DeVita, Hellman, and Rosenbergs Cancer: Principles & Practice of Oncology
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Editura: LWW
Limba: Engleza
Nr. pagini: 2432
Coperta: Hardback
Dimensiuni: 22.1 x 7.1 x 28.2 cm
An aparitie: 2018
Table of Contents:
Part I: Molecular Biology of Cancer
1 The Cancer Genome
Introduction
Cancer Genes and Their Mutations
Identification of Cancer Genes
Cancer Gene Discovery by Sequencing Candidate Gene Families
Mutational Analysis of Exomes Using Sanger Sequencing
Next-Generation Sequencing and Cancer Genome Analysis
Whole-Genome Analysis Utilizing Second-Generation Sequencing
Whole-Exome Analysis Utilizing Second-Generation Sequencing
Somatic Alteration Classes Detected by Cancer Genome Analysis
Pathway-Oriented Models of Cancer Genome Analysis
Passenger and Driver Mutations
Networks of Cancer Genome Projects
The Genomic Landscape of Cancers
Single-Cell Genomics
Integrative Analysis of Cancer Genomics
Immunogenomics
The Cancer Genome and the New Taxonomy of Tumors
Liquid Biopsies as a Diagnosis Tool
Clinical Applications of Liquid Biopsies
Cancer Genomics and Drug Resistance
Perspectives of Cancer Genome Analysis
Acknowledgments
2 Molecular Methods in Cancer
Applications of Molecular Diagnostics in Oncology
Biomarker Genetics
Use of Biomarkers in Diagnosis
Use of Biomarkers in Prognosis
Use of Biomarkers in Predicting Response to Therapy
Use of Biomarkers in Therapeutic Disease Monitoring
Use of Biomarkers in Risk Assessment and Cancer Prevention
The Clinical Molecular Diagnostics Laboratory: Rules and Regulations
Specimen Requirements for Molecular Diagnostics
Molecular Diagnostics Testing Process
Targeted Mutation Analysis Methods
Polymerase Chain Reaction
Real-time Polymerase Chain Reaction
Reverse-Transcription Polymerase Chain Reaction
Allele-Specific Polymerase Chain Reaction
Fragment Analysis
Sanger Sequencing
Pyrosequencing
Methylation Analysis
Microsatellite Instability Analysis/Assessment of Mismatch Repair Deficiency
Fluorescence In Situ Hybridization
Whole-genome Analysis Methods
Next-Generation Sequencing
Genomic Microarrays
Expression Panels
Immunohistochemistry for Tumor Biomarkers
PD-L1
ALK and ROS1
BRAF V600E
Cell-Free DNA Technologies
3 Hallmarks of Cancer: An Organizing Principle for Cancer Medicine
Introduction
Hallmark Capabilities, in Essence
Sustaining Proliferative Signaling
Evading Growth Suppressors
Resisting Cell Death
Enabling Replicative Immortality
Inducing Angiogenesis
Activating Invasion and Metastasis
Reprogramming Energy Metabolism
Evading Immune Destruction
Two Ubiquitous Characteristics Facilitate the Acquisition of Hallmark Capabilities
An Enabling Characteristic: Genome Instability and Mutation
An Enabling Characteristic: Tumor-Promoting Inflammation
The Constituent Cell Types of the Tumor Microenvironment
Cancer-Associated Fibroblasts
Endothelial Cells
Pericytes
Immune Inflammatory Cells
Stem and Progenitor Cells of the Tumor Stroma
Heterotypic Signaling Orchestrates the Cells of the Tumor Microenvironment
Coevolution of the Tumor Microenvironment During Carcinogenesis
Cancer Cells, Cancer Stem Cells, and Intratumoral Heterogeneity
Therapeutic Targeting of the Hallmarks of Cancer
Conclusion and a Vision for the Future
Acknowledgment
4 Microbiome and Cancer
Introduction
Cancer as a Disease of the Metaorganism
Bacteria as Cause of Cancer
Helicobacter pylori and Stomach Cancer
Colorectal Cancer
Tumors in Tissues Not Directly Colonized by the Microbiota
The Microbiota Modulates Cancer-Predisposing Conditions and Comorbidity
Bacteria as Cancer Drugs
Microbiota and Drug Metabolism
Microbiota and Chemotherapy
Microbiota and Immunotherapy
Immune Checkpoint Blockers: Anti-CTLA-4
Immune Checkpoint Blockers: Anti-PD-1/PD-L1
Looking Forward
5 Cancer Susceptibility Syndromes
Introduction
Principles of Cancer Susceptibility
The “Two-Hit” Paradigm
What Is the Function of a Tumor Suppressor?
Haploinsufficiency and Compound Haploinsufficiency
Genetic Testing
Cancer Susceptibility Syndromes
Retinoblastoma
Most Prevalent Syndromes
Other Syndromes, by Function
Principles of Cancer Chemoprevention
Emerging Knowledge and New Lessons
Germline Mutations in Sporadic Cancer
Weak Modifiers
Epigenetic Factors
Role of Noncoding RNAs
The Regulatory Genome
High-Throughput Methods for Understanding Cancer Variants
Conclusion
Part II: Etiology and Epidemiology of Cancer
Section 1 Etiology of Cancer
6 Tobacco
Introduction
Epidemiology of Tobacco and Cancer
Tobacco Use Behaviors
Evolution of Tobacco Products
Carcinogens in Tobacco Products and Processes of Cancer Development
Compounds of Particular Concern
How Tobacco Use Leads to Cancer
Conclusion
7 Oncogenic Viruses
Principles of Tumor Virology
Papillomaviruses
History
Tissue Tropism and Gene Functions
Human Papillomavirus Vaccines
Oropharyngeal Cancer
Nonmelanoma Skin Cancer
Bladder Cancer
Polyomaviruses
History
BK Polyomavirus
Merkel Cell Polyomavirus
Other Human Polyomaviruses
Epstein-Barr Virus
History
Epstein-Barr Virus Life Cycle
Lymphomas
Carcinomas
Prevention and Treatment
Kaposi Sarcoma Herpesvirus
History and Epidemiology
Kaposi Sarcoma–Associated Herpesvirus in Kaposi Sarcoma
Lymphoproliferative Disorders
Animal and Human Retroviruses
Human T-Cell Leukemia Virus Epidemiology
Human T-Cell Leukemia Virus Molecular Biology
Clinical Characteristics and Treatment of Human T-lymphotropic Virus 1–Associated Malignancies
Hepatitis Viruses
Hepatitis B Virus
Hepatitis C Virus
Hepatitis Virus Pathogenesis
Clinical Characteristics and Treatment of Hepatitis Virus–Associated Malignancies
Conclusion
8 Inflammation
Introduction
Tumor-Intrinsic Inflammation
Tumor-Extrinsic Inflammation
Inflammatory Cell Subsets in the Cancer Microenvironment
Macrophages
T cells
Neutrophils
Myeloid-Derived Suppressor Cells
Dendritic Cells
Fibroblasts
Inflammatory Molecular Mediators in Cancer
Chemokines
Interleukins
Interferon
Tumor Necrosis Factor
Prostaglandin E2
Vascular Endothelial Growth Factor
Cellular Mechanisms of Inflammation in Cancer
Tumor Transformation
Tumor Epithelial–Mesenchymal Transition and Stemness
Tumor Growth and Survival
Tumor Angiogenesis
Molecular Mechanisms of Inflammation in Cancer
Nuclear Factor-Kappa Beta
STAT1 and STAT3
Inflammasomes
Toll-like Receptors
Inflammation as a Therapeutic Target
9 Chemical Factors
Introduction
Initial Identification and Characterization of Carcinogens
Determining Carcinogenicity
International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans
National Toxicology Program Report on Carcinogens
Characteristics of Chemical Carcinogens
Chemical Classes and Sources
Pharmacokinetics and Mechanisms of Carcinogens
The Cancer Genome Atlas and Chemical Carcinogenesis
Outlook
10 Physical Factors
Introduction
Ionizing Radiation
Mechanisms of Damage Induction
Cellular Responses
Cancer Risks
Ultraviolet Light
Mechanisms of Damage Induction
Cellular Responses
Cancer Risks
Nonmelanoma Skin Cancer
Melanoma
Photoimmunosuppression
Radiofrequency and Microwave Radiation
Mechanism of Damage Induction
Cancer Risks
Electromagnetic Fields
Mechanisms of Damage Induction
Cancer Risks
Potential Cancer Risks from Mobile Phone Usage
Asbestos
Mechanisms of Damage Induction
Cellular and Tissue Responses
Cancer Risks
Nanoparticles
Mechanisms of DNA Damage Induction
Cellular Responses
Cancer Risks
11 Dietary Factors
Introduction
Methodologic Challenges
Study Types and Biases
Ecologic Studies
Migrant Studies
Case-Control Studies
Cohort Studies
Randomized Clinical Trials
Diet Assessment Instruments
The Role of Individual Food and Nutrients in Cancer Etiology
Energy
Alcohol
Dietary Fat
Fruits and Vegetables
Fiber
Other Foods and Nutrients
Red Meat
Milk, Dairy Products, and Calcium
Coffee
Vitamin D
Folate
Carotenoids
Selenium
Soy Products
Carbohydrates
Dietary Patterns
Diet during Early Phases of Life
Diet after a Diagnosis of Cancer
The Microbiome
Summary
Limitations
Future Directions
Recommendations
12 Obesity and Physical Activity
Introduction
Obesity
Obesity and Cancer Risk
Obesity and Cancer Outcomes
Obesity and Cancer Treatment–Related Complications
Interventions
Physical Activity
Physical Activity and Cancer Risk
Physical Activity and Cancer Outcomes
Sedentary Behavior
Interventions
Mechanistic Data
Weight and Physical Activity Guidelines
American Society of Clinical Oncology Obesity Initiative
Conclusion
Section 2 Epidemiology of Cancer
13 Epidemiologic Methods
Introduction
Analytical Studies
Ecologic Studies
Cross-sectional Studies
Cohort Studies
Case-Control Studies
Interpretation of Epidemiologic Findings
Cancer Outcomes Research
Molecular Epidemiology
Studies of Genetic Factors
Consideration of Research Design
Analysis of Biomarkers
14 Global Cancer Incidence and Mortality
Introduction
Geographic and Temporal Variations in Risk
Studies of Migrants
Implications of These Variations in Risk
Data Sources
Cancer Incidence
Cancer Mortality
Global Estimates of Cancer Risk and Burden
Measures of Burden
Number of New Cancer Cases and Deaths
Prevalence
Measures of Risk
Incidence and Mortality Rates
Cumulative Risk
Survival
Demographic Factors that Affect Risk
Sex
Socioeconomic Status
Race and Ethnicity
Geographic Location
Temporal Trends
Incidence and Mortality Patterns for Common Cancers
Relationship of Risk to Environmental Exposures
Lung Cancer
Female Breast Cancer
Colorectal Cancer
Stomach Cancer
Prostate Cancer
Liver Cancer
Cervical Cancer
Uterine Corpus Cancer
Issues in Interpreting Temporal Trends
Conclusion
Part III: Cancer Therapeutics
15 Precision Medicine in Oncology
Introduction
Approach to Precision Medicine in Oncology
Next-Generation DNA Sequencing for Precision Oncology
Broadening the Spectrum of Molecular Characterization
Preclinical Models to Inform Precision Oncology
Role of Molecular Pharmacodynamics and Diagnostics in Precision Oncology
Human Biospecimens for Molecular Characterization
Molecular Pharmacodynamics in Precision Oncology
Predictive Diagnostic Assays
Precision Oncology Clinical Trials and Trial Designs
Imaging and Precision Oncology
Precision Prevention
Future Prospects
16 Essentials of Radiation Therapy
Introduction
Biologic Aspects of Radiation Oncology
Radiation-Induced DNA Damage
Cellular Responses to Radiation-Induced DNA Damage
Chromosome Aberrations Result from Faulty DNA Double-Strand Break Repair
Membrane Signaling
The Effect of Radiation on Cell Survival
Factors that Affect Radiation Response
The Fundamental Principles of Radiobiology
Drugs that Affect Radiation Sensitivity
Antimetabolites
Platinums and Temozolomide
Taxanes
Molecularly Targeted Agents
Immunotherapy
Radiation Protection
Radiation Physics
Physics of Photon Interactions
Photon Beam Generation and Treatment Delivery
Treatment Beam Characteristics and Dose Calculation Algorithms
Treatment Planning
Other Treatment Modalities
Clinical Applications of Radiation Therapy
Clinical Application of Types of Radiation
Treatment Intent
Fractionation
Adverse Effects
Principles of Combining Anticancer Agents with Radiation Therapy
17 Cancer Immunotherapy
Introduction
Interferon-α
Interleukin-2
Talimogene Laherparepvec
Granulocyte Macrophage Colony-stimulating Factor
Tumor-Infiltrating Lymphocytes
Checkpoint Inhibitors—Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell Death Protein 1
Cytotoxic T-Lymphocyte Antigen 4 Blockade
Programmed Cell Death Protein 1 and Programmed Cell Death Protein Ligand 1 Blockade
Melanoma
Non–small-cell Lung Cancer
Mismatch-Repair Deficient or Microsatellite Instability-High Cancers
Renal Cell Carcinoma
Hodgkin Lymphoma
Head and Neck Squamous Cell Carcinoma
Urothelial Carcinoma
Merkel Cell Carcinoma
Hepatocellular Carcinoma
Gastric Cancer
Cervical Cancer
Primary Mediastinal Large B-Cell Lymphoma
Dosing
Vaccines
Sipuleucel-T
Conclusion
18 Pharmacokinetics and Pharmacodynamics of Anticancer Drugs
Introduction
Pharmacokinetic Concepts
Absorption
Disposition
Dose Proportionality
Pharmacodynamic Concepts
Variability in Pharmacokinetics/ Pharmacodynamics
Body Size and Body Composition
Age
Pathophysiologic Changes
Sex Dependence
Drug Interactions
Inherited Genetic Factors
Dose Adaptation Using Pharmacokinetic/Pharmacodynamic Principles
Therapeutic Drug Monitoring
Feedback-Controlled Dosing
19 Pharmacogenomics
Introduction
Pharmacogenomics of Tumor Response
Pathway-Directed Anticancer Therapy
Genetic-Guided Therapy: Practical Issues in Somatic Analysis
Pharmacogenomics of Chemotherapy Drug Toxicity
Thiopurine Methyltransferase
Dihydropyrimidine Dehydrogenase
Conclusions and Future Directions
20 Alkylating Agents
Historical Perspectives
Chemistry
Classification
Alkyl Sulfonates
Aziridines
Triazines
Nitrogen Mustards
Nitrosoureas
Clinical Pharmacokinetics/Pharmacodynamics
Therapeutic Uses
Toxicities
Nausea and Vomiting
Bone Marrow Toxicity
Renal and Bladder Toxicity
Interstitial Pneumonitis and Pulmonary Fibrosis
Gonadal Toxicity, Teratogenesis, and Carcinogenesis
Alopecia
Allergic Reactions
Immunosuppression
Complications with High-Dose Alkylating Agent Therapy
Alkylating Agent–Steroid Conjugates
Drug Resistance and Modulation
Future Perspectives
21 Platinum Analogs
Introduction
History
Platinum Chemistry
Platinum Complexes after Cisplatin
Carboplatin
Oxaliplatin
Newer Platinum Structures
Mechanism of Action
DNA Adduct Formation
Ribosome Biogenesis Stress
DNA Intrastrand Cross-links
Cellular Responses to Platinum-Induced DNA Damage
Cell Fate
DNA Damage Recognition
DNA Damage Signaling
The PARP inhibitors olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are approved by the U.S. Food and Drug Administration (FDA) for the treatment of platinum-sensitive ovarian cancer. Olaparib has also recently been approved for use in triple-negative breast cancer. PARP inhibitors are in clinical development to treat other BRCA-associated malignancies including pancreatic and prostate cancers.
