function Radiation Effects on Ovarian Function Pelvic Radiation as a Cause of Reproductive Dysfunction Hormonal Therapy Gonadotropin-Releasing Hormone Agonists and Antagonists Antiandrogens Endocrine Therapy and Breast Cancer Chemotherapy Effects in Men Effects in Women High-Dose Chemotherapy (Stem Cell Transplantation) Effects in Women Effects in Men Markers of Ovarian Reserve Prevention Treatment Hormonal Replacement Management of Erectile Dysfunction Fertility Preservation and Assisted Reproductive Technologies Conclusion Key References References 44 Paraneoplastic Neurologic Syndromes Summary of Key Points Paraneoplastic Syndromes of the Central Nervous System Paraneoplastic Encephalomyelitis Limbic Encephalitis Anti–N-Methyl-d-Aspartate Receptor Encephalitis Anti-γ-Aminobutyric Acid Type A Receptor Encephalitis Paraneoplastic Cerebellar Degeneration Motor Neuron Syndromes Stiff Person Syndrome Peripheral Nerve Hyperexcitability (Neuromyotonia) Paraneoplastic Opsoclonus-Myoclonus Paraneoplastic Syndromes of the Visual System Paraneoplastic Syndromes of the Peripheral Nervous System Paraneoplastic Sensory Neuronopathy Sensorimotor Neuropathies Vasculitic Neuropathy Autonomic Neuropathy Paraneoplastic Syndromes of the Neuromuscular Junction Myasthenia Gravis Lambert-Eaton Myasthenic Syndrome Paraneoplastic Myopathic Syndromes Dermatomyositis and Polymyositis Acute Necrotizing Myopathy Treatment and Prognosis Key References References 45 Neurologic Complications Summary of Key Points Incidence of Chemotherapy- and Radiation Therapy–Induced Neurotoxicity Etiology of Neurotoxicity Evaluation of the Patient Grading of the Complication Treatment Specific Agents Cytosine Arabinoside Cerebellar Toxicity Encephalopathy Spinal Cord Toxicity Liposomal Ara-C Other Neurotoxicity Associated With Cytosine Arabinoside l-Asparaginase Cerebrovascular Events Neuropsychiatric Effects Busulfan Methotrexate Acute Neurotoxicity Subacute Toxicity Chronic Neurotoxicity Spinal Cord Toxicity Vinca Alkaloids Peripheral Neuropathy Central Nervous System Effects Other Toxicity Associated With Vinca Alkaloids Cisplatin Peripheral Neuropathy Spinal Cord Toxicity Other Neurotoxicity Associated With Cisplatin Toxicity Associated With Intraarterial Administration Ototoxicity Oxaliplatin Cyclophosphamide Ifosfamide 5-Fluorouracil Cerebellar Toxicity Neuropsychiatric Symptoms Other Neurotoxicity Associated With 5-Fluorouracil Treatment Fludarabine Nitrosoureas Central Nervous System Toxicity Retinal Toxicity Procarbazine Peripheral Neuropathy Central Nervous System Toxicity Paclitaxel and Docetaxel Tamoxifen Biologic Response Modifiers Interleukin-2 Central Nervous System Toxicity Toxicity Associated With Interleukin-2 Treatment Interferons Central Nervous System Toxicity Peripheral Nervous System Toxicity Thalidomide, Lenalidomide, and Pomalidomide Bevacizumab Ramucirumab Sorafenib Bortezomib Sunitinib Imatinib Rituximab, Ofatumumab, and Obinutuzumab Crizotinib Ibrutinib Brentuximab Vedotin Dinutuximab Blinatumomab Ado-trastuzumab Emtansine Chimeric Antigen Receptor T Lymphocytes Ipilimumab Nivolumab and Pembrolizumab Radiation Neurotoxicity Central Nervous System Effects Acute Toxicity Early-Delayed Toxicity Chronic, Late Radiation Injury Radionecrosis Diffuse Injury Necrotizing Leukoencephalopathy Endocrinologic Effects Indirect Effects of Radiation on the Central Nervous System Radiation Myelopathy Peripheral Nerve Toxicity Muscle Injury From Radiation Treatment Differential Diagnosis Dementia and Encephalopathy Acute Encephalopathy Chronic Encephalopathy and Dementia “Chemobrain” Diagnostic Evaluation Seizures Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Headache Cerebellar Dysfunction Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Cranial Neuropathy Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Optic Neuropathy and Ocular Toxicity Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Spinal Cord Toxicity Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Peripheral Neuropathy Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Myopathy Clinical Manifestations and Differential Diagnosis Diagnostic Evaluation Grading of Neurotoxicity Treatment Prevention Modification of Drug Dosage or Order Protective Agents Recognition of Groups at High Risk for Development of Neurotoxicity Conclusions Key References References 46 Endocrine Complications Summary of Key Points Diagnostic Considerations Evaluation and Treatment Syndrome of Inappropriate Antidiuretic Hormone Secretion Consequences of Surgical Therapy Consequences of Radiation Therapy Hypothalamic-Pituitary Axis Thyroid Parathyroid Glands Role of Systemic Therapy Hypothalamic-Pituitary Axis Thyroid Adrenal Pancreas Role of Biological Agents Evaluation and Treatment of Common Endocrine Dysfunction Hypothalamic-Pituitary Axis Disorders Growth Hormone Deficiency Evaluation Treatment Hyperprolactinemia Evaluation Treatment Thyroid Disorders Evaluation Treatment Syndrome of Inappropriate Antidiuretic Hormone Evaluation Treatment Hyperparathyroidism Evaluation Treatment Adrenal Disorders Evaluation Treatment Surveillance of Childhood Cancer Survivors Conclusion Key References References 47 Pulmonary Complications of Anticancer Treatment Summary of Key Points Radiation-Induced Lung Injury (Radiation Pneumonitis or Fibrosis) Drug-Induced Lung Injury Pulmonary Toxicity of Thoracic Radiation Therapy Incidence of Radiation Lung Injury and Predictive Factors Diagnosis and Management of Radiation Pneumonitis: Acute and Subacute Management of Radiation Pulmonary Fibrosis: Chronic and Late Further Directions in Management and Trials Pulmonary Toxicity of Systemic Anticancer Therapies Cytotoxic Chemotherapy Biologically Targeted Agents Immunotherapy-Related Pulmonary Toxicity Acknowledgment Key References References D Posttreatment Considerations 48 Rehabilitation of Individuals With Cancer Summary of Key Points Epidemiology of Cancer Disability Which Patients Should Be Referred for Cancer Rehabilitation and When? Impairments Pain Fatigue Delirium and Cognitive Dysfunction Mood Disorders Neurologic Impairments Hemiplegia Paraplegia and Tetraplegia Speech, Swallowing, and Nutrition Bone Tumors and Amputations Soft Tissue Impairments Associated With Cancer Diagnoses Bladder and Bowel Management Sexual Function Activity Limitations Activities of Daily Living Exercise for Patients With Cancer Physical Modalities Durable Medical Equipment Participation Restrictions Family and Social Relationships Vocational Rehabilitation Participation in Recreation Transportation Key References References 49 Survivorship Summary of Key Points Present Context of Cancer Survivorship Cancer Survivors in the United States Posttreatment Survivorship Care Detection of Recurrence and Second Cancers Assessment and Treatment of Long-Term and Late Effects Overview of Long-Term and Late Effects Assessment and Treatment of Long-Term and Late Effects Prevention of New or Recurrent Cancers and Late Effects of Cancer Coordination of Cancer Survivorship Care Models of Survivorship Care Survivorship Care Plans Caregivers and Family Members of Cancer Survivors Conclusions Key References References 50 Second Malignant Neoplasms Summary of Key Points Genetic Risks for Subsequent Malignancy Treatment-Associated Risks for Subsequent Malignancies Radiation Therapy Chemotherapy Modifications of Treatment-Related Effects on Subsequent Malignant Neoplasm Risk Environmental Exposures High-Risk Populations for Subsequent Malignancies Childhood Cancer Survivors Sarcomas Hodgkin Lymphoma Survivors Hematopoietic Cell Transplant Survivors Prevention and early detection of subsequent malignancies Conclusions Key References References 51 Caring for Patients at the End of Life Summary of Key Points Distress Hospice Care Grief and Bereavement Communication Needs of Patients and Families Distress Physical Causes Pain Control Death Rattle Dyspnea Xerostomia Exsanguination Psychological Causes Anxiety Depression Delirium Agitation in Dying Patients Social Causes Cultural Considerations Spiritual and Existential Causes Patient Requests for Hastened Death, Legalization of Physician-Assisted Death, and Implications for Oncologists Palliative Sedation for Refractory Symptoms Cannabinoids Hospice Care Clinical Care Provided Levels of Care Medications and Treatments Provided Financial Considerations Grief and Bereavement Key References References E Local Effects of Cancer and Its Metastasis 52 Acute Abdomen, Bowel Obstruction, and Fistula Summary of Key Points Gastrointestinal Perforation Gastrointestinal Bleeding Inflammatory Conditions Gastrointestinal and Biliary Obstruction Fistulae Acute Abdomen: General Considerations Gastrointestinal Perforation Gastrointestinal Bleeding Adverse Events From Anticancer Agents Leading to Bleeding or Perforation Inflammatory Conditions in Patients With Cancer Neutropenic Enterocolitis Appendicitis Pancreatitis Anorectal Conditions in Patients With Cancer Gastrointestinal and Biliary Obstruction General Considerations for Patients With Obstruction Stomach and Duodenum Small Intestine Colon and Rectum Malignant Biliary Obstruction Gastrointestinal Problems After Hematopoietic Stem Cell Transplantation Fistulae References 53 Superior Vena Cava Syndrome Summary of Key Points Etiology Anatomy and Physiology Clinical Features Evaluation Treatment Anatomy and Pathophysiology Etiology Clinical Features Radiographic Findings and Diagnostic Studies Imaging Studies Diagnostic Approach Treatment Radiotherapy Treatment Intent Dose Fractionation Total Dose Radiation Therapy Treatment Volume and Technology Response to Radiotherapy Chemotherapy Small Cell and Non–Small Cell Lung Cancer Non-Hodgkin Lymphoma Stents Surgery Supportive Measures Summary Key References References 54 Spinal Cord Compression Summary of Key Points Incidence Etiology Evaluation Treatment Epidemiology Etiology Clinical Manifestations Back Pain Muscle Weakness Altered Sensation Autonomic Dysfunction Patient Evaluation Treatment (Fig. 54.2) Medical Therapy Surgery Conventional External Beam Palliative Radiotherapy Stereotactic Body Radiation Therapy Conclusions Key References References 55 Brain Metastases and Neoplastic Meningitis Summary of Key Points Incidence Diagnosis Prognosis Treatment Brain Metastases Epidemiology Prevention and Early Detection Pathophysiology Clinical Presentation Diagnosis Prognostic Factors Treatment Corticosteroids Anticonvulsant Agents Definitive Treatment Surgery Radiation Therapy Whole-Brain Radiotherapy Stereotactic Radiosurgery Localized Treatment: Surgery or Stereotactic Radiosurgery Selected Studies of Treatment of Brain Metastases: From Whole-Brain Radiotherapy to Surgery and Stereotactic Radiosurgery Selected randomized trials of various fractionations for whole-brain radiotherapy alone Randomized trials of whole-brain radiotherapy with or without surgery Randomized trial of surgery with or without whole-brain radiotherapy Randomized trial of stereotactic radiosurgery with or without whole-brain radiotherapy Randomized trials of whole-brain radiotherapy with or without stereotactic radiosurgery Stereotactic radiosurgery dose considerations Multiple Metastases Fractionated Stereotactic Radiation Stereotactic Radiation to Resection Cavity Preoperative Stereotactic Radiation Stereotactic Radiation for Older Adult Patients Treatment-Related Toxicity Toxicity of surgery Toxicity of whole-brain radiotherapy Neurocognitive toxicity Toxicity of stereotactic radiosurgery Systemic Therapy Chemotherapy Molecularly Targeted Therapy Follow-up and Salvage Therapy Neoplastic Meningitis Epidemiology Pathophysiology Clinical Presentation Diagnosis Radiologic Evaluation Cerebrospinal Fluid Evaluation Prognostic Factors Treatment Radiation Therapy Intrathecal Chemotherapy Systemic Therapy Concurrent Chemoradiation Treatment-Related Toxicity Disease Response Assessment Key References References 56 Bone Metastases Summary of Key Points Incidence Causes Diagnosis Evaluation of the Patient Treatment Complications Incidence Primary Tumors Leading to Bone Metastases Causes Initiation of Bone Metastases Pathogenesis Bone Remodeling Tumor Cell–Bone Cell Interactions Osteolytic Bone Disease Osteoblastic Bone Disease Myeloma Bone Disease Diagnosis Differential Diagnosis Diagnostic Methods Skeletal Radiography Radionuclide Bone Scan Computed Tomography Magnetic Resonance Imaging Positron Emission Tomography Biochemical Markers of Bone Metabolism Bone Markers in Diagnosis of Bone Metastases and as Predictive and Prognostic