Role of Lipid Signaling
Platinum Compounds and Immunotherapy
Mechanisms of Resistance
Reduced Accumulation
Inactivation
Increased DNA Repair
Autophagy
Increased DNA Damage Tolerance
Cancer Stem-Like Cells
Clinical Pharmacology
Pharmacokinetics
Pharmacodynamics
Pharmacogenomics
22 Antimetabolites
Antifolates
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
5-Fluoropyrimidines
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Biomodulation of 5-FU
Toxicity
Capecitabine
Clinical Pharmacology
Toxicity
Trifluridine/Tipiracil
Clinical Pharmacology
Toxicity
Cytarabine
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
Gemcitabine
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
6-Thiopurines
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
Fludarabine
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
Cladribine
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
Clofarabine
Mechanism of Action
Mechanisms of Resistance
Clinical Pharmacology
Toxicity
23 Topoisomerase-Interacting Agents
Biochemical and Biologic Functions of Topoisomerases
Classification of Topoisomerases
Biochemical Characteristics and Cleavage Complexes of the Different Topoisomerases
Differential Topoisomerization Mechanisms: Swiveling versus Strand Passage, DNA versus RNA Topoisomerases
Topoisomerase Inhibitors as Interfacial Poisons
Topoisomerase Inhibitors Act as Interfacial Inhibitors by Binding at the Topoisomerase–DNA Interface and Trapping Topoisomerase Cleavage Complexes
TOP1cc-Targeted Drugs (Camptothecin and Indenoisoquinoline Derivatives) Kill Cancer Cells by Replication Collisions
Cytotoxic Mechanisms of TOP2cc-Targeted Drugs (Intercalators and Demethylepipodophyllotoxins)
Topoisomerase I Inhibitors: Camptothecins and Beyond
Irinotecan
Topotecan
Camptothecin Conjugates and Analogs
Noncamptothecin Topoisomerase I Inhibitors
Topoisomerase II Inhibitors: Intercalators and Nonintercalators
Doxorubicin
Liposomal Doxorubicin
Daunorubicin
Epirubicin
Idarubicin
Cardiac Toxicity of Anthracyclines
Mitoxantrone
Dactinomycin
Epipodophyllotoxins
Etoposide
Teniposide
Therapy-Related Secondary Acute Leukemia
Future Directions
24 Antimicrotubule Agents
Microtubules
Taxanes
Mechanism of Action
Clinical Pharmacology
Drug Interactions
Toxicity
Vinca Alkaloids
Mechanism of Action
Clinical Pharmacology
Drug Interactions
Toxicity
Microtubule Antagonists
Estramustine Phosphate
Epothilones
Maytansinoids and Auristatins: DM1, DM4, MMAE, MMAF
Mitotic Motor Protein Inhibitors
Aurora Kinase and Polo-Like Kinase Inhibitors
Kinesin Spindle Protein Inhibitor
Mechanisms of Resistance to Microtubule Inhibitors
Summary
25 Kinase Inhibitors as Anticancer Drugs
Introduction
Validating Mutated Kinases as Cancer Drug Targets—the Development of Imatinib for Patients with Chronic Myelogenous Leukemia and Gastrointestinal Stromal Tumors
The Development of HER2-Targeted Therapies in Breast and Other Cancers
The Development of EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Identifying Therapeutic Targets in EGFR Wildtype Lung Cancers
ALK Fusions
ROS1 Fusions
RET Fusions
MET
BRAF V600E–Mutant Lung Cancers and Additional Molecularly Defined Populations
RAF and MEK Inhibitors for BRAF-Mutant Tumors
PI3 Kinase Pathway Inhibitors
One Target or Several: Multitargeted Kinase Inhibitor Therapy in Renal Cell Carcinoma and Medullary Thyroid Cancer
CDK4/6 Inhibitors
Bruton Tyrosine Kinase Inhibitors
A Potential Pan Cancer Drug Target—TRK Inhibitors
Future Directions
26 Histone Deacetylase Inhibitors and Demethylating Agents
Introduction
Epigenetic Abnormalities and Gene Expression Changes in Cancer
Abnormal Gene Silencing
Chromatin in Gene Regulations
Enzymes Regulating DNA Methylation, Demethylation, and Histone Acetylation
Reversal of Layers of Gene Silencing
DNA Methyltransferase Inhibitors
Histone Deacetylase Inhibitors
Epigenetic Therapy for Hematologic Malignancies
DNA Methyltransferase Inhibitors
Combining Inhibitors in the Treatment of Hematologic Malignancies
Epigenetically Targeted Therapy in Solid Tumors
New Approaches to Epigenetic Therapy
27 Proteasome Inhibitors
Biochemistry of the Ubiquitin-Proteasome Pathway
Proteasome Inhibitors
Chemical Classes of Proteasome Inhibitors in Clinical Development
Preclinical Activity of Proteasome Inhibitors
Pharmacokinetics and Pharmacodynamics of Proteasome Inhibitors in Animals
Proteasome Inhibitors in Cancer
Clinical Activity of Proteasome Inhibitors
Clinical Activity in Other Cancers
Mechanisms of Resistance
28 Poly(ADP-Ribose) Polymerase Inhibitors for Tumors with Defects in DNA Repair
Introduction
Cellular DNA Repair Pathways
BRCA1 and BRCA2 Mutations and DNA Repair
The Development of PARP Inhibitors
PARP-1 Inhibition as a Synthetic Lethal Therapeutic Strategy for the Treatment of BRCA-Deficient Cancers
Initial Clinical Results Testing Synthetic Lethality of PARP Inhibitors and BRCA Mutation
PARP Inhibitors Approved for Clinical Use
The Use of PARP Inhibitors in Non-BRCA Germline Mutant Cancers
Mechanisms of Resistance to PARP Inhibitors
Future Prospects
29 Miscellaneous Chemotherapeutic Agents
Homoharringtonine and Omacetaxine
L-Asparaginase
Bleomycin
Procarbazine
Dactinomycin
Vismodegib
Ado-Trastuzumab Emtansine
Sirolimus and Temsirolimus
Everolimus
Thalidomide, Lenalidomide, and Pomalidomide
Thalidomide
Lenalidomide
Pomalidomide
Miscellaneous Agents with Potential for Repurposable Chemotherapeutic Use
Nelfinavir
Propranolol
Metformin
Statins
30 Hormonal Agents
Introduction
Selective Estrogen Receptor Modulators
Tamoxifen
Endoxifen
Toremifene
Raloxifene
Fulvestrant
Aromatase Inhibitors
Letrozole and Anastrozole
Exemestane
Resistance to Endocrine-Targeted Therapy in Breast Cancer
Combination and Developing Strategies to Overcome Endocrine Resistance in Breast Cancer
Gonadotropin-Releasing Hormone Analogs
Gonadotropin-Releasing Hormone Analogs
Gonadotropin-Releasing Hormone Antagonists
Antiandrogens
Flutamide
Bicalutamide
Nilutamide
Resistance to Androgen Therapies in Prostate Cancer
Abiraterone Acetate
Enzalutamide
Androgen-Targeted Therapies in Development
Other Sex Steroid Therapies
Fluoxymesterone
Estrogens: Diethylstilbestrol and Estradiol
Medroxyprogesterone and Megestrol
Other Hormonal Therapies
Octreotide
31 Monoclonal Antibodies
Introduction
Immunoglobulin Structure
Structural and Functional Domains
Modified Antibody-Based Molecules
Factors Regulating Antibody-Based Tumor Targeting
Antibody Size
Tumor Antigens
Half-Life/Clearance Rate
Glycosylation
Unconjugated Antibodies
Cell-Mediated Cytotoxicity
Complement-Dependent Cytotoxicity
Altering Signal Transduction
Immunoconjugates
Antibody–Drug Conjugates
Radioimmunoconjugates
Antibodies Approved for Use in Solid Tumors
Trastuzumab
Pertuzumab
Cetuximab
Panitumumab
Necitumumab
Bevacizumab
Ado-Trastuzumab Emtansine
Ramucirumab
Denosumab
Antibodies Used in Hematologic Malignancies
Rituximab
Ofatumumab
Alemtuzumab
Brentuximab Vedotin
Inotuzumab Ozogamicin
Obinutuzumab
Blinatumomab
Daratumumab
Elotuzumab
Dinutuximab
Olaratumab
Conclusion
32 Immunotherapy Agents
Introduction
Human Tumor Antigens
Mutanome-Associated Neoantigens
Tumor Vaccines
Personalized Neoantigen Vaccination
Immune Checkpoint Inhibitors
Other Immune Checkpoint Inhibitors in Development
Oncolytic Viruses
Talimogene Laherparepvec
Other Oncolytic Viruses
Factors to Activate Immune Effector Cells
Cytokines
IL-2 Variant Molecules
Signaling Modulation
STAT3 Inhibition
PI3Kδ Inhibitors
PI3Kγ Inhibitors
Chemokine Inhibitors
Soluble Factors
IDO Inhibition
Arginase Inhibitor
TGF-β Kinase Inhibitors
Adenosine A2α Receptor Axis
Adenosine Receptor Inhibitors
Innate Immune Modulation
Pathogen-Associated Molecular Patterns, Damage-Associated Molecular Patterns, and Pattern Recognition Receptors
Toll-Like Receptor Modulators
STING Agonists
Anti-CD47 Monoclonal Antibodies
Colony-Stimulating Factor 1 Receptor Inhibition
Bifunctional Fusion Proteins
Immunocytokines
Adoptive Cell Therapy
Chimeric Antigen Receptor T-Cell Therapy