Indicators Assessment of Patient Response to Treatment of Metastatic Bone Disease Assessment of Symptoms and Activity Status Imaging to Assess Response in Bone Metastases Tumor Markers Biochemical Assessment of Response Treatment External-Beam Radiation Therapy Targeted Radioisotope Therapy Systemic Therapy Bisphosphonates Rationale for the Wider Use of Bisphosphonates Bisphosphonates to Prevent Skeletal Morbidity and Relief of Bone Pain Breast cancer Multiple myeloma Prostate cancer Other tumors Disease-Modifying Effects of Bisphosphonates Adverse Events RANKL Inhibition to Prevent Skeletal Morbidity Optimum Use of Bone-Targeted Agents in Persons With Metastatic Bone Disease New Targeted Therapies in the Treatment of Metastatic Bone Disease Protecting the Skeleton Prevention of Bone Metastases Effects of Cancer Treatments on Skeletal Health Bone Loss in Breast Cancer Bone Loss in Prostate Cancer Complications of Bone Metastases Bone Pain Hypercalcemia of Malignancy Pathological Fractures Spinal Instability Compression of the Spinal Cord or Cauda Equina Summary Key References References 57 Lung Metastases Summary of Key Points Background and Etiology Diagnostic Evaluation Definitive Management: Non-surgical Interventions Definitive Management: Surgical Resection Survival After Metastasectomy Complications of Lung Metastases Background and Etiology Pathogenesis of Lung Metastasis Effect of Diet on Lung Metastasis Diagnostic Evaluation Computed Tomography Nuclear Imaging Definitive Management of Pulmonary Metastases Radiation Therapy Radiofrequency Ablation Stereotactic Body Radiation Therapy Surgical Management Lung metastasectomy. Video-Assisted Thoracoscopic Surgery Versus Thoracotomy (Figs. 57.7 and 57.8) Survival After Metastasectomy Colorectal Cancer Bone and Soft Tissue Sarcoma Melanoma Renal Cell Carcinoma Head and Neck Cancer Germ Cell Tumors Breast Cancer Giant Cell Tumors of Bone Complications of Lung Metastases Bronchial Obstruction Malignant Pleural Effusion Key References References 58 Liver Metastases Summary of Key Points Etiology Diagnostic and Preoperative Evaluation Management of Colorectal Liver Metastases Management of Noncolorectal Liver Metastases Diagnostic and Preoperative Evaluation Clinical Risk Scores Computed Tomography Magnetic Resonance Imaging Positron Emission Tomography Intraoperative Ultrasonography Percutaneous Biopsy Evaluation of the Future Liver Remnant Diagnostic Laparoscopy Management of Colorectal Metastases Survival Rate Prediction Management of Surgically Resectable Colorectal Metastases Surgical Resection of Liver Metastases Patient Selection Anatomic Considerations Control of Blood Loss Current Surgical Controversies in Metastatic Colorectal Cancer Does Tumor Size or Number Matter? Is Anatomic Resection Superior to Nonanatomic Resection? Does the Margin Distance Matter? Can Simultaneous Colectomy and Hepatectomy Be Performed? Is Extrahepatic Disease a Contraindication to Liver Resection? Can Laparoscopic Surgery Be Performed Without Compromising Oncologic Outcomes? Does Newer Technology Make Parenchymal Dissection Safer? Systemic Therapy Systemic Therapy for Resectable Disease Systemic Therapy for Unresectable Disease: Conversion to Resectability Neoadjuvant Chemotherapy Portal Vein Embolization Two-Stage Hepatectomy Management of Unresectable Liver Metastases Chemotherapy Fluoropyrimidines FOLFOX FOLFIRI FOLFOXIRI Epidermal Growth Factor Receptor Monoclonal Antibodies Bevacizumab Liver-Directed Therapy Radiofrequency Ablation Microwave Ablation Hepatic Artery Infusion Yttrium-90 Radioembolization Cryotherapy Percutaneous Ethanol Ablation Chemotherapy After Resection Surveillance Treatment of Recurrent Disease Management of Noncolorectal Liver Metastases Neuroendocrine Gastrointestinal Stromal Tumors Other Liver Metastases Conclusions Key References References 59 Malignancy-Related Effusions Summary of Key Points Malignancy-Related Ascites Evaluation Treatment Malignant Pericardial Effusion Evaluation Treatment Malignancy-Related Pleural Effusion Evaluation Treatment Malignancy-Related Ascites Etiology and Pathogenesis Diagnosis and Evaluation History and Physical Examination Imaging Studies Diagnostic Paracentesis Surgical Approaches Management Diuretics Large-Volume Paracentesis Drainage Catheters Peritoneovenous Shunting Intraperitoneal Therapy Biological Therapy Immunotherapy Targeted therapy Radioisotopes Malignant Pericardial Effusions Etiology and Pathogenesis Evaluation and Diagnosis History and Physical Examination Pericardiocentesis and Fluid Analysis Imaging Management Pericardiocentesis Intrapericardial Therapies Systemic Chemotherapy Surgical Procedures Percutaneous Balloon Pericardiotomy Radiation Therapy Malignant Pleural Effusions Etiology and Pathogenesis Evaluation and Diagnosis History and Physical Examination Imaging Studies Diagnostic Thoracentesis and Pleural Fluid Analysis Pleural Biopsy Management Therapeutic Large-Volume Thoracentesis Pleurodesis Indwelling Pleural Catheters Pleuroperitoneal Shunts Pleurectomy Systemic Chemotherapy and Radiotherapy Key References References F Special Populations 60 Cancer in the Elderly Summary of Key Points Physiologic Changes of Aging Geriatric Assessment in Oncology Clinical Applications of the Geriatric Assessment What the Future Holds Fundamental Science Physiologic Changes of Aging Geriatric Assessment in Oncology Functional Status Comorbidity Polypharmacy Nutritional Status Cognitive Function Psychological Status Social Support Clinical Relevance and Applications Estimating Survival Predicting Chemotherapy Toxicity Modifying and Adapting Treatment Plans Effect on Nononcologic Treatments Effect on Oncologic Treatments Cancer Prevention and Screening in Older Adults Examples of Cancer Prevention in Older Adults Cancer Screening Recommendations in Older Adults What the Future Holds Innovative Trial Designs and Outcomes Biomarkers of Aging Implementation of Geriatric Assessment- based Care Dedication Key References References Annotated Online Resources 61 Special Issues in Pregnancy Summary of Key Points Fetal Development and Physiology Maternal Physiology: Relevance to Chemotherapy and Surgery Diagnostic Radiology for Staging Ultrasonography, Computed Tomography, and Magnetic Resonance Imaging Position Emission Tomography Scanning Teratogenicity of Chemotherapy Specific Chemotherapy Drugs Antimetabolites Alkylating Agents Platinum Derivatives Taxanes Vinca Alkaloids Anthracyclines Monoclonal Antibodies Tyrosine Kinase Inhibitors Other Agents Supportive Care Chemotherapy in Pregnancy: Overview Chemotherapy Dosing Specific Malignancies Breast Cancer Cervical Cancer Melanoma Ovarian Cancer Malignant Gestational Trophoblastic Disease Colorectal Cancer Thyroid Cancer Other Cancers Hematologic Malignancies Hodgkin Lymphoma Non-Hodgkin Lymphoma Acute Leukemia Chronic Leukemias Other Considerations Therapeutic Abortion Timing of Delivery Therapeutic Radiation Subsequent Pregnancy Transfer of Maternal Disease to the Fetus Conclusion Key References References 62 Human Immunodeficiency Virus (HIV) Infection and Cancer Summary of Key Points Kaposi Sarcoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Diagnosis, and Staging Treatment Future Possibilities and Clinical Trials HIV-Associated Lymphomas Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Treatment Diffuse Large B-Cell Lymphoma Primary Central Nervous System Lymphoma Burkitt Lymphoma Primary Effusion Lymphoma Plasmablastic Lymphoma Hodgkin Lymphoma Relapsed Lymphoma and Hematopoietic Stem Cell Transplantation Controversies and Challenges Future Possibilities and Clinical Trials Anal and Cervical Cancers Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Primary Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Challenges, Future Possibilities, and Clinical Trials Other Non–AIDS–Defining Malignancies Cancer Prevention and Screening in HIV Infection Key References References Annotated Online Resources III Specific Malignancies A Central Nervous System 63 Cancer of the Central Nervous System Summary of Key Points Incidence Pathology and Classification Clinical Manifestations Diagnostic Studies Therapy Epidemiology Tumor Biology Cell Proliferation Invasion Angiogenesis and Hypoxia Stem Cells Clinical Presentation Pathophysiology of Signs and Symptoms General Signs and Symptoms Localizing Signs of Intracranial Tumors Treatment of Brain Tumor Symptoms Acute Raised Intracranial Pressure Chronically Increased Intracranial Pressure Seizures Deep Venous Thrombosis Diagnostic Imaging Magnetic Resonance Imaging Computed Tomography Imaging of Supratentorial Gliomas Positron Emission Tomography Challenges to Imaging Modalities Lumbar Puncture Surgery: General Considerations Radiation Therapy: General Considerations Radiation Therapy: Technical Details Stereotactic Radiotherapy Intensity-Modulated Radiation Therapy Heavy Charged Particle Radiation Therapy Adverse Effects After Irradiation of the Brain or Spine Acute and Early Delayed Effects After Cranial Irradiation Late Effects Radiation Necrosis of the Brain Neurocognitive Deficits After Cranial Irradiation Endocrine Deficits After Cranial or Spinal Irradiation Optic Neuropathy After Cranial Irradiation Second Malignant Neoplasms Developing After Cranial Irradiation Myelopathy After Spinal Irradiation General Principles of Chemotherapy Supratentorial Gliomas Clinical Considerations Pathologic Classification of Supratentorial Gliomas Histologic Classification of Supratentorial Gliomas Molecular Classification of Supratentorial Gliomas Isocitrate Dehydrogenase Mutations 1p19q Codeletion in Oligodendroglioma Genome Level Classification of Glioblastoma Other Genetic Changes in Glioblastomas Surgery for Supratentorial Gliomas: Extent of Surgical Resection Navigation During Surgery Complications of Surgery Radiation Therapy for Supratentorial Gliomas Radiation Therapy for Low-Grade Gliomas Radiation Therapy for High-Grade Gliomas Tumor-Treating Fields for Glioblastoma Chemotherapy for Gliomas Chemotherapy for Newly Diagnosed High-Grade Astrocytomas Chemotherapy for Recurrent High-Grade Astrocytomas Chemotherapy in Addition to Radiotherapy for Low-Grade Astrocytomas Chemotherapy for Low-Grade Oligodendrogliomas and Oligoastrocytomas Chemotherapy for Newly Diagnosed Anaplastic Oligodendrogliomas Chemotherapy for Recurrent Anaplastic Oligodendroglioma Therapy for Elderly Patients With Malignant Gliomas Quality of Life After Therapy for Gliomas New Approaches to Therapy of Gliomas Adult Brainstem Gliomas Primary Central Nervous System Lymphoma Histopathologic Features Tumor Biology Clinical Diagnosis and Staging Treatment Meningioma Clinical and Pathologic Considerations Grading of Meningiomas Surgery and Conventional Radiation Therapy for Meningiomas Stereotactic Radiation Techniques for Meningiomas Medical Therapy for Meningiomas Pituitary Adenoma Clinical and Pathologic Considerations Surgery for Pituitary Adenomas Medical Therapy for Prolactinomas Radiation Options for Pituitary Adenomas Stereotactic Radiosurgery for Pituitary Adenomas Late Effects After Pituitary Irradiation Acoustic Neuroma Clinical and Pathologic Considerations Surgery for Acoustic Neuromas Radiation Treatment Options for Acoustic Neuromas Cerebellar Hemangioblastomas Clinical and Pathologic Considerations Therapy for Cerebellar Hemangioblastomas Chordomas and Chondrosarcomas Involving the Base of the Skull Clinical and Pathologic Considerations Therapy for Chordomas and Chondrosarcomas Involving the Base of the Skull Glomus Tumors of the Base of the Skull Clinical and Pathologic Considerations Therapy for Glomus Tumors of the Base of the Skull Pineal Region Tumors Tumors of the Spinal Axis Clinical and Pathologic Considerations Chordomas Involving the Spinal Axis Spinal Meningiomas Spinal Schwannomas Spinal Cord Ependymomas Spinal Cord Astrocytomas Miscellaneous Intramedullary Tumors Childhood Brain Tumors Embryonal Brain Tumors in Childhood Medulloblastoma Atypical Teratoid Rhabdoid Tumors Childhood Gliomas Diffuse Midline Gliomas Low-Grade Astrocytomas of Childhood Ependymoma Intracranial Germ Cell Tumors Craniopharyngioma Brain Tumors in Infants Key References References B Head, Neck, and Eye 64 Ocular Tumors Summary of Key Points Incidence Etiology Diagnosis Treatment (Fig. 64.1) Intraocular Tumors (Box 64.1) Uveal Melanoma Etiology and Biologic Characteristics Pathology and Pathways of Spread Clinical Manifestations and Patient Evaluation Treatment Metastatic Surveillance Treatment of Metastatic Disease Retinoblastoma Pathogenesis Clinical Features Differential Diagnosis Management Intraocular Lymphomas Primary Vitreoretinal Lymphoma Epidemiology Pathology Clinical manifestations Treatment Uveal Lymphoma Ocular Leukemia Etiology Clinical manifestations Treatment Choroidal Metastasis Epidemiology Clinical Manifestations Treatment Paraneoplastic Conditions Conjunctival Tumors (Box 64.2) Conjunctival Squamous Cell Carcinoma Pathogenesis Clinical Features Differential Diagnosis Management Conjunctival Malignant Melanoma Pathogenesis Clinical Features Differential Diagnosis Management Eyelid Tumors (Box 64.3) Basal Cell Carcinoma of the Eyelid Pathogenesis Clinical Features Differential Diagnosis Management Squamous Cell Carcinoma of the Eyelid Pathogenesis Clinical Features Differential Diagnosis Management Sebaceous Gland Carcinoma of the Eyelid Pathogenesis Clinical Features Differential Diagnosis Management Orbital Tumors (Box 64.4) Orbital Lymphoma Pathogenesis Clinical Features Differential Diagnosis Management Lacrimal Gland Tumors Pathogenesis Clinical Features Differential Diagnosis Management Orbital Meningioma Pathogenesis Clinical Features Differential Diagnosis Management Optic Pathway Glioma Pathogenesis Clinical Features Differential Diagnosis Management Key References Melanoma Retinoblastoma Intraocular lymphoma Choroidal Metastasis Imaging intraocular tumors Squamous cell carcinoma of the conjunctiva Conjunctival melanoma Basal cell carcinoma Squamous cell carcinoma Sebaceous gland carcinoma Orbital lymphoma Lacrimal gland tumors Optic nerve sheath meningiomas Optic pathway gliomas References 65 Cancer of the Head and Neck Summary of Key Points Clinical Presentation and Patient Evaluation Initial Head and Neck Examination Staging Investigations Follow-up Program Molecular and Genetic Aspects of Head and Neck Squamous Cell Carcinoma Treatment Overview Defining Treatment Algorithms: Primary Site Defining Treatment Algorithms: Management of the Neck Second Primary Tumors Surgery Neck Dissection Radiation Therapy Postoperative Radiation Therapy Proton Beam Therapy Brachytherapy Neoadjuvant and Induction Chemotherapy Concurrent and Concomitant Chemoradiotherapy Sequential Therapy Nutrition Considerations Specific Anatomic Sites Nasopharyngeal Carcinoma Anatomy Epidemiology Histology and Pathology Diagnostic and Staging Workup Prognostic Factors Treatment Strategy Treatment-Related Toxicities Nasal Cavity and Paranasal Sinus Cancer Histology and Pathology Diagnostic and Staging Workup Treatment Strategy Treatment Outcomes and Related Toxicities Oral Cavity Histology and Pathology Diagnostic and Staging Workup Treatment Strategy Lip Buccal mucosa Oral tongue Floor of mouth Hard palate Oropharynx Anatomy Epidemiology Presentation, Workup, and Staging Treatment Early-stage disease Transoral robotic surgery Advanced-stage disease Major and Minor Salivary Gland Cancer Histology and Pathology Mucoepidermoid carcinoma Adenocarcinoma, not otherwise specified Adenoid cystic carcinomas Acinic cell carcinoma Mammary analogue secretory carcinoma Carcinoma ex pleomorphic adenoma Polymorphous low-grade carcinoma Salivary duct carcinoma Myoepithelial carcinoma Staging Treatment Strategy Larynx Epidemiology Histology Presentation, Workup, and Staging Treatment Hypopharynx Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Key References References Self-Assessment Review Questions Answers C Skin 66 Melanoma Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy Adjuvant Therapy Treatment of Metastatic Disease Epidemiology Risk Factors for Melanoma Demographic and Phenotypic Risk Factors Environmental Risk Factors: Ultraviolet Radiation and Sun Exposure Presence of Nevi or Atypical Nevi Personal History of Melanoma or Nonmelanoma Skin Cancer Family History Role of Genetic Testing Etiology and Biologic Characteristics Biology RAS, RAF and MAP Kinase Pathway KIT Prevention and Early Detection Primary Prevention Secondary Prevention Pathology and Pathways of Spread Melanoma Histopathology Clinical Manifestations, Patient Evaluation, and Staging Clinical Presentation Superficial Spreading Melanoma Lentigo Maligna and Lentigo Maligna Melanoma Nodular Melanoma Acral Lentiginous Melanoma Desmoplastic Melanoma Biopsy Technique Prognostic Factors and Microstaging TNM Criteria for Staging Patient Evaluation Treatment for Primary Localized Melanoma Management of the Primary Lesion Management of Regional Lymph Nodes Systemic Adjuvant Therapy Locally Advanced Disease Local Recurrence In-Transit Disease Nodal Recurrence Isolated Limb Perfusion or Infusion Neoadjuvant Therapy Surveillance After Primary Therapy Treatment of Metastatic Disease Diagnosis and Evaluation Molecularly Targeted Therapy Immunotherapy Chemotherapy Biochemotherapy Role of Radiation in Advanced Melanoma Role of Surgery in Advanced Melanoma Summary for Treatment of Metastatic Disease Palliative Care Special Clinical Situations in Stage IV Disease Brain Metastasis Other Clinical Issues and Clinical Sites of Melanoma Unknown Primary Site Ocular Melanoma Mucosal Melanoma Controversies, Challenges, and Future Possibilities Clinical Trials Key References References 67 Nonmelanoma Skin Cancers Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy and Results Locally Advanced and Metastatic Disease Palliation Best Practices for Patient Screening and Tumor Prevention When and How to Perform Biopsy Genetics of Nonmelanoma Skin Cancer Fundamental Science and Clinical Relevance Hedgehog Signaling Pathway p53 Mutations ras Mutations Mutations of Other Genes Predisposing to Nonmelanoma Skin Cancers What the Future Holds Basal Cell Carcinoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Primary Therapy Treatment of Locally Advanced and Metastatic Disease Challenges and Future Possibilities Squamous Cell Carcinoma and Bowen Disease Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Treatment of Locally Advanced and Metastatic Disease Challenges and Future Possibilities Keratoacanthoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Future Possibilities and Clinical Trials Nonmelanoma Skin Cancer in Immunocompromised Hosts Epidemiology Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Future Possibilities and Clinical Trials Sebaceous Carcinoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Treatment of Locally Advanced and Metastatic Disease Merkel Cell Carcinoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Treatment of Locally Advanced Disease and Palliation Treatment of Metastatic Disease Challenges and Future Possibilities Dermatofibrosarcoma Protuberans Epidemiology Etiology and Biologic Characteristics Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Locally Advanced Disease and Palliation Challenges and Future Possibilities Cutaneous Angiosarcoma Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, Staging Primary Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Challenges and Future Possibilities Key References References D Endocrine 68 Cancer of the Endocrine System Summary of Key Points Thyroid Cancer Medullary Thyroid Cancer Adrenocortical Cancer Malignant Pheochromocytoma Multiple Endocrine Neoplasia Syndromes Carcinoid Tumors Pancreatic Neuroendocrine Tumors Parathyroid Carcinoma Thyroid Cancer Incidence Classification Etiology Classification and Prognosis Diagnosis Laboratory Studies Fine-Needle Aspiration Biopsy Imaging Treatment Surgery Radioactive Iodine Thyroxine Suppression External Beam Radiation Chemotherapy Recurrence Surveillance Treatment of Recurrent Disease Medullary Thyroid Cancer Diagnosis Treatment Adrenocortical Cancer Incidence Pathogenesis Clinical Presentation Diagnosis Treatment Primary Disease Surgery Mitotane Chemotherapy Radiotherapy Hormonal control Recurrent or Metastatic Disease Prognosis Malignant Pheochromocytoma Incidence Pathogenesis Clinical Presentation Diagnosis Treatment Surgery 131I-MIBG Chemotherapy Radiotherapy Hormonal Control Future Drugs Prognosis Multiple Endocrine Neoplasia Syndromes Multiple Endocrine Neoplasia Type 1 Clinical Features Genetics and Diagnosis Treatment Multiple Endocrine Neoplasia Type 2 Clinical Features Genetics and Diagnosis Management Carcinoid Tumors Incidence Clinical Pathology and Staging Anatomy Diagnosis Symptoms Carcinoid Syndrome Flushing Diarrhea Heart Disease Therapy Surgery Radiation Therapy Antihormonal Therapy Chemotherapy Interferon Hepatic-Directed Therapy Targeted Agents Radionuclide Therapy Pancreatic Neuroendocrine Tumors Diagnosis and Imaging Staging Specific Pancreatic Neuroendocrine Tumor Subtypes Insulinoma Glucagonoma Somatostatinoma Gastrinoma Tumors Secreting Vasoactive Intestinal Peptide Therapy Radiation Therapy Liver-Directed Therapy Somatostatin Analogue Interferon Chemotherapy Targeted Therapy Parathyroid Carcinoma Incidence Etiology Clinical Characteristics Diagnosis Treatment Surgical Therapy Medical Therapy Adjuvant Therapy Genetic Counseling Outcomes Key References References E Thoracic 69 Cancer of the Lung Summary of Key Points Non–Small Cell Lung Cancer Small Cell Lung Cancer Epidemiology Risk Factors Smoking Cessation Pathology Tissue and Cytologic Diagnosis of Lung Cancer Squamous Cell Carcinoma Adenocarcinoma Other Non–Small Cell Carcinomas Neuroendocrine Tumors of the Lung Large Cell Neuroendocrine Carcinoma Small Cell Carcinoma Typical Carcinoid Tumor Atypical Carcinoid Tumor Immunohistochemistry of Lung Tumors Biology of Lung Cancer Early Detection and Screening High-Risk Population: A Susceptible Subgroup Imaging Approach Low-Dose Spiral Computed Tomography Scan Positron Emission Tomography Other Imaging Techniques Biofluid-Based Biomarkers for Lung Cancer Clinical Presentation Presenting Signs and Symptoms Paraneoplastic Disorders Hypercalcemia Hyponatremia and the Syndrome of Inappropriate Antidiuretic Hormone Ectopic Adrenocorticotropic Hormone Production Neurologic Paraneoplastic Syndromes Diagnostic Workup and Staging Assessment of Intrathoracic Disease Assessment of Extrathoracic Disease Solitary Pulmonary Nodule Non–Small Cell Lung Cancer Presurgical Evaluation Physiologic Evaluation Smoking Cessation Nutritional Status Impact of Age Spirometry and Pulmonary Diffusion Capacity Cardiopulmonary Exercise Testing Quantitative Perfusion Study Cardiovascular Status Effects of Induction Chemotherapy Presurgical Evaluation Summary Surgical Management of Non–Small Cell Lung Cancer Occult Lung Cancer Stage I Lung Cancer Other Local Control Techniques Stage II Lung Cancer Mainstem bronchus tumors Superior sulcus tumors Direct mediastinal involvement Chest wall invasion Stage IIIA Locally Advanced Lung Cancer Incidental N2 disease Clinically evident N2 disease Unresectable N2 disease Resection of T4 disease Carinal resection Other mediastinal structures Stage IIIB and IIIC Locally Advanced Lung Cancer Adjuvant Chemotherapy Adjuvant Radiation Therapy or Postoperative Radiation Therapy Neoadjuvant Chemotherapy Neoadjuvant Chemoradiation Therapy Surgery in Stage IV Non–Small Cell Lung Cancer Malignant Pleural Effusions Second Primary Tumors or Metastasis Treatment of Locally Advanced Unresectable Non–Small Cell Lung Cancer Concurrent Chemoradiation Versus Radiation Alone Sequential Versus Concurrent Chemoradiation Therapy Optimal Radiation Therapy Dose for Concurrent Chemoradiotherapy Concurrent Chemoradiation Therapy With Consolidation or Induction Chemotherapy Optimal Chemotherapy Regimen in Stage III Non–Small Cell Lung Cancer Modulation of Concurrent Chemoradiation Therapy Toxicity Molecular Targeted Combined-Modality Therapy Immunotherapy in Locally Advanced NSCLC Metastatic Non–Small Cell Lung Cancer Newer Versus Older Platinum-Based Doublet Drug Combinations Triplet Versus Doublet Platinum-Based Drug Combinations Duration of Therapy Cisplatin Versus Carboplatin Platinum- Versus Non–Platinum-Containing Chemotherapy Chemotherapy for Palliation of Symptoms Elderly Patients Patients With Poor Performance Status Second-Line Therapy Molecular Alterations in Lung Cancer Patients Epidermal growth factor receptor Monoclonal antibodies to epidermal growth factor receptor ALK fusions ROS1 fusions RET fusions ERBB2 MET KRAS RAF Vascular Endothelial Growth Factor Inhibitors Immunotherapy in Lung Cancer Summary: Metastatic Non–Small Cell Lung Cancer Small Cell Lung Cancer Small Cell Lung Cancer Staging Prognostic Factors Treatment of Small Cell Lung Cancer Chemotherapy Overview: Emergence of Etoposide and Cisplatin Extensive-stage small cell lung cancer Additional active agents with etoposide and cisplatin Active agents substitutions