Part IV: Cancer Prevention and Screening
33 Tobacco Use and the Cancer Patient
Introduction
Tobacco Use Epidemiology, Addiction, and Tobacco Product Evolution
Electronic Nicotine Delivery Systems, or Electronic Cigarettes
Defining Tobacco Use by the Cancer Patient
Tobacco Use and Cessation by the Cancer Patient
Smoking Cessation in the Context of Lung Cancer Screening
The Clinical Effects of Smoking on Cancer Patients
The Effect of Smoking and Smoking Cessation on Overall Mortality or Overall Survival
The Effect of Smoking on Cancer Recurrence and Cancer-Related Mortality
The Effect of Smoking and Cessation on Cancer Treatment Toxicity
The Effect of Smoking and Cessation on Risk of Second Primary Cancer
Human Papillomavirus, Epidermal Growth Factor Receptor, Anaplastic Lymphoma Kinase, Programmed Cell Death Protein 1, and Smoking
Summarizing the Clinical Effects of Smoking and Cessation in Cancer Patients
Addressing Tobacco Use by the Cancer Patient
Smoking Cessation Guidelines
Implementing Smoking Cessation into Clinical Practice
Pharmacologic Treatment for Smoking Cessation
Empirically Tested Cessation Interventions in Cancer Patients
Improving Tobacco Assessment and Cessation Support by Oncologists
Research Considerations and the Future of Addressing Tobacco Use by Cancer Patients
34 Role of Surgery in Cancer Prevention
Introduction
Risk-Reducing Surgery in Breast Cancer
Identifying High-Risk Patients
Management Options for High-Risk Patients
Hereditary Diffuse Gastric Cancer
Surgical Prophylaxis of Hereditary Ovarian and Endometrial Cancer
Hereditary Ovarian Cancer (BRCA1, BRCA2)
Hereditary Endometrial Cancer (Lynch Syndrome)
Gynecologic Cancer Risk in Very Rare Hereditary Cancer Syndromes
Multiple Endocrine Neoplasia Type 2
Gene Carriers
RET Genotype-Phenotype Correlations
Risk-Reducing Thyroidectomy in RET Mutation Carriers
Follow-up
Conclusions
Hereditary Colorectal Cancer Syndromes: Familial Adenomatous Polyposis, MUTYH-Associated Polyposis, and Lynch Syndrome
Familial Adenomatous Polyposis
MUTYH-Associated Polyposis
Lynch Syndrome
35 Cancer Risk–Reducing Agents
Why Cancer Prevention as a Clinical Oncology Discipline
Defining Cancer Risk–Reducing Agents (Chemoprevention)
Identifying Potential Cancer Risk–Reducing Agents
Preclinical Development of Cancer Risk–Reducing Agents
Biochemical Prescreening Assays
Preclinical In Vivo Models for Cancer Risk–Reducing Agent Efficacy Testing
Clinical Development of Cancer Risk–Reducing Agents
Special Features of Cancer Risk–Reducing Agent Development
Phases of Cancer Risk–Reducing Agent Development
Micronutrients
Definition
Retinoids, Carotenoids, and Antioxidant Nutrients
Folic Acid and Other B Vitamins
Calcium and Vitamin D
Summary and Conclusion: Micronutrients
Anti-Inflammatory Drugs
Mechanism
Posttranslational Pathway Targets
Selective Estrogen Receptor Modulators
Aromatase Inhibitors
Breast Cancer Risk Reductive Use Counseling
5α-Steroid Reductase Inhibitors
Difluoromethylornithine
Statins
Metformin
Diet-Derived Natural Products
Mechanism
Preclinical and Clinical Anticarcinogenesis Efficacy
Pharmacologic versus Dietary Equivalent Dosing
Anti-Infectives
Helicobacter pylori
Multiagent Approaches to Cancer Risk Reduction
36 Prophylactic Cancer Vaccines
Introduction
Overview of Infectious Agents in Cancer
Hepatitis B Vaccines
Human Papillomavirus Vaccines
Prospects for Prophylactic Vaccines against Other Oncogenic Microbes
Helicobacter pylori
Epstein-Bar Virus
Hepatitis C Virus
Kaposi Sarcoma Virus
Other Infectious Agents
Vaccines for Cancers of Noninfectious Etiology: Tumor-Specific and Tumor-Associated Target Antigens
Therapeutic Cancer Vaccines Have Set the Stage for Preventative Cancer Vaccines
Prophylactic Vaccines for Cancers of Noninfectious Etiology
37 Cancer Screening
Introduction
Performance Characteristics of a Screening Test
Assessing a Screening Test
Assessing Screening Outcomes
Screening Guidelines and Recommendations
Breast Cancer Screening
Effectiveness of Breast Cancer Screening
Screening Women at Higher Risk
Newer Screening Technologies
Ductal Carcinoma In Situ
Breast Screening Recommendations
Gastrointestinal Tract Cancers 460
Colon Cancer Screening
Screening for Other Gastrointestinal Malignancies
Gynecologic Cancer
Cervical Cancer Screening
Ovarian Cancer Screening
Endometrial Cancer Screening
Lung Cancer Screening
Prostate Cancer Screening
Does Prostate Cancer Treatment Prevent Deaths?
Prospective Randomized Screening Trials
Screening Recommendations
Skin Cancer Screening
Recommendations of Experts
38 Genetic Counseling
Introduction
Who Is a Candidate for Cancer Genetic Counseling?
Components of the Cancer Genetic Counseling Session
Precounseling Information
Family History
Dysmorphology Screening
Risk Assessment
Genetic Testing
Options for Surveillance, Risk Reduction, and Tailored Treatment
Follow-up
Issues in Cancer Genetic Counseling
Genetic Test Selection and Approaches
Management of the Patient with a Pathogenic Variant in a Moderate-Risk or Lesser Known Gene
Genetic Testing in Children
Reproductive Issues
Potential Germline Implications of Tumor Genomic Profiling
Changes in Delivery Models
Direct-to-Consumer Genetic Testing
Psychosocial Issues
Confidentiality
Insurance and Discrimination Issues
Future Directions
Whole-Genome Sequencing and Whole-Exome Sequencing
General Population Testing
CRISPR
Conclusion
Part V: Practice of Oncology
39 Design and Analysis of Clinical Trials
Introduction
Phase I Clinical Trials
Accelerated Titration Designs
Continual Reassessment Methods
Other Methods
Phase II Clinical Trials
Patient Selection
Single-Arm Phase II Trials
Design of Phase III Clinical Trials
End Points
Patient Eligibility
Randomization
Stratification
Sample Size
Factorial Designs
Noninferiority Trials
Bayesian Methods
Analysis of Phase III Clinical Trials
Intention-to-Treat Analysis
Interim Analyses
Significance Levels, Hypothesis Tests, and Confidence Intervals
Calculation of Survival Curves
Multiple Comparisons
Reporting Results of Clinical Trials
False-positive Reports in the Literature
Meta-analysis
40 Assessment of Clinical Response
Introduction
From Calipers and Rulers in Lymphoma to Diagnostic Imaging and the Bidimensional World Health Organization Criteria and the One-Dimensional Response Evaluation Criteria in Solid Tumors
Assessing Response
Response Evaluation Criteria in Solid Tumors 1.1
Variations of the Response Evaluation Criteria in Solid Tumors
Alternate Response Criteria
Determining Outcome
Overall Response Rate and Stable Disease
Progression-Free Survival, Time to Progression, and Time to Treatment Failure
Overall Survival
Kaplan-Meier Plots
Hazard Ratios
Forest Plots
Beyond Dichotomized Data
41 Vascular Access
Introduction
Catheter Types
External Catheters
Nontunneled Catheters
Tunneled Catheters
Peripherally Inserted Central Catheter
Implantable Devices
Implantable Ports
Implantable Infusion Pumps
Catheter Selection
Pediatric Patients
Insertion Techniques
Catheter-Related Complications
Immediate Complications
Venous Thrombosis
Catheter Infections
42 Endoscopic and Robotic Surgery
Introduction
Physiologic Effects of Endoscopic Surgery
Immunologic Effects
Applications of Endoscopic and Robotic Surgery
Diagnosis
Staging
Treatment
Palliation
Advantages and Disadvantages
Special Topics
Thoracic Surgical Oncology
Standardization of Minimally Invasive Thoracic Surgery
Lobectomy for Lung Cancer
Esophagectomy for Esophageal Cancer
Gastrointestinal and Hepatopancreatobiliary Cancers
Colon and Rectal Cancer
Hepatobiliary and Pancreas Cancer
Genitourinary and Gynecologic Oncology
Hysterectomy for Endometrial and Cervical Cancer
Robotic-Assisted Radical Prostatectomy for Prostate Cancer
Laparoscopic and Robotic Nephrectomy
Emerging Techniques
Natural Orifice Transluminal Endoscopic Surgery and Transoral Robotic Surgery
Conclusion
43 Tumor Biomarkers
Introduction
Uses for Tumor Biomarker Tests
What Are the Criteria to Incorporate a Tumor Biomarker Test into Clinical Practice?