in etoposide and cisplatin therapy Etoposide and cisplatin dose intensification Weekly administration of etoposide and cisplatin with additional active agents Maintenance therapy Limited-Stage Small Cell Lung Cancer Combined-modality therapy for limited-stage small cell lung cancer Timing of thoracic radiation therapy Duration of combined-modality therapy Fractionation of thoracic radiation therapy Dose of thoracic radiation therapy Target volume for thoracic radiation therapy Surgery in Small Cell Lung Cancer Prophylactic Cranial Irradiation Small Cell Lung Cancer in Elderly Patients and Those With Poor Performance Status Second-Line Chemotherapy in Small Cell Lung Cancer Novel and Targeted Therapy in Small Cell Lung Cancer Key References References Self-Assessment Review Questions Answers 70 Diseases of the Pleura and Mediastinum Summary of Key Points Malignant Pleural Mesothelioma Thymoma Malignant Pleural Effusions Primary Tumors of the Pleura: Mesothelioma Epidemiology Clinical Presentation Pathology Staging Surgical Evaluation and Resection Chemotherapy Chemotherapy for Patients With Resectable Malignant Pleural Mesothelioma Radiation Therapy Radiation Therapy as Prophylaxis Radiotherapy as a Component of Radical Treatment Extrapleural Pneumonectomy and Adjuvant Radiotherapy Preoperative Radiation Therapy in the Definitive Setting Radiation Therapy for Palliation Diseases of the Mediastinum Anterior Mediastinal Mass: Thymoma Surgical Resection for Thymoma Radiation Therapy for Thymoma Thymic Carcinoma Thymic Carcinoid Nonmalignant Thymic Tumors Tumors of the Middle Mediastinum Posterior Mediastinal Tumors Pleural Effusions Management of Malignant Pleural Effusions Key References References 71 Cancer of the Esophagus Summary of Key Points Classification Incidence Pathogenesis Diagnosis and Staging Treatment Algorithm Metastatic or Recurrent Disease Histologic and Molecular Classification and Location Incidence Pathogenesis Clinical Risk Factors Adenocarcinoma: Role of Gastroesophageal Reflux Disease and Barrett Esophagus Diagnostic and Staging Evaluation Choice of Therapeutic Options: Barrett Esophagus and Dysplasia Chemotherapy Single-Agent Chemotherapy Combination Chemotherapy Fluoropyrimidine/Platinum Doublet Moving Beyond 5-Fluorouracil–Cisplatin Anthracyclines Taxanes Irinotecan Second-Line Chemotherapy Response Rates in Adenocarcinoma and Squamous Cell Carcinoma Targeted Therapy Anti-HER2 Therapy Trastuzumab Other Anti-HER2 Therapies Anti–Vascular Endothelial Growth Factor Therapy Bevacizumab Ramucirumab Anti-Vascular Endothelial Growth Factor Receptor–2 Tyrosine Kinase Inhibitors Anti-Epidermal Growth Factor Receptor Therapy Immunotherapy Immune Checkpoints Anti-PD-1 Antibodies Choice of Therapeutic Options: Localized Esophageal Cancer Surgery Alone Choice of Therapeutic Options: Early Esophageal Cancer Nonsurgical Management of Early-Stage (Tis, Ia) Esophageal Cancer Esophagectomy for Stage I and IIa Tumors Choice of Therapeutic Options: Locally Advanced Esophageal Cancer Transhiatal Resection Ivor Lewis Approach Left Thoracoabdominal Approach Multiple Incisions Radical Resections Minimally Invasive Esophagectomy Survival After Surgery Alone Perioperative Chemotherapy and Surgery Chemotherapy After Surgery Preoperative Chemoradiation and Surgery Standard Approaches Intensification of Combined Modality Therapy Neoadjuvant Chemotherapy Intensification of the Radiation Dose Intraluminal Brachytherapy External-Beam Radiotherapy Preoperative Chemoradiation for Early-Stage Disease Preoperative Chemoradiation Versus Chemotherapy Postoperative Chemoradiation Is Surgery Necessary After Combined Modality Therapy? Positron Emission Tomography–Directed Therapy Management of Tracheoesophageal Fistula Cervical Esophageal Cancer Treatment of Dysphagia Chemotherapy and Radiation Endoscopic Techniques Key References References F Gastrointestinal 72 Cancer of the Stomach Summary of Key Points Epidemiology and Pathology Biological Characteristics Staging Evaluation Primary Therapy Adjuvant Therapy Palliation Treatment of Metastatic Disease Algorithm Etiology and Biological Characteristics Etiology Biological Characteristics Histology Prognostic Factors Geographic Variation Molecular Biology Prevention and Early Detection Clinical Manifestations, Patient Evaluation, and Staging Surgery Survival After Surgery Alone Relapse Patterns After “Curative Resection” Perioperative Chemotherapy Poor Pathologic Response to Preoperative Chemotherapy Postoperative Chemoradiation D0 or D1 Resection D2 Surgery Following Preoperative Chemotherapy Postoperative Chemotherapy Intraperitoneal Therapy Treatment of Metastatic Disease and Palliation of the Incurable Patient Surgery (Figs. 72.4 and 72.5) Radiation Alone or Plus Chemotherapy Chemotherapy Three-Drug Regimens Second-Line Chemotherapy Targeted Therapies Immunotherapy Immune Checkpoints Anti–Programmed Death-1 Antibodies Key References References 73 Cancer of the Small Bowel Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy Adjuvant Therapy Locally Advanced Disease Palliation Treatment of Metastatic Disease Epidemiology Etiology and Biologic Characteristics Environmental Factors Genetic Factors Immunologic Conditions Diagnosis and Early Detection Clinical Manifestations Malignant Tumors of the Small Bowel Adenocarcinoma Crohn Disease Primary Therapy, Locally Advanced Disease, and Treatment of Metastatic Disease Neuroendocrine Tumors Carcinoid Syndrome Primary therapy, locally advanced disease, and treatment of metastatic disease Gastrointestinal Lymphoma Primary therapy, locally advanced disease, and treatment of metastatic disease. Gastrointestinal Sarcomas Primary Therapy, Locally Advanced Disease, and Treatment of Metastatic Disease Secondary Malignancies Benign Tumors of the Small Bowel Adenomas Leiomyomas Lipomas Desmoid Tumors Hemangiomas Hamartomas Surgical Considerations: Laparoscopic Versus Open Resection Summary Key References References 74 Colorectal Cancer Summary of Key Points Epidemiology Screening and Prevention of Colorectal Cancer Diagnosis and Staging Molecular Pathogenesis Surgical Treatment Surveillance Adjuvant Therapy in Early-Stage Colorectal Cancer Management of Metastatic Disease Epidemiology of Colorectal Cancer Incidence Mortality Risk Factors for Colorectal Cancer Inherited Colorectal Cancer Syndromes Lynch Syndrome (Formerly Hereditary Nonpolyposis Colon Cancer) Familial Adenomatous Polyposis MUTYH-Associated Polyposis (MAP) Hamartomatous Polyposis Syndromes Common Genetic Risk Factors Genome-Wide Association Studies and Colorectal Cancer Risk Family History of Colorectal Cancer or Adenomatous Polyps Prior Polyps and Inflammatory Bowel Disease Diabetes Mellitus and Obesity Alcohol Smoking Screening and Prevention of Colorectal Cancer Physical Activity Diet and Prevention of Colorectal Cancer The Role of Dietary Fiber Decreased Red Meat Consumption The Microbiome, Diet, and Cancer Prevention Strategies Calcium and vitamin D Folate supplementation Lifestyle Nonsteroidal Antiinflammatory Drugs, Hormone Replacement Therapy, and Statins Screening for Colorectal Cancer Screening Tests Fecal occult blood testing Fecal immunohistochemistry test Multitargeted stool DNA testing Flexible sigmoidoscopy Colonoscopy Computed tomography colonography Right-sided colon cancers Adoption of colorectal cancer screening Circulating tumor cells Cost-Effectiveness of Colorectal Cancer Screening Screening Options Diagnosis and Staging of Colorectal Cancer Diagnosis Laboratory Evaluation Staging Histopathology Pathologic Markers for Colorectal Cancer Imaging Modalities for Staging of Colon Cancer Computed tomography Magnetic resonance imaging Fluorodeoxyglucose–positron emission tomography Intraoperative ultrasonography (transcutaneous and laparoscopic) Molecular Pathogenesis (Molecular Basis of Colorectal Cancer) The Epidermal Growth Factor Receptor Pathway Chromosomal Instability Tumors APC–β-Catenin–Wnt Signaling Pathway KRAS, NRAS, and BRAF Defective Mismatch Repair Pathway Microsatellite Instability Tumors Detection of microsatellite instability tumors Clinical relevance of microsatellite instability Epigenetics and Colorectal Cancer Gene Expression Profiling and Colorectal Cancer Molecular Pathology: Translating the Molecular Understanding of Colorectal Cancer to Clinical Application Surgical Treatment Perioperative Clinical Management Enhanced Recovery Programs Mechanical Bowel Preparation Perioperative Nutrition and Fasting and Intraoperative Fluid Management Thromboembolism Prophylaxis Laparoscopic Surgery Prognostic Factors and Relationship to Mode of Surgical Resection Laparoscopic Colorectal Cancer Surgery Contraindications to Laparoscopic Surgery Surgical Resectional Approaches for Colorectal Cancer Restoring Bowel Continuity Surgical Management of Lymph Nodes in Colorectal Cancer Surgical Management of Obstructing Colorectal Cancer Surgical Management With Involvement of Adjacent Organs Surgical Management of Perforated Colorectal Cancer Surgical Management of the Malignant Colon Polyp Transanal Endoscopic Microsurgery for Rectal Cancer Surgical Management of Synchronous Metastatic Disease Surgical management of liver metastases Perioperative chemotherapy for liver metastases Radiofrequency Ablation Surgical management of the ovaries Managing Complications of Colorectal Cancer Surgery Managing Uncommon Colonic Tumors Surgical Management of Tumors of the Appendix Outcomes of Surgical Treatment and Role of Adjuvant Therapy Surveillance After Curative Resection Carcinoembryonic Antigen in the Management of Patients With Colorectal Cancer Evaluation of a Patient With Symptoms or Signs Evaluation of a Patient With Findings on Screening Evaluations Patients With Potentially Resectable Recurrent Disease Indications for Adjuvant Therapy Clinical and Molecular Risk Factors History of Development of Adjuvant Treatment and Established Adjuvant Regimens Adjuvant Treatment of Patients With Stage II Colon Cancer Adjuvant Treatment of Patients With Stage III Colon Cancer Adjuvant Oxaliplatin Combinations Adjuvant Irinotecan Combinations Adjuvant Chemotherapy and Toxicity Adjuvant Chemotherapy Combinations With Biological Agents Role of Adjuvant Radiation Therapy Choice of End Points in Adjuvant Therapy of Colorectal Cancer Medical Treatment of Metastatic Colorectal Cancer Evaluating Response to Treatment 5-Fluorouracil for the Treatment of Metastatic Colorectal Cancer Randomized Trials of 5-Fluorouracil Regimens Orally Available Fluoropyrimidines Combination of Fluoropyrimidines With Oxaliplatin and Irinotecan Oxaliplatin Complications of oxaliplatin-containing treatment regimens Irinotecan The Role of Biological Agents Antiangiogenic Approaches Bevacizumab Ramucirumab Aflibercept Cediranib Vatalanib Sunitinib Regorafenib TAS-102 (Trifluridine-Tipiracil) The Role of Epidermal Growth Factor Receptor–Targeted Therapies Monoclonal Antibodies Targeting Epidermal Growth Factor Receptor Cetuximab The Role of RAS in Response to Anti–Epidermal Growth Factor Receptor Therapies Panitumumab Anti-Epidermal Growth Factor Receptor–Targeted Therapies Versus Bevacizumab as First-Line Treatment of Metastatic Colorectal Cancer Epidermal Growth Factor Receptor–Targeted Tyrosine Kinase Inhibitors Gefitinib Erlotinib Immune Checkpoint Inhibitors Pembrolizumab Ipilimumab Combination Targeted Therapies Future Directions Acknowledgment Key References References 75 Cancer of the Rectum Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy Adjuvant Therapy Locally Advanced Disease Palliation Treatment of Metastatic Disease Epidemiology Etiology and Biologic Characteristics Chromosomal Instability Microsatellite Instability Hypermethylation of DNA Prevention and Early Detection Pathology and Pathways of Spread Pathology Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Clinical Manifestations Patient Evaluation Imaging Computed tomography Magnetic resonance imaging Endorectal ultrasound Positron emission tomography Staging Primary Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Controversies, Problems, and Challenges Watch and Wait Local Excision of T2 Tumors After Neoadjuvant Chemoradiotherapy Future Possibilities and Clinical Trials Key References References 76 Cancer of the Anal Canal Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Pathology and Tumor Biology Primary Therapy Prognosis Anatomy Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations and Patient Evaluation Staging Primary Therapy Squamous Cell Carcinoma Surgery Prospective Trials