Tumor Biomarker Tests that Are Accepted for Routine Clinical Utility
Special Circumstances
Pharmacogenomics
Tumor Biomarker Tests of Radiation Response
Conclusion
Section 1 Cancer of the Head and Neck
44 The Molecular Biology of Head and Neck Cancers
Incidence, Risk Factors, and Etiology
Oral Tongue Cancer in Young Patients
High-Risk HPV in Oropharyngeal Cancer
Molecular Mechanisms in HNSCC
The Cancer Genome Atlas Project
Inhibition of HNSCC Immune Escape
Cancer Stem Cells
45 Cancer of the Head and Neck
Incidence and Etiology
Anatomy and Pathology
Natural History
Patterns of Spread
Diagnosis
Staging
Principles of Treatment for Squamous Cell Carcinoma
General Principles for Selection of Treatment
Transoral Robotic Surgery
Survival Benefits of Head and Neck Cancer Patients Receiving Treatment at Centers with Expertise
Management
Primary Site
NECK
Clinically Negative Neck
Clinically Positive Neck Lymph Nodes
Chemotherapy
Chemotherapy for Recurrent or Metastatic Disease
General Principles of Combining Modalities
Surgery plus Radiation Therapy
Chemotherapy as Part of Curative Treatment
Induction Chemotherapy
Concurrent Chemotherapy and Radiation for Gross Disease
Nasopharynx Cancer
Organ Preservation
Adjuvant Therapy after Surgery
Toxicity Reduction
Follow-up
ORAL CAVITY
Lip
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Treatment
Results of Treatment
Complications of Treatment
Floor of the Mouth
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Treatment
Results of Treatment
Follow-up
Complications of Treatment
Oral Tongue
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Differential Diagnosis
Treatment
Results of Treatment
Complications of Treatment
Buccal Mucosa
Epidemiology
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Differential Diagnosis
Treatment
Results of Treatment
Complications of Treatment
Gingiva and Hard Palate (Including Retromolar Trigone)
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Differential Diagnosis
Treatment
Results of Treatment
Complications of Treatment
OROPHARYNX
Anatomy
Tonsillar Fossa/Glossotonsillar Sulcus
Base of Tongue
Soft Palate
Posterior Pharyngeal Wall
Pathology
Patterns of Spread
Tonsillar Fossa
Base of Tongue
Soft Palate
Posterior Pharyngeal Wall
Clinical Picture
Tonsillar Fossa
Base of Tongue
Soft Palate
Staging
Treatment: Tonsillar Fossa
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Management of Recurrence
Results of Treatment: Tonsillar Area
Complications of Treatment: Tonsillar Area
Radiation Therapy
Surgical Treatment
Treatment: Base of Tongue
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Management of Recurrence
Results of Treatment: Base of Tongue
Follow-up: Base of Tongue
Complications of Treatment: Base of Tongue
Surgical Complications
Complications of Irradiation
Treatment: Soft Palate
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Management of Recurrence
Results of Treatment: Soft Palate
Complications of Treatment: Soft Palate
Surgical Complications
Complications of Irradiation
LARYNX
Anatomy
Pathology
Patterns of Spread
Supraglottic Larynx
True Vocal Cord
Subglottic Larynx
Lymphatic
Clinical Picture
Presenting Symptoms
Physical Examination
Differential Diagnosis and Staging
Treatment: Vocal Cord Carcinoma
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Management of Recurrence
Treatment: Supraglottic Larynx Carcinoma
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Combined Treatment Policies
Management of Recurrence
Treatment: Subglottic Larynx Carcinoma
Results of Treatment
Treatment: Supraglottic Larynx Cancer
Complications of Treatment
HYPOPHARYNX: PHARYNGEAL WALLS, PYRIFORM SINUS, AND POSTCRICOID PHARYNX
Anatomy
Pathology
Patterns of Spread
Posterior Pharyngeal Wall
Lateral Pharyngeal Wall
Pyriform Sinus
Postcricoid Pharynx
Lymphatic
Clinical Picture
Staging
Treatment
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Combined Treatment Policies
Management of Recurrence
Results of Treatment
Pharyngeal Wall
Pyriform Sinus
Complications of Treatment
Posterior Pharyngeal Wall
Pyriform Sinus
NASOPHARYNX
Anatomy
Lymphatic
Pathology
Patterns of Spread
Primary
Lymphatic
Clinical Picture
Staging
Treatment
Selection of Treatment Modality
Irradiation Technique
Management of Recurrence
Results of Treatment
Follow-up
Complications of Treatment
NASAL VESTIBULE, NASAL CAVITY, AND PARANASAL SINUSES
Anatomy
Lymphatic
Pathology
Benign Tumors
Malignant Tumors
Patterns of Spread
Nasal Vestibule
Nasal Cavity and Paranasal Sinuses
Clinical Picture
Nasal Vestibule
Nasal Cavity and Paranasal Sinuses
Staging
Treatment
Nasal Vestibule
Nasal Cavity
Maxillary Sinus
Ethmoid Sinus
Sphenoid Sinus
Results of Treatment
Nasal Vestibule
Nasal Cavity and Ethmoid Sinus
Maxillary Sinus
Complications of Treatment
Surgery
Radiation Therapy
PARAGANGLIOMAS
Anatomy
Pathology
Patterns of Spread
Staging
Treatment
Selection of Treatment Modality
Management of Recurrence
Results of Treatment
Complications of Treatment
Surgery
Irradiation
MAJOR SALIVARY GLANDS
Anatomy
Pathology
Benign Tumors
Malignant Tumors
Patterns of Spread
Benign Mixed Tumors
Malignant Tumors
Lymphatic Spread
Clinical Picture
Parotid Gland
Sublingual Gland
Differential Diagnosis
Parotid Gland
Submandibular Gland
Biopsy Technique
Staging
Treatment
Selection of Treatment Modality
Surgical Treatment
Radiation Therapy
Chemotherapy for Salivary Gland Cancers
Results of Treatment
Parotid Gland
Submandibular Gland
Chemotherapy Results
Complications of Treatment
Surgery
Radiation Therapy
MINOR SALIVARY GLANDS
Anatomy
Pathology
Patterns of Spread
Clinical Picture
Treatment
Selection of Treatment Modality
Surgical Treatment
Irradiation Technique
Results of Treatment
46 Rehabilitation After Treatment of Head and Neck Cancer
Introduction
Pretreatment Counseling
Support during Treatment and Rehabilitation of the Chemoradiation Patient
Posttreatment Swallowing Assessment
Posttreatment Swallowing Rehabilitation
Posttreatment Speech Assessment
Rehabilitation of the Neck
Rehabilitation of the Oral Cavity
Rehabilitation After Partial Laryngeal Procedures
Rehabilitation After Laryngectomy or Laryngopharyngectomy
Resources for Rehabilitation of Head and Neck Cancer Patients
Section 2 Cancer of the Thoracic Cavity
47 The Molecular Biology of Lung Cancer
Introduction
Genomics: Tools for Identification, Prediction, and Prognosis
Somatic Landscape of Lung Cancer
Characterization of Aberrant Pathways
Transcriptome Profiling
Proteomic Approaches
Lessons Learned and Future Directions
Functional Genomics in Lung Cancer
Genome-wide RNA-Based and shRNA-Based Screening
CRISPR-Cas9 Gene Editing
Preclinical Model Systems for Studying Lung Cancer
Genetic and Epigenetic Alterations in Lung Cancer
EGFR/HER2/MET Signaling
RAS/RAF/MAPK Pathway
Pl3K/AKT/mTOR Pathway
Insulin Growth Factor Pathway
Fibroblast Growth Factor Pathway
The p53 Pathway
The p16INK4a-RB Pathway
Fusion Proteins
Epigenetic Changes in Lung Carcinogenesis
Metastasis and the Tumor Microenvironment
Epithelial-to-Mesenchymal Transition
Angiogenesis
Immune Checkpoint Inhibition
Exosomes as a Source of Information on Tumor Molecular Alterations
Lung Cancers Stem Cells
Telomerase-Mediated Cellular Immortality in Lung Cancer
Clinical Translation of Molecular Data
Current Translation of Rationale-based Targeted Therapy
Potential for Future Clinical Translation
48 Non–small-cell Lung Cancer
Introduction
Incidence and Etiology
Smoking
Genetic Predisposition
Occupational/Environmental
Anatomy and Pathology
Stage Classification
Histologic Classification
Genetic Characterization
Prognostic Factors
Screening and Prevention
Prevention
Screening
Diagnosis
Clinical Presentation
Diagnostic Approach
Stage Evaluation
General Approach
Extrathoracic Stage Evaluation
Mediastinal Stage Evaluation
Management by Stage
Overview of Lung Cancer Treatment Modalities
Preinvasive and Minimally Invasive Disease (Bronchial Intraepithelial Neoplasia, Adenocarcinoma In Situ, Ground Glass Nodules)
Stage I,II N0 Tumors (T1,2 N0)
Stage II N1-Positive Tumors (T1,2 N1)
Locally Invasive Tumors (T3,4 N0,1)
Stage III (N2,3)
Stage IV (M1)
Chemotherapy
Anti–Vascular Endothelial Growth Factor Therapy and Anti–Epidermal Growth Factor Receptor Antibodies
Special Clinical Situations
Oligometastases
Patients with Multiple Pulmonary Sites of Lung Cancer
Palliative Care
Role of Palliative Care
Specific Symptom Management
Conclusion
49 Small Cell and Neuroendocrine Tumors of the Lung
Introduction
Small Cell Lung Cancer
Incidence and Etiology
Anatomy and Pathology
Screening
Presentation and Diagnosis
Staging
Clinical and Serologic Predictive and Prognostic Factors
Management by Stage
Initial Management of Limited-Stage Small Cell Lung Cancer
Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer
Prophylactic Cranial Irradiation
Surgery in Early-Stage Small Cell Lung Cancer
Systemic Therapy
Summary and Recommendations for Initial Management of Small Cell Lung Cancer
Treatment of Relapsed Small Cell Lung Cancer
Recent Early-Phase Clinical Trials in Relapsed Small Cell Lung Cancer
Additional Research Efforts in Small Cell Lung Cancer
Molecular Characterization of Small Cell Lung Cancer: Genomic, Proteomic, and Epigenetic Studies
Clinical Evaluation of Therapeutic Targets
Role of Chemotherapy and Radiation Therapy to the Neuraxis
Palliative Care
Typical Carcinoid and Atypical Carcinoid Tumors
Incidence and Etiology
Anatomy and Pathology
Genetics
Screening
Diagnosis, Presentation, and Imaging
Staging
Management by Stage
Large Cell Neuroendocrine Carcinoma
Incidence and Etiology
Anatomy and Pathology
Genetics
Diagnosis/Presentation
Staging
Management by Stage
Treatment of Relapsed Large Cell Neuroendocrine Carcinoma
50 Neoplasms of the Mediastinum
Thymic Neoplasms
Incidence and Etiology
Anatomy and Pathology
Thymoma
Thymic Carcinoma
Diagnosis
Symptoms and Signs
Radiographic Imaging Studies
Serology and Chemistry
Invasive Diagnostic Tests
Management by Stage
Results of Treatment
Germ Cell Tumors
Incidence and Etiology
Anatomy and Pathology
Nonseminomatous Tumors
Diagnosis
Management by Histology
Prognosis
Nuclear Protein in Testis Midline Carcinoma
Section 3 Cancers of the Gastrointestinal Tract
51 Molecular Biology of the Esophagus and Stomach
Introduction
Molecular Biology of Esophageal Cancer
Epidermal Growth Factor Receptor
Cyclin D1 and p16INK4a
TP53 Tumor Suppressor Genes
Telomerase Activation
Tumor Invasion and Metastasis
Models of Esophageal Squamous Cell Cancer and Esophageal Adenocarcinoma
Functional Genomics
Molecular Biology of Gastric Cancer
Inherited Susceptibility
Role of Helicobacter pylori Infection and Other Host–Environmental Factors
Molecular Genetic Alterations
Models of Gastric Cancer
52 Cancer of the Esophagus
Introduction
Epidemiology
Etiologic Factors and Predisposing Conditions
Tobacco and Alcohol Use
Diet and Nutrition
Socioeconomic Status
Obesity
Physical Activity
Gastroesophageal Reflux Disease
Helicobacter pylori Infection
Barrett Esophagus
Tylosis
Plummer–Vinson/Paterson–Kelly Syndrome
Caustic Injury
Achalasia
Human Papillomavirus Infection
Prior Aerodigestive Tract Malignancy
Applied Anatomy and Histology
Anatomy
Histology
Natural History and Patterns of Failure
Clinical Presentation