Evaluating Combined-Modality Therapy Role of Mitomycin C in Combined-Modality Therapy Replacing the 5-Fluorouracil Infusion With Capecitabine Time and Dose Considerations in Chemoradiotherapy for Anal Cancer Advances in Pelvic Radiotherapy Intensity-Modulated Radiation Therapy for Anal Cancer The Use of Intensity-Modulated Radiation Therapy in Reducing the Acute Toxicity of Chemoradiation Perianal Cancers and Nonsquamous Histologies of the Anal Canal Perianal skin (anal margin) tumors. Anal Canal Adenocarcinoma Anal Canal Melanomas Treatment of Metastatic Disease Controversies, Challenges, and Future Clinical Trials Key References References 77 Liver and Bile Duct Cancer Summary of Key Points Liver Cancer Biliary Tumors Liver Cancer Epidemiology Etiologic and Biologic Characteristics Viral Hepatitis Alcohol Metabolic Disorders Environmental Exposures Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Clinical Manifestations Patient Evaluation Staging Primary Treatment and Adjuvant Therapy Primary Therapy Resection Partial hepatectomy. Total hepatectomy and transplantation. Treatment complications. Follow-up program. Treatment of Recurrence Ablative therapies Adjuvant Therapy Locally Advanced Disease and Palliation Hepatic Artery Embolization Radiation Therapy Treatment of Metastatic Disease Chemotherapy Tyrosine Kinase Inhibitors Intraarterial Chemotherapy Immunotherapy Controversies, Problems, and Challenges Systemic Therapy in Patients With Advanced Cirrhosis Systemic Therapy and Etiology Immune checkpoint inhibitors CTLA-4 blockade. PD-1 and PD-L1 blockade. Novel checkpoint inhibitors, combinations strategies, and future directions. Oncolytic viruses Combined Local and Systemic Therapy Radiation therapy and sorafenib Embolization and immunotherapy Radioembolization and sorafenib Future Possibilities and Clinical Trials Gallbladder Cancer Epidemiology Etiologic and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Primary Treatment and Adjuvant Therapy Role of Staging Laparoscopy Extent of Resection Follow-Up Program Adjuvant Therapy Treatment of Metastatic Disease Chemotherapy Novel Therapeutics Immunotherapy Bile Duct Carcinoma Epidemiologic and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Hilar Cholangiocarcinoma Distal Extrahepatic Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Primary Treatment and Adjuvant Therapy Proximal (Hilar) Cholangiocarcinoma Distal Extrahepatic Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Follow-Up Program Adjuvant Therapy Chemotherapy Radiation therapy Treatment of Metastatic Disease Intraarterial Chemotherapy Locally Advanced Disease and Palliation Controversies, Problems, and Challenges Future Possibilities and Clinical Trials Key References References 78 Carcinoma of the Pancreas Summary of Key Points Epidemiology Risk Factors Etiologic and Biological Characteristics Molecular Biology Precursor Lesions Prevention and Early Detection Pathology and Pathways of Spread Pathology Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Signs and Symptoms Diagnosis Staging Primary Therapy Surgery Adjuvant Therapy Adjuvant Chemotherapy Adjuvant Chemoradiation Neoadjuvant Therapy Neoadjuvant Therapy for Borderline Resectable Disease Locally Advanced and Metastatic Disease Chemotherapy for Locally Advanced and Metastatic Disease First-line chemotherapy Gemcitabine-based regimens Gemcitabine-based combinations 5-fluoroacil–based regimen Second-line chemotherapy Recurrence after adjuvant chemotherapy Radiation for Locally Advanced Disease Palliative Therapy Controversies, Problems, Challenges, and Future Possibilities and Clinical Trials Key References References G Genitourinary 79 Cancer of the Kidney Summary of Key Points Epidemiology Risk Factors for Sporadic Renal Cell Adenocarcinoma Pathology Genetics and Biologic Characteristics of Renal Cell Carcinoma Sporadic Renal Cell Carcinoma Clear Cell Renal Cell Carcinoma Papillary Types I and II Renal Cell Carcinoma Chromophobe Renal Cell Carcinoma TFE3-Fusion Renal Cell Carcinoma Familial Renal Cell Carcinoma Diagnosis of Renal Cell Carcinoma Staging Systems for Renal Cell Carcinoma Prognostic Factors for Renal Cell Carcinoma Management Options for Localized Disease Radical Nephrectomy Nephron-Sparing Surgery Surgical Approach Thermal Ablation for Renal Cell Carcinoma Active Surveillance Surveillance After Treatment of Localized Renal Cell Carcinoma Sporadic renal cell carcinoma von Hippel-Lindau disease and other familial renal cell carcinomas Neoadjuvant and Adjuvant Medical Therapies Neoadjuvant Therapy Prior to Debulking Nephrectomy Adjuvant Therapy Cytoreductive Nephrectomy for Patients With Metastatic Renal Cell Carcinoma Resection of Metastases in Renal Cell Carcinoma Food and Drug Administration–Approved Therapies for Advanced Disease Immunotherapy High-Dose Interleukin-2 Checkpoint Inhibitors Angiogenesis Inhibitors Sorafenib Sunitinib Bevacizumab and Interferon Pazopanib Axitinib Cabozantinib Lenvatinib and Everolimus Inhibitors of the Mammalian Target of Rapamycin Pathway Temsirolimus Everolimus Future Directions for Antiangiogenesis Therapies Future Potential Strategies for Renal Cell Carcinoma Treatment of Kidney Cancers With Nonconventional Histologic Features Summary Key References References 80 Carcinoma of the Bladder Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy Neoadjuvant and Adjuvant Therapy Advanced Disease Epidemiology Etiologic and Biologic Characteristics Etiology Molecular Biology Prevention and Early Detection Pathology and Natural History Staging Classification Clinical Manifestations Patient Evaluation Primary Therapy Transurethral Resection of Bladder Tumor Treatment for Non–Muscle-Invasive Disease Intravesical Bacillus Calmette-Guérin Intravesical Therapy With Chemotherapeutic Agents Surveillance After Intravesical Therapy Treatment for Muscle-Invasive Localized Disease Radical Cystectomy Urinary Diversion Cutaneous incontinent urinary diversion Cutaneous continent urinary diversion Orthotopic Neobladder Preoperative or Postoperative Chemotherapy Adjuvant Chemotherapy Neoadjuvant Chemotherapy Preoperative or Postoperative Radiation Therapy Partial Cystectomy Trimodality Bladder Preservation Therapy Effective Radiosensitizing Chemotherapy Agents Morbidity, Bladder Function, and Quality of Life After Trimodality Bladder Preservation Therapy Ideal Candidates for Trimodality Bladder Preservation Therapy Salvage Cystectomy After Trimodality Bladder Preservation Therapy Treatment for Locally Advanced and Metastatic Disease Systemic Therapy Radiation Therapy Key References References 81 Prostate Cancer Summary of Key Points Incidence Biologic Characteristics Screening, Diagnosis, and Staging Primary Therapy Adjuvant Therapy Treatment of Advanced Disease Prostate Anatomy and Function Genetics and Epidemiology Genetic Predisposition to Prostate Cancer Epidemiology of Prostate Cancer Prostate Inflammation and Prostate Cancer Etiologic and Biologic Characteristics Somatic Genome Alterations in Prostate Cancer Cells Changes in Gene Expression in Prostate Cancers Telomere Shortening During Prostatic Carcinogenesis Pathology and Pathways of Spread Histopathology of Prostate Cancer Life-Threatening Prostate Cancer Progression Prostate Cancer Screening, Early Detection, and Prevention Clinical Evaluation Digital Rectal Examination Serum Prostate-Specific Antigen Serum Prostate-Specific Antigen and Prostate Cancer Detection Prostate Specific Antigen–Based Screening for Prostate Cancer Prostate Biopsy Prostate Cancer Prevention Clinical Manifestations, Patient Evaluation, and Staging Evaluation of the Extent of Prostate Cancer Radiographic Imaging for Prostate Cancer Staging “Molecular” Assays for Prognosis Primary Therapy Selection of Treatment Approach Observational Strategies Radical Prostatectomy Urinary Function After Radical Prostatectomy Erectile Function After Radical Prostatectomy Control of Prostate Cancer With Radical Prostatectomy Radiation Therapy External Beam Radiotherapy for Localized Prostate Cancer Using Three-Dimensional–Conformal and Intensity-Modulated Approaches Complications of three-dimensional–conformal and intensity-modulated radiation therapy Cancer control with external beam radiation therapy Brachytherapy Toxicity of brachytherapy Proton Beam Radiotherapy Adjuvant Endocrine Therapy Postprostatectomy Adjuvant Radiation Therapy Salvage Radiotherapy After Radical Prostatectomy Locally Advanced Disease and Palliation Radiation Therapy and Adjuvant Endocrine Therapy for Locally Advanced Prostate Cancer Treatment of Metastatic Disease Natural History of Metastatic Prostate Cancer Treatments Targeting Androgen Signaling Androgen Deprivation Therapy Antiandrogens and “Complete” Androgen Blockade Inhibitors of Adrenal Steroidogenesis Optimal Timing of Androgen Deprivation Therapy Cytotoxic Chemotherapy for Metastatic Castration-Resistant Prostate Cancer Docetaxel Cabazitaxel Chemohormonal Therapy for Metastatic Hormone-Sensitive Prostate Cancer AR-V7 as a Treatment-Selection Biomarker in Castration-Resistant Prostate Cancer Immunotherapy With Sipuleucel-T Bone-Targeted Treatments Zoledronic Acid Denosumab Strontium-89, Samarium-153, and Radium-223 Poly (ADP-Ribose) Polymerase Inhibitors Summary (Fig. 81.18) Key References References 82 Cancer of the Penis Summary of Key Points Incidence Biologic Characteristics Primary Therapy Adjuvant Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Epidemiology Etiology and Biologic Characteristics Prevention and Early Detection Pathology and Pathways of Spread Leukoplakia Penile Lichen Sclerosus (et Atrophicus) Carcinoma in Situ or Penile Intraepithelial Neoplasia Bowenoid Papulosis Buschke-Löwenstein Tumor (Verrucous Carcinoma) Nonsquamous Malignancy Metastatic Tumors Primary Squamous Cell Carcinoma Clinical Manifestations, Patient Evaluation, and Staging Primary Therapy Penile Sparing Management of Penile Cancer Management of Locally Advanced Disease Treatment of Associated Inguinal Lymphadenopathy Radiation Therapy Multimodal Therapy Locally Advanced Disease and Palliation Treatment of Metastatic Disease Single-Agent Chemotherapy Combination Chemotherapy Cisplatin and 5-Fluorouracil Cisplatin, Bleomycin, and Methotrexate Vincristine, Bleomycin, and Methotrexate Cisplatin, 5-Fluorouracil, and Taxane Controversies, Problems, Challenges, Future Possibilities, and Clinical Trials Key References References 83 Testicular Cancer Summary of Key Points Incidence Differential Diagnosis Diagnosis and Staging Evaluation Primary Therapy Effective Second- and Third-Line Therapies Epidemiology Incidence Etiology Molecular Biology Histology and Natural History Overview of Histology Overview of Natural History Seminoma Embryonal Carcinoma Teratoma and Teratocarcinoma Choriocarcinoma Yolk Sac Tumors Stromal Cell Tumors Secondary (Metastatic) Neoplasms Clinical Manifestations Evaluation of the Patient: Diagnosis, Clinical Staging, and Risk Assessment Diagnosis: Testicular Ultrasonography Diagnosis: Orchiectomy Clinical Staging and Risk Assessment Tumor Markers Radiologic Evaluation Staging Management of Low-Stage Disease Clinical Stage I Seminoma Risk Assessment Treatment Clinical Stage I Nonseminoma Risk Assessment Treatment Retroperitoneal lymph node dissection Alternatives to retroperitoneal lymph node dissection Adjuvant radiation therapy. Adjuvant chemotherapy. Surveillance. Stage II Seminoma: Treatment and Results Stage II Nonseminoma Risk Assessment Treatment of Clinical Stage II Patients Retroperitoneal lymph node dissection followed by adjuvant chemotherapy Primary chemotherapy Management of Advanced Disease Risk Assessment Treatment of Good-Risk Advanced Germ Cell Tumors Poor-Risk Advanced Germ Cell Tumors Results of Clinical Trials in Poor-Prognosis Patients Addition of non–cross-resistant agents Dose escalation Unique High-Risk Germ Cell Tumors: Brain Metastases and Extragonadal Disease Extragonadal Germ Cell Tumors Brain Metastases Risk Assessment of Residual Masses After Chemotherapy: the Need for Adjunctive Surgery Residual Masses in Seminoma Residual Masses in Nonseminoma Growing Teratoma Syndrome Second-Line and Salvage Therapy Chemotherapy High-Dose Chemotherapy Surgery Third-Line and Post–High-Dose Chemotherapy Salvage Systemic Therapy Risk Assessment in Patients With Relapsed or Refractory Germ Cell Tumor Late Consequences Germ Cell Tumor Relapse Contralateral Testicular Cancer Early Detection of Recurrent Germ Cell Tumor Toxicity Acute Toxicities Chronic Toxicities of Radiation Therapy Chronic Toxicities