Diagnostic Studies and Pretreatment Staging Tools
Staging Guidelines
Treatment
Treatment of Premalignant and T1 Disease
Treatment of Localized Disease (.T2, Nany, M0)
Predictors of Treatment Response
Predictors of Response to Chemoradiation
Palliation of Esophageal Cancer with Radiation Therapy
Palliation of Dysphagia and Bleeding
Treatment in the Setting of Tracheoesophageal Fistula
Radiotherapy Techniques
Radiation Therapy Planning and Technical Considerations
Acute and Long-Term Toxicity of Radiation Therapy
Treatment of Metastatic Disease
Single-Agent and Combination Chemotherapy
Targeted Agents and Immunotherapy
Stage-Directed Treatment Recommendations
53 Cancer of the Stomach
Introduction
Anatomic Considerations
Pathology and Tumor Biology
Histopathology
Molecular Classification of Gastric Cancer
Patterns of Spread
Clinical Presentation and Pretreatment Evaluation
Signs and Symptoms
Screening
Pretreatment Staging
Tumor Markers
Endoscopy
Computed Tomography
Magnetic Resonance Imaging
Positron Emission Tomography
Staging Laparoscopy and Peritoneal Cytology
Staging, Classification, and Prognosis
American Joint Committee on Cancer/International Union Against Cancer Tumor, Node, Metastasis Staging
Japanese Staging System
Classification of Esophagogastric Junction Cancers
Resection Classification
Gastric Cancer Nomograms: Predicting Individual Patient Prognosis after Potentially Curative Resection
Treatment of Localized Disease
Stage I Disease (Early Gastric Cancer)
Stage II and Stage III Disease
Technical Treatment-Related Issues
Surgery
Radiation Treatment
Treatment of Advanced Disease (Stage IV)
Treatment of Advanced Gastric Cancer: Palliative Systemic Chemotherapy
Second-line Therapy
Targeted Therapy
Surgery in Treatment of Metastatic Gastric Cancer
Surgery for Palliation
Role of Radiation in Palliation of Gastric Cancer
Gastric Cancer in the Elderly
54 The Molecular Biology of Pancreas Cancer
Introduction
Common Genetic Changes in Pancreatic Ductal Adenocarcinoma
Less-Prevalent Genetic Changes in Pancreatic Ductal Adenocarcinoma
Other Neoplastic Lesions
55 Cancer of the Pancreas
Incidence and Etiology
Epidemiology
Anatomy and Pathology
Exocrine Pancreatic Cancers
Pancreatic Ductal Adenocarcinoma
Less Common Pancreatic Cancers
Endocrine Pancreatic Cancers
Pancreatic Ductal Adenocarcinoma: Screening
Pancreatic Ductal Adenocarcinoma: Diagnosis
Pancreatic Ductal Adenocarcinoma: Staging
Stages I and II: Localized Pancreatic Ductal Adenocarcinoma
Surgical Anatomy
Assessing Resectability
Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma
Surgery
International Study Group of Pancreatic Surgery Contributions
Surgical Trials
Operative and Surgical Pathology Reporting
Assessing Prognosis
Adjuvant Therapy
Future Questions and Ongoing Adjuvant Trials
Surveillance Postresection
Stage III: Locally Advanced Disease
AJCC Staging versus “Intent of Management Based” Staging
Basic Management Considerations
Locally and Regionally Unresectable Disease
Evolution of Management for Local Regional Unresectable Disease
Management of Borderline Resectable Patients
Emerging Role of Stereotactic Body Radiotherapy
Stage IV: Metastatic Disease
Gemcitabine as a Gold Standard Therapy for Metastatic Pancreatic Adenocarcinoma
Fifteen Years of Failed Attempts to Move Beyond Gemcitabine Monotherapy
Modest Breakthroughs in the Treatment of Advanced Pancreatic Cancer
Monitoring Treatment Response
Symptom Palliation
Promising New Therapies on the Horizon
Future Directions and Challenges
Conclusion
56 Molecular Biology of Liver Cancer
Introduction
Genetic Alterations in Liver Cancer
Epigenetic Alterations in Liver Cancer
Mutational Landscape of Genetic Alterations—the Next Generation
The Microenvironment of Liver Cancer
Classification and Prognostic Prediction of Hepatocellular Carcinoma
Molecular Basis of Cholangiocarcinoma
Conclusion and Perspective
57 Cancer of the Liver
Introduction
Epidemiology
Etiologic Factors
Viral Hepatitis and Hepatocellular Carcinoma
Alcohol-Induced Hepatocarcinogenesis
Nonalcoholic Fatty Liver Disease
Other Etiologic Considerations
Chemical Carcinogens
Diagnosis
Staging
Treatment of Hepatocellular Carcinoma
Surgical Resection for Hepatocellular Carcinoma
Allogeneic Liver Transplantation for Hepatocellular Carcinoma
Adjuvant and Neoadjuvant Therapy
Adjuvant Therapy
Neoadjuvant Therapy
Treatment of Hepatitis C Before or After Treatment of Cancer
Choice of Resection, Ablation, or Transplantation
Ablative Therapy for Localized Hepatocellular Cancer
Embolic Therapies for Regional Disease
Radiation Therapy as Local Ablation for Hepatocellular Carcinoma
External-Beam Radiotherapy
Vaccine Therapy
Systemic Therapy for Hepatocellular Carcinoma
Treatment of Other Primary Liver Tumors
Fibrolamellar Hepatocellular Carcinoma
Hepatoblastoma
Epithelioid Hemangioendothelioma
58 Cancer of the Biliary Tree
Introduction
Anatomy of the Biliary Tract
Cholangiocarcinoma
Nomenclature of Cholangiocarcinoma
Etiology of Cholangiocarcinoma
Pathology of Cholangiocarcinomas
Intrahepatic Cholangiocarcinoma
Perihilar Cholangiocarcinoma
Distal Cholangiocarcinoma
Gallbladder Cancer
Incidence and Etiology
Risk Factors
Pathology
Prevention
Diagnosis
Staging
Management
Acknowledgments
59 Small Bowel Cancer
Introduction
Epidemiology
Pathogenesis and Risk Factors
Clinical Features
Diagnosis and Workup
Biochemical Investigations and Tumor Markers
Radiographic Studies
Small Bowel Adenocarcinoma
Incidence and Etiology
Anatomy and Pathology
Screening
Staging and Prognosis
Management
Carcinoid Tumors
Incidence and Etiology
Anatomy and Pathology
Diagnosis
Staging and Prognosis
Management
Small Bowel Lymphoma
Incidence and Etiology
Diagnosis
Staging and Prognosis
Treatment
Gastrointestinal Stromal Tumor
Metastatic Cancer to the Small Bowel
60 Gastrointestinal Stromal Tumor
Introduction
Incidence and Etiology
Anatomy and Pathology
Screening
Diagnosis
Staging
Management by Stage
Palliative Care
61 Molecular Biology of Colorectal Cancer
Introduction
Multistep Models of Colorectal Cancer and Genetic Instability
Mutational and Epigenetic Landscapes in Colorectal Cancer
Insights from Mouse Intestinal Crypts and Human Colorectal Cancers Lead to a Coherent Model for Colorectal Cancer Initiation and Progression
WNT Signaling
Other Growth Factor Pathways
Inherited Syndromes of Increased Cancer Risk Highlight Early Events and Critical Pathways in Colorectal Tumorigenesis
Familial Adenomatous Polyposis and the Central Importance of WNT Signaling
Hereditary Nonpolyposis Colorectal Cancer and the Role of DNA Mismatch Repair
Other Inherited Syndromes with Elevated Colorectal Cancer Risk
Familial Juvenile Polyposis
Insights from Mendelian Syndromes, Genome-Wide Association Studies, and the Microbiome
Oncogene and Tumor Suppressor Gene Mutations in Colorectal Cancer Progression
The KRAS, BRAF, and PIK3CA Oncogenes
MYC, CDK8, and Control of Cell Growth and Metabolism
TP53 and Other Tumor Suppressors
Prognostic and Predictive Value of Tumor Genotypes and Molecular Properties
62 Cancer of the Colon
Introduction
Epidemiology
Incidence and Mortality
Geographic Variation
Emigration Patterns in Population Groups
Race and Ethnicity
Socioeconomic Factors
Anatomic Shift
Etiology: Genetic, Environmental, and Other Risk Factors
Inherited Predisposition
Environmental Factors
Diet
Lifestyle
Drugs
Statins
Biomarkers
Human Papillomavirus
Escherichia coli
Familial Colorectal Cancer
Familial Adenomatous Polyposis
Hamartomatous Polyposis Syndromes
Anatomy of the Colon
Diagnosis of Colorectal Cancer
Screening for Colorectal Cancer
Staging and Prognosis of Colorectal Cancer
Staging
Prognosis
Category III Factors
Approaches to Surgical Resection of Colon Cancer
Colonoscopic Resection of Polyps
Anatomic Resection
Total Abdominal Colectomy
Complete Mesocolic Excision
Surgical Management of Complications from Primary Colon Cancer
Laparoscopic Colon Resection
Polyps and Stage I Colon Cancer
Stage II and Stage III Colon Cancer
Adjuvant Chemotherapy Considerations
Large-Scale Randomized Trials
Oral Fluoropyrimidine Therapies
Combination Adjuvant Therapies
Treatment of Stage II Patients
Impact of Microsatellite Instability on Treatment in Stage II and III Colon Cancer
Other Molecular Markers
Treatment Options for Stage III Patients
Timing of Treatment
Investigational Adjuvant Approaches
Portal Vein Infusion
Follow-up after Management of Colon Cancer with Curative Intent
Surgical Management of Stage IV Disease
Management of Unresectable Metastatic Disease
Fluorouracil
Capecitabine
Irinotecan
Irinotecan in First-line Combination Regimens
Oxaliplatin
Duration of Therapy
Combination versus Single-Agent Cytotoxic Chemotherapy
Toxicity
Bevacizumab Beyond Progression
Aflibercept
Ramucirumab
RAS and Other Determinants of Anti–Epidermal Growth Factor Receptor Resistance
Toxicities of Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies
First-line Epidermal Growth Factor Receptor versus Vascular Endothelial Growth Factor
Bevacizumab plus Anti–Epidermal Growth Factor Receptor Agents
Other Novel Agents
Molecular Predictive Markers
63 Cancer of the Rectum
Introduction
Anatomy
Lymphatic Drainage
Bowel Function
Autonomic Nerves
Staging
Surgery
Stage I
Stages II and III Rectal Cancer
Total Mesorectal Resection
Lateral Lymph Node Dissection
Resection of Contiguous Organs and Total Pelvic Exenteration
Combined Modality Therapy (Stage II and III)
Does Adjuvant Radiation Therapy Impact Survival?
Preoperative Radiation Therapy
Which Patients Should Receive Adjuvant Therapy?
Support of Nonoperative Management
Total Neoadjuvant Therapy
Concurrent Chemotherapy
Synchronous Rectal Primary and Metastases
Management of Unresectable Primary and Locally Advanced Disease (T4)
Management of Locally Recurrent Disease
Reirradiation in Recurrent Disease
Radiation Therapy Technique
Radiation Fields
64 Cancer of the Anal Region
Introduction
Epidemiology and Etiology
Human Papillomavirus Infection
HIV Infection
Other Risk Factors
Screening and Prevention
Pathology
Clinical Presentation and Staging
Prognostic Factors
Clinical
Molecular
Treatment of Localized Squamous Cell Carcinoma
Surgery
Definitive Chemoradiotherapy
Novel Biologic Radiosensitizing Agents
Follow-up Management
Treatment for HIV Population
Salvage Therapy for Persistent Disease or Local Recurrence
Management of Metastatic Disease
Treatment of Other Sites and Pathologies
Squamous Cell Carcinoma of the Anal Margin
Anal Canal Adenocarcinoma
Melanoma of the Anorectal Region
Section 4 Cancers of the Genitourinary System
65 Molecular Biology of Kidney Cancer
Introduction
Clear Cell Renal Cell Carcinoma
von Hippel-Lindau Disease
Papillary Renal Cell Carcinoma
Hereditary Papillary Renal Carcinoma: Type 1 Papillary
Sporadic Type 1 Papillary Renal Cell Carcinoma
Xp11.2 Translocation Renal Cell Cancer
Hereditary Leiomyomatosis and Renal Cell Carcinoma: Type 2 Papillary
Sporadic Type 2 Papillary Renal Cell Carcinoma
Chromophobe Renal Cell Carcinoma
Birt-Hogg-Dubé Syndrome
Sporadic Chromophobe Renal Cell Carcinoma
Additional Types of Renal Cell Carcinoma
Tuberous Sclerosis Complex
Succinate Dehydrogenase–Associated Renal Cancer
Conclusion
66 Cancer of the Kidney
Introduction