of Chemotherapy Secondary Malignancies Key References References H Gynecological 84 Cancers of the Cervix, Vulva, and Vagina Summary of Key Points Cervical Cancer Vulvar Cancer Cancer of the Vagina Cervical Cancer Epidemiology Human Papillomavirus Biology Pathology Squamous Cell Carcinomas of the Cervix Cervical Adenocarcinomas Adenosquamous Carcinomas Neuroendocrine Tumors of the Cervix Clinical Presentation Screening Diagnosis Colposcopy Endocervical Curettage or Endocervical Brush Excisional Biopsy Loop Electrodiathermy Excision Procedure Diagnostic or Therapeutic Excisional Conization (Cone Biopsy) Patient Evaluation in Patients With Invasive Disease Staging Diagnostic Imaging Evaluation of Cervical Cancer Laboratory Evaluation Prognostic Factors Treatment Superficial Ablative Therapy Hysterectomy Extrafascial or simple hysterectomy (type I) Modified radical hysterectomy (type II) Radical hysterectomy (type III) Extended radical hysterectomy (type IV) Partial exenteration (type V) Surgical alternatives to conventional radical abdominal hysterectomy Sentinel Lymph Nodes Radiation Therapy Chemoradiation Treatment of Locoregional Disease by Stage Stages IA1 and IA2 (microinvasion) and small IB1 Stages IB1, IB2, and IIA Stages IIB and III Stage IVA Regional Disease Recurrent Disease Treatment of Metastatic Disease and Salvage Chemotherapy Vulvar Cancer Epidemiology Etiology Natural History Vulvar Dystrophy Paget Disease Intraepithelial Squamous Cell Neoplasia of the Vulva Invasive Squamous Cell Carcinoma of the Vulva Clinical features Routes of spread Staging Diagnosis Treatment Treatment of Preinvasive Disease Surgical Treatment of Invasive Carcinoma Surgical Techniques Radical local excision Radical vulvectomy Groin lymph node dissection Radiation Therapy Adjuvant postoperative radiation therapy Preoperative chemoradiation Radical radiation and chemoradiation Elective groin radiation Radiation techniques, volumes, and doses Chemotherapy Chemotherapy or radiation therapy for recurrent, persistent, or metastatic vulvar carcinoma Other Histologic Types Adenosquamous Carcinoma Melanoma Staging Treatment Prognosis Basal Cell Carcinoma Bartholin Gland Carcinoma Sarcoma Verrucous Carcinoma Cancer of the Vagina Epidemiology Etiology Patterns of Spread Signs and Symptoms Diagnosis Staging Treatment Surgery Radiation Therapy Intervention by Stage Stage I disease Stage II or III disease Stage IVA disease Patients With a Central Recurrence After Previous Surgery or Radiation Therapy Complications of Therapy Prognosis Adenocarcinoma Sarcomas Endodermal Sinus Tumors Melanoma Chemotherapy for Persistent, Recurrent, or Metastatic Vaginal Cancer Key References References 85 Uterine Cancer Summary of Key Points Incidence Biological Characteristics Staging Evaluation Primary Therapy and Results Adjuvant Therapy Locally Advanced, Metastatic, or Recurrent Disease Prognosis Epidemiology Etiology and Biological Characteristics Genetics Risk Factors Previous Irradiation Other Comorbidities Protective Factors Prevention and Early Detection Pathology and Pathways of Spread Pathogenesis Overview Endometrial Hyperplasia Endometrioid Adenocarcinoma Uterine Serous Carcinoma Clear Cell Carcinoma Carcinosarcoma Sarcoma Leiomyosarcoma Endometrial Stromal Sarcoma Undifferentiated Stromal Sarcomas Mixed Epithelial–Nonepithelial Tumors Molecular Pathways Clinical Features Staging Prognosis With Risk Factors Stage Depth of Invasion Grade Histologic Subtype Therapy Surgery as a Single Modality Role of Lymphadenectomy Adjuvant Treatment of Low- and Intermediate-Risk Endometrial Cancer Adjuvant Treatment of High-Risk Endometrial Cancer Uterine Serous Carcinoma Clear Cell Carcinoma Uterine Carcinosarcomas Advanced-Stage Endometrial Cancer Treatment of Uterine Sarcomas Radiation for Inoperable Patients Treatment of Advanced Endometrial Cancer Treatment of Recurrent Disease and Palliation Endocrine Therapy Novel Targeted Therapies Fertility-Sparing Treatment Future Directions Key References References 86 Carcinoma of the Ovaries and Fallopian Tubes Summary of Key Points Epidemiology Incidence Mortality Rate Risk Factors Genetics, Prevention, and Early Detection Inherited Genetic Risk Prevention Early Detection Pathology Clinical Symptoms Diagnostic Tools Staging and Surgery Neoadjuvant Chemotherapy Before Surgery Surgery for Recurrence Chemotherapy (Upfront) Alterations in Frontline Treatment Strategies Neoadjuvant Chemotherapy Interval Cytoreduction Additions to the Paclitaxel and Carboplatin Backbone Intraperitoneal Therapy Dose-Dense Chemotherapy Maintenance Therapy Chemotherapy (Relapsed Disease) Platinum-Refractory Disease Platinum-Resistant Disease Platinum-Sensitive Disease Novel Agents Poly-ADP-Ribose Polymerase Pathway P53 Antiangiogenesis Therapy Immune Therapy Key References References 87 Gestational Trophoblastic Disease Summary of Key Points Incidence and Epidemiology Pathology Clinical Features Staging and Classification Primary Therapy Complications Prognosis Introduction Terminology Relevant Historical Issues Incidence and Epidemiology Etiology and Pathogenesis Pathology Complete Hydatidiform Mole Partial Hydatidiform Mole Invasive Mole Choriocarcinoma Placental Site and Epithelioid Trophoblastic Tumors Immunobiology Clinical Presentation Complete Molar Pregnancy Partial Molar Pregnancy Gestational Trophoblastic Neoplasia Nonmetastatic Gestational Trophoblastic Neoplasia Metastatic Gestational Trophoblastic Neoplasia Pulmonary metastasis Vaginal metastases Hepatic metastases Brain metastases Other metastatic sites Placental site and epithelioid trophoblastic tumors Laboratory and Imaging Studies Human Chorionic Gonadotropin Measurement False-Positive Human Chorionic Gonadotropin Test Results Quiescent Gestational Trophoblastic Disease Ultrasound Computed Tomography and Magnetic Resonance Imaging Positron Emission Tomography Staging and Prognostic Scoring System Treatment (Fig. 87.8) Molar Pregnancy Surgical Management Role of Prophylactic Chemotherapy Persistent Gestational Trophoblastic Neoplasia Diagnosis Chemotherapeutic Agents Single-agent chemotherapy Methotrexate with folinic acid rescue 5-Fluorouracil. Actinomycin D. Etoposide. Multiagent chemotherapy EMACO and EMAEP. Vinblastine, bleomycin, and cisplatin. 5-Fluorouracil and floxuridine. Other multiagent regimens Method of administration Treatment Protocols and Results Stage I Stages II and III Management of vaginal and adnexal metastases Management of lung metastases Stage IV Management of cerebral metastases Management of hepatic metastases Management of Relapsed and Chemoresistant Gestational Trophoblastic Neoplasia Management of Placental Site Trophoblastic Tumor and Epithelioid Trophoblastic Tumor Follow-Up After Evacuation of a Molar Pregnancy After Treatment for Gestational Trophoblastic Neoplasia Stages I to IV Subsequent Pregnancy After Complete Hydatidiform Mole After Partial Hydatidiform Mole Recurrent Molar Pregnancy After Gestational Trophoblastic Neoplasia Psychosocial Consequences of Gestational Trophoblastic Neoplasia Issues for the Future Key References References 88 Cancer of the Breast Summary of Key Points Incidence and Epidemiology Biology and Estimation of Risk Screening and Diagnosis Management of Noninvasive Disease Management of Early-Stage Breast Cancer Management of Locally Recurrent Disease Management of Metastatic Disease Epidemiology Incidence Diet Ionizing Radiation Exogenous Hormones Reproductive Factors and Endogenous Hormones Obesity and Body Habitus Prior Breast Biopsy Familial History and Predictive Models of Breast Cancer Risk BRCA1, BRCA2, TP53, and Hereditary Susceptibility to Breast Cancer Biologic Characteristics and Pathology Histology Invasive Breast Carcinoma BRCA-Associated Breast Cancers Noninvasive Breast Carcinomas Estrogen and Progesterone Receptors ERBB2 (HER2) PI3K and PTEN TP53 Breast Cancer Genome Molecular Profiling in Breast Cancer Comprehensive Genomic Analysis Breast Cancer Stem Cells Breast Cancer Detection in the Circulation Disseminated Tumor Cells Liquid Biopsies Prevention and Early Detection Increased Surveillance Behavior Modification Chemoprevention Prophylactic Mastectomy and/or Oophorectomy Clinical Manifestations and Patient Evaluation Detection of Breast Cancer Screening and Early Detection Screening guidelines Risks of screening Mammography Digital breast tomosynthesis Other methods of screening Breast magnetic resonance imaging. Ultrasonography. Screening the elderly patient Mammographic Abnormalities Masses Calcifications Architectural Distortion Approach to the Patient Management of the Palpable Mass Management of the Nonpalpable Mammographic Abnormality Staging Seventh Edition of the TNM Staging System Prognostic and Predictive Factors for Invasive Carcinoma Primary Therapy Management of Noninvasive Breast Cancer Lobular Carcinoma in Situ Ductal Carcinoma in Situ Treatment of ductal carcinoma in situ Management of Early-Stage Invasive Breast Cancer Surgery for Early-Stage Breast Cancer Resection of the Primary Tumor Mastectomy Contralateral Prophylactic Mastectomy Management of the Axilla Irradiation of the Intact Breast Complications of Treatment Adjuvant Postmastectomy Irradiation Adjuvant Systemic Therapy Adjuvant Chemotherapy Who Should Receive Chemotherapy? Chemotherapy Regimens Adjuvant Therapy for Triple-Negative Breast Cancer Adjuvant Anti-HER2 Therapy Preoperative Systemic Therapy Adjuvant Endocrine Therapy Tamoxifen Ovarian function suppression Aromatase inhibitors Schedule and duration of adjuvant endocrine therapy Combined chemoendocrine therapy Preoperative endocrine therapy Secondary Effects of Adjuvant Systemic Therapy Secondary effects of chemotherapy Secondary effects of endocrine therapy Long-Term Follow-Up New Strategies in Adjuvant Treatment Recurrence After Breast Conservation Therapy Management of Metastatic Disease Evaluation of Suspected Metastases Endocrine Therapy Selective Estrogen Receptor Modulators Aromatase Inhibitors Ovarian Ablation Other Antiestrogens Combination Regimens With Antiestrogens for Postmenopausal Patients Chemotherapy Single-Agent Chemotherapy Combination Chemotherapy HER2-Targeted Therapy Therapies Targeting Angiogenesis Bisphosphonates Unusual Problems Encountered in Breast Cancer Inflammatory Disease Male Breast Cancer Breast Cancer and Pregnancy Breast Cancer During Pregnancy Pregnancy After Breast Cancer Axillary Metastases With Occult Breast Cancer Paget Disease of the Breast Phyllodes Tumors of the Breast Future Strategies Key References References I Sarcomas 89 Sarcomas of Bone Summary of Key Points Incidence and Epidemiology Diagnosis and Radiographic Staging Prognostic Factors Staging System Primary Therapy Future Trends Staging Surgical Staging System Radiographic Staging Staging Biopsy Osteosarcoma Epidemiology Etiologic and Biologic Considerations p53-ARF-MDM2 Pathway CIP/KIP Family of Cyclin-Dependent Kinase Inhibitors Other Important Players Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Primary Therapy Adjuvant Chemotherapy Relationship of Surgical Margins, Neoadjuvant Chemotherapy, and Local Recurrence Surgical Treatment Rotationplasty Resection and Distraction Osteogenesis Expandable Prostheses Amputation Surgical Options for Limb Salvage Reconstruction Endoprostheses Bone allografts Local Recurrence Management of Patients With High-Grade Osteosarcoma and Pathologic Fractures Treatment of Metastatic Disease Controversies, Problems, Challenges, and Late Effects of Therapy Metachronous Osteosarcoma Second Malignant Neoplasms Osteosarcoma Variants High-Grade Variants High-grade surface osteosarcoma Primary therapy. Controversies, challenges, and future possibilities. Extraskeletal osteosarcoma Epidemiology. Clinical manifestations. Primary therapy. Pagetoid osteosarcoma Epidemiology. Clinical manifestations. Postradiation osteosarcoma of bone Epidemiology. Clinical manifestations. Primary therapy. Small cell osteosarcoma Clinical manifestations. Primary therapy. Osteosarcoma after age 40 years Low-Grade Variants Low-grade central osteosarcoma Epidemiology. Clinical manifestations. Primary therapy. Periosteal osteosarcoma Clinical manifestations. Primary therapy. Parosteal osteosarcoma Epidemiology. Clinical manifestations. Primary therapy. Chondrosarcoma Epidemiology Etiologic and Biologic Characteristics Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Primary Therapy Locally Recurrent Disease, Metastatic Disease, and Palliation Ewing Sarcoma Epidemiology Etiologic and Biologic Characteristics Pathology