Epidemiology, Demographics, and Risk Factors
Pathology of Renal Cell Carcinoma
Differential Diagnosis and Staging
Hereditary Kidney Cancer Syndromes, Genetics, and Molecular Biology
von Hippel-Lindau Disease
Hereditary Papillary Renal Cell Carcinoma
Birt-Hogg-Dubé Syndrome
Hereditary Leiomyomatosis Renal Cell Carcinoma
Treatment of Localized Renal Cell Carcinoma
Radical Nephrectomy for Renal Cell Carcinoma
Partial Nephrectomy for Renal Cell Carcinoma
Thermal Ablation of Renal Cell Carcinoma
Active Surveillance of Clinically Localized Renal Cell Carcinoma
Treatment of Locally Advanced Renal Cell Carcinoma
Surgery for Tumor Thrombus in the Inferior Vena Cava
Lymphadenectomy
Adjuvant Therapy for Renal Cell Carcinoma
Surgical Management of Advanced Renal Cell Carcinoma
Cytoreductive Nephrectomy
Surgical Management of Recurrent and Metastatic Disease
Systemic Therapy for Advanced Renal Cell Carcinoma
Prognostic Factors
Prognostic Schema
Predictive Markers
Systemic Therapy
Immunotherapy
Mammalian Target of Rapamycin–Targeted Therapy
Second-line Therapy
Current Status of Systemic Therapy in Metastatic Renal Cell Carcinoma
Conclusion and Future Directions
Acknowledgments
67 Molecular Biology of Bladder Cancer
Introduction
Mutational Landscape
Mutation Rates, Mutational Signatures, and Mutational Processes
FGFR3, PIK3CA, and RAS Genes
Telomerase Reverse Transcriptase Promoter
TP53, RB1, and CDKN2A
Genes Involved in Chromatin Modification and Architecture
STAG2
Alterations in DNA Repair Pathways
Structural Alterations to the Genome
Heterogeneity and Clonal Evolution
Molecular Subtypes
DNA-Based Subtypes
Transcriptome-Based Subtypes
Therapeutic Opportunities and Future Outlook
68 Cancer of the Bladder, Ureter, and Renal Pelvis
Introduction
Epidemiology
Screening and Early Detection
Pathology
Primary Tumors of the Bladder
Upper Tract Tumors
Molecular Tumor Markers
Cancer of the Bladder
Clinical Presentation and Staging
Treatment of Non–Muscle-Invasive Bladder Cancer (Ta, Tis, T1)
Treatment of Muscle-Invasive Disease
Systemic Chemotherapy with Radical Therapy
Combined Modality Treatment of Local–Regionally Advanced Disease
Quality of Life After Cystectomy or Bladder Preservation
Metastatic Bladder Cancer
Other Chemotherapy Regimens
Cancers of the Renal Pelvis and Ureter
Clinical Presentation, Diagnosis, and Staging
Surgical Treatment
Adjuvant and Neoadjuvant Therapy: Advanced Primary Tumors
Advanced Transitional Cell Carcinoma of the Upper Tract
69 The Molecular Biology of Prostate Cancer
Introduction
The Genomic Landscape of Prostate Cancer
The Molecular Subtypes of Primary Prostate Cancer
ETS Family Gene Fusions
Speckle-Type POZ Protein Mutations
Forkhead Box A1 Mutations
Serine Peptidase Inhibitor, Kazal Type 1 Overexpression
Isocitrate Dehydrogenase 1 Mutations
The Clonal Evolution of Lethal Metastatic Prostate Cancer
Genetic Basis of Prostate Cancer Heritability
Androgen Signaling in Prostate Cancer
Androgen Receptor Structure and Function
Androgen Receptor Action
Intratumoral Androgen Biosynthesis
Glucocorticoid Signaling in Treatment Resistance
Other Signaling Pathways in Prostate Cancer
Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway
Other Signaling Pathways in Prostate Cancer
Cell Cycle Aberrations
Neuroendocrine Prostate Cancer
Areas of Ongoing Research and Emerging Therapeutic Approaches
DNA Repair Pathway
Epigenetic Alterations
Conclusion
70 Cancer of the Prostate
Introduction
Incidence and Etiology
Incidence and Mortality
Risk Factors
Prevention
Anatomy and Pathology
Patterns of Spread
Histopathology
Diagnosis, Risk Assessment, and State Assignment
Signs and Symptoms
Digital Rectal Examination
Prostate-Specific Antigen and Related Biomarkers
Biopsy
Imaging for Diagnosis and Staging
Risk Assessment
Management by Clinical States
Clinically Localized Disease
Radiotherapy for Localized Prostate Cancer
Adjuvant Radiation Therapy for High-Risk Patients After Radical Prostatectomy
Advanced Prostate Cancer: Rising Prostate-Specific Antigen and Clinical Metastases—Noncastrate and Castrate
Palliation
Bone-Directed Therapy
Future Directions
71 Cancer of the Urethra and Penis
Introduction
Urethral Cancer in the Male
Incidence and Etiology
Anatomy and Pathology
Diagnosis
Staging
Management by Stage
Radiation and Multimodal Therapy
Urethral Cancer in the Female
Incidence and Etiology
Anatomy and Pathology
Diagnosis
Staging
Management by Stage
Penile Cancer
Incidence and Etiology
Anatomy and Pathology
Diagnosis
Staging
Treatment
Carcinoma In Situ (Tis)
Verrucous Carcinoma (Ta)
Invasive Penile Cancer (T1, T2, T3)
Locally Advanced Penile Cancer (T4)
Management of Regional Lymph Nodes
Clinically Node-Negative Disease (cN0)
Clinically Node-Positive Disease (cN1, cN2, or cN3)
Metastatic Disease (M1)
72 Cancer of the Testis
Introduction
Incidence and Epidemiology
Risk Factors
Initial Presentation and Management
Symptoms and Signs
Diagnosis
Histology
Seminoma
Nonseminomatous Histologies
Biology
Mechanism of Germ Cell Transformation
Pluripotency of Embryonal-Like Differentiation in Germ Cell Tumors
Familial Predisposition to Germ Cell Tumors
Cisplatin Sensitivity and Acquired Resistance in Adult Germ Cell Tumors
Immunohistochemical Markers
Staging
Patterns of Metastasis
Serum Tumor Markers
Clinical Staging
Pathologic Staging
Factors Affecting Outcome
Management of Clinical Stage I Disease
Seminoma
Nonseminomatous Germ Cell Tumor
Management of Clinical Stage II Disease (Low Tumor Burden)
Seminoma
Nonseminomatous Germ Cell Tumor (Low Tumor Burden)
Management of Stage II Disease with High Tumor Burden and Stage III Disease
Good Prognosis
Intermediate and Poor Prognosis
Management of Residual Mass
Management of Recurrent Disease
Conventional-Dose Chemotherapy
High-Dose Chemotherapy and Stem Cell Transplant
Second and Subsequent Relapse
Surgery After Salvage Chemotherapy
Late Recurrence Nonseminomatous Germ Cell Tumor
Treatment Sequelae
Cardiovascular Effects
Chemotherapy-Induced Neurotoxicity
Hypogonadism and Infertility
Ototoxicity
Psychosocial Functioning
Second Malignant Neoplasms
Long-term Follow-up
Midline Tumors of Uncertain Histogenesis
Other Testicular Tumors
Sex Cord/Gonadal Stromal Tumors
Mesothelioma
Adenocarcinoma of the Rete Testis
Epidermoid Cyst
Lymphoma
Metastatic Carcinoma
Section 5 Gynecologic Cancers
73 Molecular Biology of Gynecologic Cancers
Introduction
Ovarian Cancer
Origins of Epithelial Ovarian Cancer
Molecular Pathways to Ovarian Cancer
Ovarian Cancer Microenvironment, Metastases, and Angiogenesis
Epigenetics
Role of Specific Immune Responses and Immunotherapy
Immunotherapy Clinical Trials in Ovarian Cancer
Adoptive Cellular Transfer Therapy
Endometrial Cancer
Type I Cancers
Type II Endometrial Cancer
Cervix, Vaginal, and Vulvar Cancers
Role of Human Papillomavirus
Immune Evasion by Human Papillomavirus
Human Papillomavirus Vaccines
Adoptive T-Cell Therapy
74 Cancer of the Cervix, Vagina, and Vulva
Carcinoma of the Cervix
Epidemiology
Natural History and Pattern of Spread
Pathology
Clinical Manifestations
Diagnosis, Clinical Evaluation, and Staging
Prognostic Factors
Treatment
Radical and Modified Radical Hysterectomy
Radical Trachelectomy
Radiotherapy after Radical Hysterectomy
Definitive Radiotherapy
Irradiation Followed by Hysterectomy
Chemotherapy Followed by Radical Surgery
External-Beam Radiotherapy Technique
Intensity-Modulated Radiotherapy
Role of Para-Aortic Irradiation
Brachytherapy
Complications of Radiotherapy
Concurrent Chemoradiation
Neoadjuvant Chemotherapy with Radiotherapy
Systemic Treatments
Palliative Radiotherapy
Carcinoma of the Vagina
Epidemiology
Natural History and Pattern of Spread
Pathology
Diagnosis, Clinical Evaluation, and Staging
Prognostic Factors
Treatment
Radiotherapy Technique
Role of Chemotherapy
Carcinoma of the Vulva
Epidemiology
Pathology
Diagnosis and Clinical Evaluation
Natural History and Pattern of Spread
Prognostic Factors and Staging
Treatment
Treatment of the Vulva
Treatment of Regional Disease
Radiotherapy Technique
Chemoradiation in Locoregionally Advanced Disease
Treatment of Metastatic Disease
75 Cancer of the Uterine Body
Endometrial Carcinoma
Epidemiology
Natural History and Routes of Spread
Diagnosis and Pretherapy Evaluation
Pathology
Prognostic Factors
Staging
Treatment of Early-Stage (Stage I and II) Disease
Treatment of Stage III Disease
Treatment of Distant Recurrence
Treatment of Locally Recurrent Disease
Carcinosarcoma (Mixed Müllerian Tumors)
Uterine Sarcomas
Uterine Leiomyosarcoma
Endometrial Stromal Sarcoma
76 Gestational Trophoblastic Neoplasia
Introduction
Incidence
Pathology and Natural History
Indications for Treatment
Following a Molar Pregnancy
Following a Nonmolar Pregnancy
Measurement of Human Chorionic Gonadotropin
Hyperglycosylated Human Chorionic Gonadotropin
Pretreatment Evaluation
Staging and Prognostic Score
Treatment
Low-Risk Disease
High-Risk Disease
Placental Site or Epithelioid Trophoblastic Tumors
Subsequent Pregnancy after Treatment for Gestational Trophoblastic Neoplasia
77 Ovarian Cancer
Incidence and Etiology
Etiology
Epidemiology
Anatomy and Pathology
Screening and Prevention
Cancer Antigen 125
The Risk of Ovarian Cancer Algorithm
Prevention of Ovarian Carcinoma
Diagnosis
The Adnexal Mass
Human Epididymis Protein 4
OVA1 and OVA2
Presentation and Evaluation of Advanced Disease
International Federation of Gynecology and Obstetrics Staging
Management by Stage
Early-Stage Epithelial Ovarian Cancer (FIGO Stage I)
Uncommon and Rare Tumors of the Ovary
Advanced-Stage Epithelial Ovarian Cancer (FIGO Stages II to IV)
Management of Newly Diagnosed Advanced-Stage Disease
Cytoreductive Surgery
Platinum-Taxane–Based Chemotherapy
Sequential Doublets and New Triplets
Neoadjuvant Chemotherapy
Intraperitoneal Chemotherapy
Hyperthermic Intraperitoneal Chemotherapy
Dose-Dense Paclitaxel
Maintenance Chemotherapy
Management of Recurrent Disease
The Concept of Platinum Sensitivity
Secondary Cytoreduction
Platinum-Based Doublets for Platinum-Sensitive Recurrent Disease
Nonplatinum Chemotherapeutic Options for Platinum-Resistant Recurrent Disease
EORTC 5595: Early versus Delayed Treatment of Recurrence
Antiangiogenesis Therapy
GOG 0218
OCEANS
AURELIA
Revisiting GOG 218 and ICON-7
PARP Inhibitors
Historical Notes
Clinical Implications of BRCA1/2 Mutation Status
Other Genes of Interest
PARP Inhibitors and Homologous Recombination Deficiency
Genomic Scars
Olaparib
Summary of Key Phase II Studies
Novel Combinations of Olaparib plus Antiangiogenesis Therapy
The SOLO Series
Rucaparib
ARIEL-3 and ARIEL-4
Niraparib
Switch Maintenance Therapy
Veliparib
Talazoparib
BRCA1/2 Reversion Mutations
Tolerability of PARP Inhibitors
Myelodysplastic Syndrome and Acute Myeloid Leukemia and Pneumonitis
Immunotherapy
Historical Notes
Therapeutic Vaccines
FANG Maintenance Autologous Tumor Cell Vaccine for Advanced Ovarian Cancer
Toll-Like Receptors
Oncolytic Viruses
Chimeric Antigen Receptors
Bispecific T-Cell Engagers
Immune-Mediated Toxicity
Immune-Related Response Criteria
Section 6 Cancer of the Breast
78 Molecular Biology of Breast Cancer
Introduction
Genetics of Breast Cancer
Hereditary Breast Cancer
Somatic Alterations in Breast Cancer
Copy Number Alterations in Breast Cancer