and Pathways of Spread Clinical Manifestations, Patient Evaluation, and Staging Radiographic Features Prognosis Primary Therapy Chemotherapy Local Control Current Guidelines for Surgical Therapy Amputation Treatment of Local Recurrence Treatment of Metastatic Disease Late Effects of Treatment Functional Results Secondary Malignancies Future Possibilities and Clinical Trials Malignant Fibrous Histiocytoma of Bone Epidemiology Clinical Manifestations Primary Therapy Adamantinoma of Bone Primary Sarcomas of the Spine Clinical Manifestations, Patient Evaluation, and Staging Primary Malignant Tumors of the Spine Osteosarcoma of the Spine Chondrosarcoma of the Spine Primary Ewing Sarcoma of the Spine Chordoma Cervical and Sacrococcygeal Chordoma Epidemiology Clinical Manifestations, Patient Evaluation, and Staging Vertebral Chordoma Primary Treatment Sacrococcygeal Chordoma Primary therapy Future Possibilities Key References Epidemiology Staging Osteosarcoma: chemotherapy Surgery Local recurrence Metastatic disease Chondrosarcoma Ewing sarcoma Primary sarcomas of the spine Chordoma References 90 Sarcomas of Soft Tissue Summary of Key Points Incidence and Epidemiology Diagnosis and Evaluation of Extent of Disease Prognostic Factors Staging Systems Primary Therapy Recurrent Disease Etiology and Epidemiology Environmental Factors Genetic Predisposition Genetics of Sporadic Soft Tissue Sarcomas Chromosomal Rearrangements Sarcomas With Complex Karyotypes Pathology Classification Histologic Grading Clinical Presentation and Diagnosis Biopsy Imaging Staging Prognostic Factors Conventional Clinicopathologic Factors Potential Molecular Prognostic Factors Prognostic Factors as Therapeutic Targets Molecular Therapeutic Targets in Sarcomas: Gastrointestinal Stromal Tumor Treatment of Localized Primary Soft Tissue Sarcoma Surgery Limb-Sparing Surgery Versus Amputation Completeness of Resection Lymph Node Dissection Surgery Alone Preoperative or Postoperative Radiotherapy Local Control Relationship Between Local Control and Survival Treatment Sequencing: Preoperative Versus Postoperative Treatment Conformal Radiotherapy and Intensity-Modulated Radiotherapy Conventional Radiotherapy Without Surgery Particle-Based Radiotherapy (Emphasizing Proton Beam Therapy) Chemotherapy Adjuvant Chemotherapy Neoadjuvant Chemotherapy Combined Preoperative Chemotherapy and Radiotherapy Hyperthermic Isolated Limb Perfusion and Whole-Body Hyperthermia With Chemotherapy Treatment of Sarcoma Patients at Specialty Centers Treatment of Locally Recurrent Soft Tissue Sarcoma Incidence of Local Recurrence Surgery and Radiotherapy Treatment of Metastatic Soft Tissue Sarcoma Surgical Resection Chemotherapy First-Line Chemotherapy Single agents Combination chemotherapy Second-Line Chemotherapy High-dose ifosfamide Other marketed drugs alone or in combination Newer drugs Unique routes of delivery Special Sites and Subtypes of Sarcoma Retroperitoneal Sarcomas Surgery Plus Radiation Treatment Intraoperative Radiation Treatment Chemotherapy Gastrointestinal Stromal Tumors Localized (Surgically Resectable) Gastrointestinal Stromal Tumors Metastatic Gastrointestinal Stromal Tumors Chemotherapy Surgery Head and Neck Sarcomas Radiation Treatment Genitourinary Sarcomas Uterine Sarcomas and Carcinosarcomas Chemotherapy Desmoid Tumors (Aggressive Fibromatoses) Surgery and Radiation Chemotherapy Breast Sarcomas Vascular Sarcomas Surgery Adjuvant Therapy Chemotherapy Considerations for Specific Histologic Subtypes Synovial sarcomas Leiomyosarcomas Liposarcomas Pediatric Sarcomas in Adults Key References References J Cancer of Undefined Site of Origin 91 Carcinoma of Unknown Primary Summary of Key Points Incidence Evaluation Therapy Etiology and Epidemiology Biological Considerations Patient Evaluation History and Physical Examination Serum Tumor Markers Pathologic Evaluation General Considerations Light Microscopy Immunohistochemistry Overview of Imaging Studies Mammography Computed Tomography Magnetic Resonance Imaging Positron Emission Tomography Carcinoma of Unknown Primary and Tissue-of-Origin Gene Profiling Studies Carcinoma of Unknown Primary and Next-Generation Sequencing Treatment Decisions and Emerging Subsets General Considerations Favorable Clinical Subsets Squamous Carcinoma Involving Mid-High Cervical Lymph Nodes Women With Isolated Axillary Adenopathy Women With Serous Papillary Peritoneal Carcinomatosis Poorly Differentiated and Undifferentiated Carcinoma (Extragonadal Germ Cell Cancers) Poorly Differentiated Neuroendocrine Carcinoma Solitary Metastases Colon Cancer Profile With Unknown Primary Carcinoma of Unknown Primary in Unselected Patients Changing Status of Therapeutics for Carcinoma of Unknown Primary Future Directions References K Pediatrics 92 Pediatric Solid Tumors Summary of Key Points Osteosarcoma Ewing Sarcoma Family Tumors Neuroblastoma Wilms Tumor Renal Cell Carcinoma Rhabdomyosarcoma Nonrhabdomyosarcoma Soft Tissue Sarcoma Retinoblastoma Hepatoblastoma Adrenocortical Carcinoma Osteosarcoma Epidemiology Tumor Biology Pathology Clinical Manifestations Laboratory and Radiologic Evaluation Osteosarcoma Subtypes Telangiectatic Osteosarcoma Low-Grade Intramedullary Osteosarcoma Surface Osteosarcomas Prognostic Factors Treatment Ewing Sarcoma Family Tumors Epidemiology Tumor Biology Pathology Clinical Manifestations Laboratory and Radiologic Evaluation Prognostic Factors Treatment Neuroblastoma Epidemiology Tumor Biology Pathology Clinical Manifestations Laboratory and Radiologic Evaluation Prognostic Factors Treatment Wilms Tumor Epidemiology Tumor Biology Pathology Clinical Manifestations and Patterns of Spread Laboratory and Radiologic Evaluation Treatment Bilateral Wilms Tumor Recurrent Wilms Tumor Late Effects of Therapy Renal Cell Carcinoma Rhabdomyosarcoma Epidemiology Biology Pathology Clinical Manifestations Diagnostic Evaluation Prognostic Factors Treatment Outcome and Late Sequelae Nonrhabdomyosarcoma Soft Tissue Sarcoma Epidemiology Tumor Biology Clinical Manifestations Diagnostic Evaluation Prognostic Factors Treatment Outcome Retinoblastoma Epidemiology Clinical Forms and Tumor Biology Prevention, Early Detection, and Genetic Counseling Pathology Clinical Manifestations Evaluation Staging Principles of Treatment Surgery Focal Therapies Chemotherapy Radiotherapy Treatment of Intraocular Retinoblastoma Unilateral retinoblastoma Bilateral retinoblastoma Intravitreal and Intraarterial Chemotherapy for Intraocular Retinoblastoma Treatment of Extraocular Retinoblastoma Long-Term Effects of Retinoblastoma and Its Treatment Hepatoblastoma Epidemiology Tumor Biology Pathology Clinical Manifestations and Patterns of Spread Laboratory and Radiologic Evaluation Staging and Risk Stratification Treatment Adrenocortical Carcinoma Epidemiology Clinical Manifestations Diagnosis Prognostic Factors Treatment Nasopharyngeal Carcinoma Key References Osteosarcoma Ewing sarcoma family of tumors Neuroblastoma Wilms tumor Renal cell carcinoma Rhabdomyosarcoma Non-rhabdomyosarcoma soft tissue sarcoma Retinoblastoma Hepatoblastoma Adrenocortical carcinoma Nasopharyngeal carcinoma References Osteosarcoma Ewing sarcoma family of tumors Neuroblastoma Wilms tumor Renal cell carcinoma Rhabdomyosarcoma Non-rhabdomyosarcoma soft-tissue sarcoma Retinoblastoma Hepatoblastoma Adrenocortical carcinoma Nasopharyngeal carcinoma 93 Childhood Leukemia Summary of Key Points Incidence Etiology Epidemiology Clinical Findings Differential Diagnosis Therapy Prognosis Introduction Epidemiology Etiology Pathogenesis General Clinical and Laboratory Features Differential Diagnosis Morphologic and Cytochemical Analysis Immunologic Classification of Acute Leukemia Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Acute Leukemia of Ambiguous Lineage Genetic Alterations: B-Lineage Acute Lymphoblastic Leukemia Genetic Alterations: T-ALL Genetic Alterations: Acute Myeloid Leukemia Genetic Alterations: Myelodysplastic Syndrome, Juvenile Myelomonocytic Leukemia, and Chronic Myelogenous Leukemia Prognostic Factors and Treatment: Newly Diagnosed Acute Lymphoblastic Leukemia Prognostic Factors and Treatment: Relapsed Acute Lymphoblastic Leukemia Prognostic Factors and Treatment: Newly Diagnosed Acute Myeloid Leukemia Prognostic Factors and Treatment: Relapsed Acute Myeloid Leukemia Prognostic Factors and Treatment: Myelodysplastic Syndrome and Juvenile Myelomonocytic Leukemia Prognostic Factors and Treatment: Chronic Myelogenous Leukemia Short and Long-Term Complications of Therapy: Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia Issues for the Future Acknowledgements Key References References 94 Childhood Lymphoma Summary of Key Points Incidence Etiology and Epidemiology Pathology and Biology Clinical Findings Diagnosis and Differential Diagnosis Initial Workup and Staging Primary Therapy Salvage Therapy Complications Prognosis Introduction Epidemiology and Pathogenesis Pathology and Biology Burkitt Lymphoma Lymphoblastic Lymphoma Anaplastic Large-Cell Lymphoma Diffuse Large B-Cell Lymphoma Primary Mediastinal (Thymic) Large B-Cell Lymphoma Uncommon Pediatric Lymphomas Pediatric Follicular Lymphoma Pediatric Nodal Marginal Zone Lymphoma Clinical Presentation Diagnosis and Differential Diagnosis Initial Evaluation and Staging Workup Prognostic Factors Primary Treatment Initial Management Limited-Stage Disease Advanced-Stage Disease Burkitt lymphoma Lymphoblastic lymphoma Large-cell lymphoma Diffuse large B-cell lymphoma Anaplastic large-cell lymphoma. Rare histologic subtypes Central Nervous System Prophylaxis and Treatment Response Evaluation Emergency Situations Treatment Complications Follow-Up Management of Primary Treatment Failure After Completion of Therapy Clinic Future Directions Disclosure Key References References L Hematological 95 Acute Leukemias in Adults Summary of Key Points Incidence Biological Characteristics Diagnosis and Classification Treatment Introduction Epidemiology Etiology Genetic Predisposition Viruses Radiation Environmental Carcinogens Prior Therapy Antecedent Hematologic Malignancies Pathobiology Clonality The Leukemic Stem Cell Marrow Failure Morphology Immunophenotyping Cytogenetics and Mutational Analyses Cytogenetics and Mutational Analysis of Acute Myeloid Leukemia Cytogenetics of Acute Myeloid Leukemia Mutational Analysis of Acute Myeloid Leukemia Cytogenetic and Mutational Analysis of Acute Lymphocytic Leukemia Mutational Analysis of Acute Lymphocytic Leukemia Gene and MicroRNA Expression Classification of Acute Leukemia Clinical Manifestations Laboratory Manifestations Pretreatment Evaluation Therapy (Table 95.7) Preparing the Patient for Treatment Acute Myeloid Leukemia Remission Induction Response Criteria Measurement of Residual Disease Postremission Chemotherapy Allogeneic Hematopoietic Cell Transplantation Autologous Hematopoietic Cell Transplantation Treatment of Recurrent AML Treatment of Acute Myeloid Leukemia in Patients Not Candidates for Intensive Therapy Treatment of Acute Promyelocytic Leukemia Acute Lymphocytic Leukemia Remission Induction Postremission Therapy Measurement of Residual Disease in Acute Lymphocytic Leukemia Hematopoietic Cell Transplantation Treatment of Recurrent Acute Lymphocytic Leukemia Mature B-ALL Philadelphia Chromosome–Positive Acute Lymphocytic Leukemia Future Possibilities Whole-Genome Sequencing Measurable Residual Disease Immunotherapy Hematopoietic Cell Transplantation References 96 Myelodysplastic Syndromes Summary of Key Points Etiology Epidemiology Pathology Incidence Differential Diagnosis Prognosis Primary Therapy Second or Third Line Therapies History and Terminology Epidemiology and Etiology Environmental and Occupational Exposures Familial Myelodysplastic Syndromes Therapy-Related Myelodysplastic Syndromes Stem Cell Transplantation and Granulocyte Colony-Stimulating Factor Contributing to Myelodysplastic Syndromes Pediatric Myelodysplastic Syndromes Pathogenesis and Biology Stem Cell Origin and Microenvironment Expression Profiling and Point Mutations Immune Dysfunction Clinical Presentation Laboratory Evaluation and Pathologic Features Disease Classification French-American-British (FAB) Classification World Health Organization Classifications Prognosis International Prognostic Scoring System Criticisms of the International Prognostic Scoring System World Health Organization Classification-Based Prognostic Scoring System and MD Anderson Prognostic Scoring System Revised International Prognostic Scoring System Therapy Supportive Care: Transfusions and Hematopoietic