Transcriptional Profiles of Breast Cancer—Molecular Subtypes
Transcriptional Profiles of Breast Cancer—Prognosis and Benefit of Therapy
Epigenetics of Breast Cancer
Protein/Pathway Alterations
Estrogen Receptor Pathway
Growth Factor Receptor Pathways
Cyclin-Dependent Kinases
79 Malignant Tumors of the Breast
Incidence and Etiology
Risk Factors for Breast Cancer
Management of the High-Risk Patient
Anatomy and Pathology
Anatomy of the Breast
Lobular Carcinoma In Situ
Ductal Carcinoma In Situ
Pathology of Invasive Breast Cancer
Prognostic and Predictive Factors in Breast Cancer
Proliferation Markers
Molecular and Genomic Factors
Diagnosis and Biopsy
Staging
Management by Stage: Ductal Carcinoma In Situ
Treatment of the Breast
Treatment of the Axilla
Endocrine Therapy
Conclusions
Management by Stage: Primary Operable Invasive Breast Cancer
Overview
Breast-Conserving Therapy
Risk Factors for Locoregional Recurrence Following Conservative Surgery and Radiation Therapy
Preservation of a Cosmetically Acceptable Breast
Guidelines for Patient Selection for Breast Conservation
Conservative Surgery without Radiation Therapy
Hypofractionated Whole-Breast and Accelerated Partial-Breast Irradiation
Cardiotoxicity of Breast Radiotherapy
Preoperative Systemic Therapy for Operable Cancer
Mastectomy
Management of the Axilla
Postmastectomy Radiation Therapy
Management by Stage: Adjuvant Systemic Therapy
Adjuvant Endocrine Therapy
Adjuvant Chemotherapy
Adjuvant Therapy for HER2-Overexpressing Breast Cancer
Integration of Multimodality Primary Therapy
Follow-up for Breast Cancer Survivors
Management by Stage: Special Considerations
Paget Disease
Occult Primary with Axillary Metastases
Breast Cancer and Pregnancy
Male Breast Cancer
Phyllodes Tumor
Locally Advanced Breast Cancer and Inflammatory Breast Cancer
Fertility Preservation during Chemotherapy
Management of Locoregional Recurrence
Management by Stage: Metastatic Disease
Endocrine Therapy for Metastatic Breast Cancer
Chemotherapy for Metastatic Breast Cancer
Anti-HER2 Therapy for Metastatic Breast Cancer
Emerging Options for BRCA1- or BRCA2-Associated Breast Cancer
Immunotherapy in Advanced Breast Cancer
Treatment of Special Metastatic Sites in Patients with Breast Cancer
Section 7 Cancer of the Endocrine System
80 Molecular Biology of Endocrine Tumors
Endocrine Syndromes
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia Type 2
Multiple Endocrine Neoplasia Type 4
Carney Complex
Adrenal Gland
Cortisol-Producing Adenomas
Aldosterone-Producing Adenomas
Pheochromocytoma
Adrenocortical Carcinoma
Parathyroid Gland
Hyperparathyroidism–Jaw Tumor Syndrome
Familial Hypocalciuric Hypercalcemia
Neonatal Severe Hyperparathyroidism
Autosomal Dominant Hypoparathyroidism
Familial Isolated Hyperparathyroidism
Pituitary Gland
Familial Isolated Pituitary Adenoma
X-linked Acrogigantism
McCune-Albright Syndrome
Paraganglioma, Pheochromocytoma, and Pituitary Adenoma Association
Dicer1 Syndrome
Thyroid Gland
Follicular Adenomas
Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Papillary Thyroid Cancer
Follicular Thyroid Cancer
Hürthle Cell Carcinoma
Medullary Thyroid Cancer
Anaplastic Thyroid Cancer
Werner Syndrome
Acknowledgments
81 Thyroid Tumors
Anatomy and Physiology
Thyroid Nodules
Incidental 18F-Fluorodeoxyglucose Positron Emission Tomography–Positive Lesions
Malignancies of the Thyroid
Thyroid Tumor Classification and Staging Systems
Differentiated Thyroid Cancer
Incidence and Prognosis
Pathology
Treatment of Differentiated Thyroid Cancer
Surgery
Adjuvant Therapy
Papillary Thyroid Microcarcinoma
Long-Term Surveillance
Management of Local Recurrence and Distant Metastasis
Ultrasound-Guided Percutaneous Ethanol Ablation
Systemic Agents
Anaplastic Thyroid Carcinoma
Medullary Thyroid Cancer
Sporadic Medullary Thyroid Cancer
Familial Medullary Thyroid Cancer
Diagnosis and Staging of Medullary Thyroid Cancer
Prognosis of Medullary Thyroid Cancer
Treatment of Medullary Thyroid Cancer
Systemic Therapy in Medullary Thyroid Cancer
Thyroid Lymphoma
Children with Thyroid Carcinoma
Differentiated Thyroid Carcinoma
Medullary Thyroid Carcinoma
82 Parathyroid Tumors
Incidence and Etiology
Anatomy and Pathology
Clinical Manifestations and Screening
Diagnosis
Staging
Management of Parathyroid Cancer
Surgical Treatment
Radiotherapy
Chemotherapy
Other Treatment Modalities for Parathyroid Carcinoma
Follow-up and Natural History
Prognosis
83 Adrenal Tumors
Introduction
Incidence and Etiology
Incidence and Etiology of Adrenocortical Carcinoma
Incidence and Etiology of Pheochromocytoma
Anatomy and Pathology
Adrenal Gland Anatomy and Histology
Adrenal Tumor Pathology
Adrenal Tumor Molecular Pathology
Screening
Diagnosis
Initial Evaluation and Clinical Assessment of Adrenal Tumors
Laboratory Examinations and Hormonal Assessment
Imaging Exams
Other Tests
Staging
Management
Perioperative Hormonal Control of Adrenal Tumors (Benign Adrenocortical Tumor, Adrenocortical Carcinoma, Pheochromocytoma, and Paraganglioma—All American Joint Committee on Cancer Stages)
Management of Benign Adrenocortical Tumor and American Joint Committee on Cancer Stage I to III Pheochromocytoma and Paraganglioma
Management of American Joint Committee on Cancer Stage IV Pheochromocytoma and Paraganglioma
Management of American Joint Committee on Cancer/European Network for Study of Adrenal Tumors Stage I to III Adrenocortical Carcinoma
Management of AJCC/ENSAT Stage IV Adrenocortical Carcinoma
Palliative Care
Care for Patients with American Joint Committee on Cancer Stage IV Pheochromocytoma and Paraganglioma
Care for Patients with American Joint Committee on Cancer/European Network for Study of Adrenal Tumors Stage IV Adrenocortical Carcinoma or Unresectable Adrenocortical Carcinoma
84 Pancreatic Neuroendocrine Tumors
Introduction
Incidence and Etiology
Classification, Histopathology, and Molecular Genetics
Criteria for Pathologic Diagnosis
Grade—World Health Organization 2017, American Joint Committee on Cancer Eighth Edition, and Union for International Cancer Control
Tumor, Node, Metastasis
Molecular Genetics of Pancreatic Neuroendocrine Tumors
Diagnosis and Management of Pancreatic Neuroendocrine Tumors
Nonfunctional Tumors
Oncologic Management of Advanced Pancreatic Neuroendocrine Tumors
Systemic Therapy
Cytotoxic Chemotherapy
Streptozocin-Based Chemotherapy
Dacarbazine- and Temozolomide-Based Chemotherapy
Liver-Directed Regional Therapy
Therapeutic Strategy for Advanced Unresectable Pancreatic Neuroendocrine Tumors
Functional Tumors
Gastrinoma
Insulinoma
Rare Functional Endocrine Tumors
Additional Clinical Considerations
Hereditary Syndromes
High-Grade Neuroendocrine Carcinoma
Surgery Pitfalls
Small, Nonfunctioning, Sporadic Pancreatic Neuroendocrine Tumors
85 Carcinoid Tumors and the Carcinoid Syndrome
Incidence and Etiology
Anatomy and Pathology
Screening
General Principles of Neuroendocrine Tumor Diagnosis, Staging, and Management
General Diagnostic Principles
General Staging Principles
General Management Principles
Diagnosis, Staging, and Management by Primary Tumor Site
Thymic Neuroendocrine Tumors
Bronchial Neuroendocrine Tumors
Esophageal Neuroendocrine Tumors
Gastric Neuroendocrine Tumors
Small Bowel Neuroendocrine Tumors
Appendiceal Neuroendocrine Tumors
Colorectal Neuroendocrine Tumors
Diagnosis and Management of Carcinoid Syndrome
Antitumor Management
Somatostatin Analogs
Interferon-α
Mammalian Target of Rapamycin Inhibitors
Angiogenesis Inhibitors
Cytotoxic Chemotherapy
Management of Liver Metastases
Conclusions
86 Multiple Endocrine Neoplasia
Introduction
Multiple Endocrine Neoplasia Type
Incidence and Etiology
Molecular and Genetic Basis
Screening
Primary Hyperparathyroidism
Enteropancreatic Neuroendocrine Tumors
Pituitary Tumors
Less Common Tumors
Management of Metastatic Disease
Follow-up
Multiple Endocrine Neoplasia Types 2 and 3 and Familial Medullary Thyroid Cancer
Incidence and Etiology
Molecular Genetic Basis
Screening
Management of Metastatic Disease
Multiple Endocrine Neoplasia Type
Section 8 Sarcomas of Soft Tissue and Bone
87 Molecular Biology of Sarcomas
Introduction
Soft Tissue Sarcomas
Translocation-Associated Soft Tissue Sarcomas
Soft Tissue Sarcomas of Simple Karyotype Associated With Mutations
Complex Soft Tissue Sarcoma Types
Bone and Cartilaginous Tumors
Cartilaginous Tumors
Osteosarcoma
Future Directions: Next-Generation Sequencing and Functional Screens
88 Soft Tissue Sarcoma
Introduction
Incidence and Etiology
Epidemiology
Etiology and Risk Factors
Chemical Agents
Anatomic and Age Distribution and Pathology
Anatomic and Age Distribution
Pathologic Classification and Biological Potential
Clinical and Pathologic Features of Specific Soft Tissue Tumor Types
Fibroblastic and Myofibroblastic Tumors
So-called Fibrohistiocytic Tumors
Adipocytic Tumors
Smooth Muscle Tumors
Skeletal Muscle Tumors
Vascular Tumors
Perivascular Tumors
Neural Tumors
Extraskeletal Chondro-osseous Tumors
Tumors of Uncertain Differentiation
Undifferentiated or Unclassified Tumors
Histologic Grading
Diagnosis and Staging
Clinical Features
Differential Diagnosis
Imaging
Biopsy
Sarcoma Staging
Nomograms
Histologic and Prognostic Factors for Primary Extremity and Truncal Sarcoma
Diagnostic and Prognostic Factors for Primary Retroperitoneal or Intra-abdominal Sarcoma
Management by Presentation Status, Extent of Disease, and Anatomic Location
Management of Extremity and Truncal Sarcoma
Management of Primary Localized Retroperitoneal Sarcoma
Serious Complications of Primary Treatment
Management of Specific Histologic Subtypes and Sites
Palliative Care
Surgery
Palliative Radiation
Chemotherapy
Future Directions
89 Sarcomas of Bone
Introduction
Incidence and Etiology
Anatomy and Pathology
Screening
Diagnosis
History
Physical Examination
Diagnostic Studies
Staging
Management by Diagnosis and Stage
Systemic Therapies for Ewing Sarcoma
Systemic Therapies for Osteosarcoma
Surgical Therapies for Local Control of Sarcomas of Bone
Amputation Versus Limb Salvage
Amputation: Concepts and Specialized Techniques
Limb Salvage: Options and Recent Advances
Continuing Care: Surveillance and Palliation
Section 9 Cancers of the Skin
90 Cancer of the Skin
General Approach to Nonmelanoma Skin Cancer
Diagnosis of Nonmelanoma Skin Cancer
Management General Principles and Modalities
Basal Cell Carcinoma
Incidence and Etiology
Clinical and Pathologic Features
Staging, Prognosis, and Management
Squamous Cell Carcinoma and Actinic Keratosis
Incidence and Etiology
Clinical and Pathologic Features of Squamous Cell Carcinoma and Actinic Keratosis
Staging, Prognosis, and Management
Merkel Cell Carcinoma
Incidence and Etiology
Clinical and Pathologic Features
Staging, Prognosis, and Management
Dermatofibrosarcoma Protuberans
Incidence and Etiology
Clinical and Pathologic Features
Staging, Prognosis, and Management
Angiosarcoma
Incidence and Etiology
Clinical and Pathologic Features
Staging, Prognosis, and Management
Microcystic Adnexal Carcinoma
Incidence and Etiology
Clinical and Pathologic Features
Prognosis and Management
Sebaceous Carcinoma
Incidence and Etiology
Clinical and Pathologic Features
Prognosis and Management
Extramammary Paget Disease
Incidence and Etiology