Growth Factors Iron Chelation Immunosuppressive Therapy Immunomodulatory Therapy DNA Hypomethylating Agents Stem Cell Transplantation Developmental Therapeutics in Myelodysplastic Syndromes Summary of Therapeutic Recommendations (Fig. 96.9; see Table 96.14) Acknowledgments Key References References Self-Assessment Review Questions Answers 97 Myeloproliferative Neoplasms Summary of Key Points Incidence Differential Diagnosis Diagnostic Evaluation Risk Stratification Treatment Polycythemia Vera Pathogenesis Diagnosis Treatment Role of Drug Therapy in Polycythemia Vera Observations from randomized studies Observations from nonrandomized studies Thrombohemorrhagic Risk Factors in Polycythemia Vera Current Treatment Recommendations Treatment of Non–Life-Threatening Complications in Polycythemia Vera Essential Thrombocythemia Pathogenesis Diagnosis Treatment Antiplatelet Therapy in Essential Thrombocythemia Cytoreductive Therapy in Essential Thrombocythemia Pregnancy and Essential Thrombocythemia Primary Myelofibrosis Pathogenesis Diagnosis Treatment Prognostic Factors Hematopoietic Stem Cell Transplantation Conventional Drug Treatment of Anemia Management of Splenomegaly and Other Extramedullary Hematopoiesis Investigational Treatment Conclusion Key References References 98 Chronic Myeloid Leukemia Summary of Key Points Incidence Clinical Findings Differential Diagnosis Evaluation Therapy Incidence, Epidemiology, and Etiology Pathogenesis Molecular Pathogenesis Animal Models of Chronic Myeloid Leukemia Clinical Presentation Chronic Phase Accelerated and Blastic Phases Diagnosis Diagnostic and Monitoring Procedures Important Landmarks for Response or Failure to Tyrosine Kinase Inhibitor Therapy Differential Diagnosis Prognosis Management General Imatinib Nilotinib Dasatinib Bosutinib Ponatinib Discontinuation of Tyrosine Kinase Inhibitor Therapy and Treatment-Free Remissions Omacetaxine Allogeneic Stem Cell Transplantation Imatinib Resistance Selection of Sequential Therapies Old Traditional Standards of Care Revisited Accelerated- and Blastic-Phase Chronic Myeloid Leukemia Special Situations Chronic Myeloid Leukemia–Like Morphology Without Detectable Ph-Positive Disease Pregnancy Other Considerations Future Directions References 99 Chronic Lymphocytic Leukemia Summary of Key Points Epidemiology Biology and Genetics Is CLL a Stem Cell Disease? Is IGHV Mutational Status the Differentiating Feature of Low- Versus High-Risk CLL? Is ZAP70 Expression a Surrogate for IGHV Mutational Status or Driver Gene in the Pathogenesis of CLL? B-Cell Receptor Signaling in the Pathogenesis of Chronic Lymphocytic Leukemia Is Chronic Lymphocytic Leukemia a Disease of Defective Apoptosis? Genetic Abnormalities Recurring Mutations in Chronic Lymphocytic Leukemia Immune Suppression in Development and Progression of Chronic Lymphocytic Leukemia Contribution of Microenvironment in Chronic Lymphocytic Leukemia Pathogenesis Clinical Presentation Diagnosis Staging and Prognostic Factors Imaging Studies and Predicting Chronic Lymphocytic Leukemia Outcome Thymidine Kinase Activity and β2-Microglobulin IGHV Mutational Status CD38 Expression ZAP70 Chromosomal Aberrations Select Gene Mutations Integration of Clinical and Molecular Markers How to Use Staging and Biomarkers Complications Autoimmune Complications Infectious Complications Secondary Malignancies Hypersensitivity to Insect Bites Initial Treatment Cytotoxic Chemotherapy and Combinations Chlorambucil Purine Analogues Combining Fludarabine With Alkylating Agents Bendamustine Rituximab Rituximab Chemoimmunotherapy Fludarabine and Rituximab Fludarabine-Cyclophosphamide-Rituximab Bendamustine-Rituximab Chlorambucil-Rituximab Ofatumumab Obinutuzumab Ibrutinib Recommendations for Initial Treatment Treatment of Patients With Relapsed Chronic Lymphocytic Leukemia Fludarabine-Cyclophosphamide-Rituximab in Relapsed Chronic Lymphocytic Leukemia Bendamustine-Rituximab in Relapsed Chronic Lymphocytic Leukemia Ibrutinib Idelalisib Venetoclax Ofatumumab in Relapsed Chronic Lymphocytic Leukemia Obinutuzumab for Relapsed Chronic Lymphocytic Leukemia Methylprednisolone and Rituximab in Relapsed Chronic Lymphocytic Leukemia Additional Agents in Development for Chronic Lymphocytic Leukemia Acalabrutinib Lenalidomide Chimeric Antigen Receptor T Cells Recommendations for Treatment of the Patient With Relapsed or Refractory Disease Hematopoietic Stem Cell Transplant for Chronic Lymphocytic Leukemia Myeloablative Allogeneic Stem Cell Transplantation Reduced-Intensity Conditioning Myeloablative Allogeneic Stem Cell Transplantation Richter Transformation and Prolymphocytic Transformation Key References References 100 Hairy Cell Leukemia Summary of Key Points Epidemiology Etiology and Pathogenesis Clinical Presentation Laboratory Evaluation Differential Diagnosis Treatment Indications Role of Splenectomy Chemotherapeutic Approaches Interferon Purine Analogue Therapy Pentostatin (2′-Deoxycoformycin) Cladribine (2-Chlorodeoxyadenosine) Immunosuppression With Purine Analogues CD20-Directed Therapy Prognosis Other Considerations in Management Evaluation of Minimal Residual Disease Treatment of Relapse Risk of Second Malignancies New Therapies General Principles of Management References Self-Assessment Review Questions Answers 101 Multiple Myeloma and Related Disorders Summary of Key Points Multiple Myeloma Monoclonal Gammopathy of Undetermined Significance (MGUS) Smoldering Multiple Myeloma (SMM) Waldenström Macroglobulinemia Systemic AL (Immunoglobulin Light Chain) Amyloidosis Solitary Plasmacytoma Multiple Myeloma Definition Epidemiology Pathogenesis Transition From Normal Plasma Cell to Monoclonal Gammopathy of Undetermined Significance Antigenic stimulation and immunosuppression Cytogenetic changes Progression to Malignancy Pathogenesis of Bone Lesions Clinical Features Investigation Identification of Monoclonal Proteins Serum protein electrophoresis and immunofixation Quantitative immunoglobulin studies Urine protein electrophoresis and immunofixation Serum free light chain assay Identification of Bone Disease Bone Marrow Studies Differential Diagnosis Prognosis Host Factors Stage Molecular Classification and Risk Stratification Management Initial Therapy Bortezomib-lenalidomide-dexamethasone Bortezomib-cyclophosphamide-dexamethasone Bortezomib-thalidomide-dexamethasone Lenalidomide-dexamethasone Melphalan-prednisone-thalidomide Bortezomib-melphalan-prednisone Melphalan-prednisone-lenalidomide Other regimens Choice of initial therapy Hematopoietic Stem Cell Transplantation Autologous stem cell transplantation Tandem transplantation. Allogeneic transplantation. Maintenance Therapy Treatment of Relapsed Multiple Myeloma Bortezomib Lenalidomide Carfilzomib Pomalidomide Panobinostat Daratumumab Elotuzumab Ixazomib Thalidomide and thalidomide-based regimens Glucocorticoids and alkylating agents Liposomal doxorubicin Emerging treatment options Choice of therapy in the relapsed setting Treatment of Plasma Cell Leukemia Supportive Care Prevention of Skeletal Lesions Treatment of Anemia Prevention of Infections Complications Hypercalcemia Bone Lesions, Fractures, and Spinal Cord Compression Renal Insufficiency Hyperviscosity Syndrome Monoclonal Gammopathy of Undetermined Significance Clinical Features and Differential Diagnosis Prognosis Risk Stratification of Monoclonal Gammopathy of Undetermined Significance Management Smoldering Multiple Myeloma Clinical Features and Differential Diagnosis Prognosis Management Waldenström Macroglobulinemia Diagnosis Prognosis Treatment Initial Therapy Relapsed Disease and Supportive Care Systemic AL (Immunoglobulin Light Chain) Amyloidosis Diagnosis Prognosis Treatment Solitary Plasmacytoma Diagnosis and Prognosis Treatment POEMS Syndrome Diagnosis Treatment Heavy Chain Diseases Gamma Heavy Chain Disease Alpha Heavy Chain Disease Mu Heavy Chain Disease Cryoglobulinemia Type I Cryoglobulinemia Type II Cryoglobulinemia Type III Cryoglobulinemia Key References References 102 Hodgkin Lymphoma Summary of Key Points Incidence Biologic Characteristics Staging Evaluation Primary Therapy Salvage Therapy Introduction Epidemiology and Etiology Pathology and Biology Clinical Manifestations, Evaluation, and Staging Primary Therapy Early-Stage Nonbulky Hodgkin Lymphoma Early-Stage Bulky Hodgkin Lymphoma Advanced-Stage Hodgkin Lymphoma Therapy of Hodgkin Lymphoma in Pregnancy Therapy of Hodgkin Lymphoma in Older Patients Therapy of Hodgkin Lymphoma in HIV Therapy of Lymphocyte-Predominant Hodgkin Lymphoma Treatment and Prognosis of Relapsed Disease Prognostic Significance of Pretransplant Positron Emission Computed Tomography/Computed Tomography Pretransplant Salvage Chemotherapy Posttransplant Maintenance Therapy Role of Allogeneic Stem Cell Transplantation New Drugs Late Complications of Therapy for Hodgkin Lymphoma Second Cancers Cardiovascular and Cerebrovascular Complications Fertility Screening Recommendations Controversies, Problems, and Challenges Conclusions Key References References 103 Non-Hodgkin Lymphomas Summary of Key Points Incidence Etiology and Biology Differential Diagnosis Staging Evaluation Primary Therapy Salvage Therapy Introduction Epidemiology and Risk Factors Incidence, Distribution, and Death Rates Risk Factors and Predisposing Conditions Diagnosis and Classification Classification of Lymphomas Molecular Genetics of Non-Hodgkin Lymphoma Staging and Prognosis Principles of Evaluation and Staging Prognostic Factors for Lymphoma Response Assessment Management Indolent B-Cell Lymphomas Follicular Lymphoma Localized follicular lymphoma Advanced follicular lymphoma Maintenance therapy in follicular lymphoma Transformed Follicular Lymphoma Marginal Zone Lymphomas Lymphoplasmacytic Lymphoma or Waldenström Macroglobulinemia Relapsed Therapy for Indolent B-Cell Lymphomas Aggressive B-Cell Lymphomas Diffuse Large B-Cell Lymphoma Pathogenesis Initial treatment of localized diffuse large B-cell lymphoma Initial treatment of advanced diffuse large B-cell lymphoma Primary Mediastinal B-Cell Lymphoma Burkitt Lymphoma High-Grade B-Cell Lymphomas Gray-Zone Lymphomas Primary Testicular Lymphomas Primary Central Nervous System Lymphoma Therapy for Relapsed Diffuse Large B-Cell Lymphomas Mantle Cell Lymphoma Pathogenesis Prognostic factors Induction therapy in younger patients Induction therapy in older patients Relapsed Mantle Cell Lymphoma Peripheral T-Cell Lymphomas Peripheral T-Cell Lymphoma, Not Otherwise Specified Anaplastic Large Cell Lymphoma Angioimmunoblastic T-Cell Lymphoma Extranodal Natural Killer Cell/T-Cell Lymphoma, Nasal Type Adult T-Cell Leukemia-Lymphoma Rare Extranodal T-Cell Lymphomas Late Complications of Treatment Key References References 104 Cutaneous T-Cell Lymphoma and Cutaneous B-Cell Lymphoma Summary of Key Points Incidence Biological Characteristics Staging Evaluation Therapy Introduction and Classification Epidemiology Etiology Cutaneous T-Cell Lymphoma Mycosis Fungoides and Sézary Syndrome Staging and Prognosis Transformed Mycosis Fungoides and Sézary Syndrome Biological Properties Immunopathogenesis Molecular pathogenesis CD30+ Lymphoproliferative Disorders Treatment Therapy for Cutaneous T-Cell Lymphoma Topical Therapy Phototherapy Electron-Beam Radiation Systemic Therapies Biological Therapies Denileukin diftitox. Histone deacetylase inhibitors. Monoclonal antibodies. Chemotherapy. Targeted antifolate therapy. Hematopoietic stem cell transplantation. CCR4 antibody: mogamulizumab. Investigational therapies Lenalidomide. Oligonucleotides (nuclear acid therapeutics). Proteasome inhibitors. Cutaneous B-Cell Lymphomas Therapy General Health Care Conclusion Key References References 105 Adult T-Cell Leukemia/Lymphoma Summary of Key Points Definition Virology and Pathogenesis Epidemiology Clinical Manifestations Histopathology Diagnosis Treatment and Prevention Introduction Virology and Pathogenesis Genomics Epidemiology of Human T-Cell Leukemia/Lymphotropic Virus Type I and Adult T-Cell Leukemia-Lymphoma Clinical Manifestations Laboratory Findings Histopathology Immunophenotype of Adult T-Cell Leukemia/Lymphoma Clinical Course and Treatment Interferon-α and Zidovudine Initial Therapy Combination Chemotherapy Central Nervous System Lesions of Aggressive Adult T-Cell Leukemia/Lymphoma Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma Response Criteria for Adult T-Cell Leukemia/Lymphoma Key References References Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Inside Back Cover
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