Clinical and Pathologic Features
Prognosis and Management
Atypical Fibroxanthoma
Incidence and Etiology
Clinical and Pathologic Features
Prognosis and Management
91 Molecular Biology of Cutaneous Melanoma
Introduction
The Cancer Genome Atlas Effort in Cutaneous Melanoma
The RAS-RAF-MAPK Pathway
RAF Kinases
RAS Family GTPases
NF1
Additional Oncogenic Pathways
Cell Cycle Regulators
The p53 Pathway
The Phosphatidylinositol 3-Kinase Pathway
Receptor Tyrosine Kinases
RAC1
Telomerase
Triple Wild-Type Melanomas
Melanin Synthesis Pathway
MITF
The MC1R Pathway
Summary and Future Directions
92 Cutaneous Melanoma
Introduction
Molecular Biology of Melanoma
Mutational Landscape in Melanoma
Driver Mutations in Melanoma
Progression of Melanocytes to Cutaneous Melanoma
Epidemiology
Changes in Incidence
Sex and Age Distribution
Melanoma in Children, Infants, and Neonates
Anatomic Distribution
Etiology and Risk Factors
Ultraviolet Light Exposure
Physical Traits
Familial Predisposition
Pregnancy and Estrogen Use
Prevention and Screening
Sun Protection
Screening for Early Diagnosis
Testing for Genomic Changes in Melanoma
Diagnosis of Primary Melanoma
Characteristics of Primary Melanoma
Biopsy
Melanoma Subtypes: Histologic Growth Patterns
Prognostic Factors for Primary Melanomas
Unresolved Issues in Melanoma Staging
General Considerations in Clinical Management of a Newly Diagnosed Cutaneous Melanoma (Stages I and II)
Clinical Evaluation and Radiologic Studies for Patients with Clinical Stage I or II Melanoma
Wide Local Excision for Clinical Stage I or II Melanoma: General Considerations
Clinical Trials to Define Margins of Excision for Primary Cutaneous Melanomas
French and Swedish Cooperative Surgical Trials
Intergroup Melanoma Trial
British Cooperative Group Trial
Surgical Staging of Regional Nodes
Selection of Patients for Sentinel Node Biopsy
Sentinel Node Biopsy Subsequent to a Prior Wide Local Excision
Management
Clinically Localized Melanoma
Clinical Follow-up after Surgical Treatment
Thin Primary Melanoma (Clinical T1A)
Clinical T1B Melanomas
Clinical T2A, T2B Melanomas
Clinical T3A Melanomas (Clinical Stage IIA)
Clinical T3B Melanomas (Clinical Stage IIB)
Thick Melanomas (T4A, T4B, >4 mm Thick)
Special Considerations in Management of Primary Melanomas
Primary Melanomas of the Head and Neck
Primary Melanomas of the Mucous Membranes
Primary Melanomas of the Fingers and Toes
The Role of Radiation Therapy in the Management of Primary Melanoma Lesions
Clinical Follow-up for Intermediate-Thickness and Thick Melanomas (Stage IB to IIC)
Regionally Metastatic Melanoma (Stage III): Lymph Node Metastasis, Satellite Lesions, and In-Transit Metastases
Management of Local Recurrence
Management of Satellite and In-Transit Metastases
Intratumoral Therapies with Potential Systemic Effects
Management of Regional Lymph Node Metastases
Management of Patients after a Positive Sentinel Node Biopsy (Stage IIIA if Nonulcerated Primary Lesion, One to Three Positive Nodes)
Management of Palpable Metastatic Melanoma in Regional Nodes: Therapeutic or Completion Lymphadenectomy
Management of Regional Metastases in Patients with Visceral or Other Distant Disease
Melanoma Radiation Therapy
The Role of Radiation Therapy in the Management of Regional Nodal Disease
Adjuvant Systemic Therapy (Stages IIB, IIC, and III)
Adjuvant Interferon Therapy
Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) Blockade in Adjuvant Therapy
PD-1 Blockade in Adjuvant Therapy
BRAF Inhibitor–Based Adjuvant Therapy
Neoadjuvant Therapy for Resectable Stage III or IV Melanoma
Clinical Follow-up for Patients with Regionally Metastatic Melanomas (Stage III)
National and International Guidelines for Follow-up
Management of Distant Metastases of Melanoma (Stage IV)
Timing of Distant Metastases
Patterns of Metastases
Prognostic Factors in Distant Metastatic Melanoma (Stage IV)
Clinical Evaluation of Patients with Distant Metastasis (Stage IV)
Surgery for Distant Metastases (Stage IV)
Adjuvant Therapy for Resected Stage IV Melanoma
Treatment of Unresectable Metastatic (Stage IV) Melanoma
Radiation Therapy for Metastatic Melanoma (Stage IV)
The Role of Radiation Therapy in the Management of Distant Metastatic Disease
Radiation Therapy for Brain Metastases: Special Considerations
Current Radiation Research for Melanoma: Interactions with Immune Therapy
Section 10 Neoplasms of the Central Nervous System
93 Molecular Biology of Central Nervous System Tumors
Introduction
Pediatric Brain Tumors
Medulloblastoma
Low-Grade Glioma
High-Grade Glioma
Ependymal Tumors
Adult Brain Tumors
Low-Grade Glioma
High-Grade Glioma
Meningioma
Summary
Acknowledgments
94 Neoplasms of the Central Nervous System
Epidemiology of Brain Tumors
Incidence and Prevalence
Etiologic Factors
Environmental Factors
Viral Associations
Hereditary Syndromes
Classification
Anatomic Location and Clinical Considerations
Intracranial Tumors
Spinal Axis Tumors
Neurodiagnostic Tests
Magnetic Resonance Imaging
Neuraxis or Spinal Imaging
Supplementary Imaging Modalities
Pseudoresponse and Pseudoprogression
Cerebrospinal Fluid Examination
Surgery
Preoperative Considerations
Anesthesia and Positioning
General Surgical Principles
Radiation Therapy
General Concepts
Radiobiologic and Toxicity Considerations
Treatment Planning and Delivery Methods
Chemotherapy and Targeted Agents
The Blood–Brain Barrier
Challenges Specific for Targeted Agents
Other Systemic Therapy Considerations
Specific Central Nervous System Neoplasms
Cerebral Glioma
World Health Organization Grade I: Astrocytoma
World Health Organization Grade II: Low-Grade Glioma
World Health Organization Grade III: Anaplastic Astrocytoma
World Health Organization Grade III: Anaplastic Oligodendroglioma
World Health Organization Grade IV: Glioblastoma
Dose Escalation
Chemotherapy for Recurrent Glioblastoma
Gliomatosis Cerebri
Optic, Chiasmal, and Hypothalamic Gliomas
Clinical Considerations
Pathologic Considerations
Imaging Findings
Treatment Decision Making
Surgery
Radiation Therapy
Chemotherapy
Brain Stem Gliomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Cerebellar Astrocytomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Gangliogliomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Ependymoma
Clinical and Pathologic Features
Surgery
Radiation Therapy
Chemotherapy
Meningiomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Radiosurgery
Chemotherapy
Primitive Neuroectodermal or Embryonal Central Nervous System Neoplasms
Medulloblastoma
Pineal Region Tumors and Germ Cell Tumors
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Pituitary Adenomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Medical Therapy
Craniopharyngiomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Vestibular Schwannomas
Clinical and Pathologic Considerations
Treatment
Glomus Jugulare Tumors
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Radiosurgery
Hemangioblastomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Chordomas and Chondrosarcomas
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Radiosurgery
Particle Beam Therapy
Chemotherapy
Choroid Plexus Tumors
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Spinal Axis Tumors
Clinical and Pathologic Considerations
Surgery
Radiation Therapy
Chemotherapy
Section 11 Cancers in Adolescents and Young Adults
95 Adolescents and Young Adults with Cancer
Epidemiology
Etiology and Biology
Signs, Symptoms, and Delays in Diagnosis
Prevention and Screening
Diagnosis
Management
Surgery
Radiation Therapy
Chemotherapy
Psychosocial and Supportive Care
Oncofertility
Models of Care
Choice of Treatment Setting and Specialist
Lack of Participation in Clinical Trials
Progress
Survival for Adolescents and Young Adults Compared to Children (Age Younger Than 15 Years)
Survival for Adolescents and Young Adults Compared to Older Adults (Ages 40 to 69 Years)
Survival Trends
Cancer Mortality Worldwide
Death Rates and Trends by Site
Future Challenges
Section 12 Lymphomas in Adults
96 Molecular Biology of Lymphoma
Introduction
The Cell of Origin of Lymphoma
B-Cell Development and the Dynamics of the Germinal Center Reaction
T-Cell Development
General Mechanisms of Genetic Alterations in Lymphoma
Chromosomal Translocations
Aberrant Somatic Hypermutation
Copy Number Gains and Amplifications
Activating Point Mutations
Inactivating Mutations and Deletions
Infectious Agents
Molecular Pathogenesis of B-Cell Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Burkitt Lymphoma
Follicular Lymphoma
Diffuse Large B-Cell Lymphoma
Primary Mediastinal B-Cell Lymphoma
Marginal Zone Lymphoma
Chronic Lymphocytic Leukemia
Molecular Pathogenesis of T-Cell Non-Hodgkin Lymphoma
Adult T-Cell Leukemia/Lymphoma (HTLV-1 Positive)
Angioimmunoblastic T-Cell Lymphoma
Peripheral T-Cell Lymphoma Not Otherwise Specified
Cutaneous T-Cell Lymphoma
Anaplastic Large-Cell Lymphoma
Hepatosplenic T-Cell Lymphoma
Molecular Pathogenesis of Hodgkin Lymphoma
Cell of Origin
Genetic Lesions
97 Hodgkin Lymphoma
Introduction
Pathology of Hodgkin Lymphoma
Cell of Origin
Classical Hodgkin Lymphoma
Nodular Lymphocyte-Predominant Hodgkin Lymphoma
Early-Stage Hodgkin Lymphoma
Prognostic Features
Treatment
Advanced-Stage Hodgkin Lymphoma
Prognostic Factors
Treatment
Complications of Treatment
Special Circumstances
Elderly Patients
Pregnancy
Relapsed and Refractory Hodgkin Lymphoma
Immune Checkpoint Inhibitors
98 Non-Hodgkin Lymphoma
Introduction
Incidence and Etiology
Exposures and Diseases Associated with Non-Hodgkin Lymphoma
Biology and Pathology
Biologic Background for Classification of Lymphoid Neoplasms
B-cell Development
T-cell Development
Natural Killer Cells
Immunophenotyping of Lymphoid Cells
Chromosomal Translocations and Oncogene Rearrangements
Lymphoma Classification: the Principles of the World Health Organization Classification of Lymphoid Neoplasms
Categories of Lymphoid Neoplasms
Diagnosis, Staging, and Management
Differential Diagnosis and Sites of Disease at Presentation
Initial Management
Staging and Prognostic Systems
Specific Disease Entities
Precursor B- and T-cell Leukemia/Lymphoma
Follicular Lymphoma
Small Lymphocytic Lymphoma/B-cell Chronic Lymphocytic Leukemia
Lymphoplasmacytic Lymphoma
Marginal Zone Lymphomas
Nodal Marginal Zone Lymphomas
Splenic Marginal Zone Lymphoma
Extranodal Marginal Zone Lymphoma
Mantle Cell Lymphoma
Diffuse Large B-cell Lymphoma
Other Large B-cell Lymphomas
Special Situations
Primary Mediastinal Large B-cell Lymphoma
Grey Zone Lymphoma and High-Grade B-cell Lymphoma
Burkitt Lymphoma
Mature T-Cell and Natural Killer Cell Neoplasms
Mycosis Fungoides
Peripheral T-cell Lymphomas, Not Otherwise Specified
Angioimmunoblastic T-cell Lymphoma
Enteropathy-Associated T-cell Lymphoma and Monomorphic Epitheliotropic Intestinal T-cell Lymphoma
Anaplastic Large-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Subcutaneous Panniculitis-Like T-cell Lymphoma
Extranodal Natural Killer/T-cell Lymphomas, Nasal Type
Adult T-cell Leukemia/Lymphoma
Primary Central Nervous System Lymphoma
Central Nervous System Prophylaxis for Aggressive Lymphomas
Posttransplant Lymphoproliferative Disorders
HIV-associated Non-Hodgkin Lymphoma
99 Cutaneous Lymphomas
Introduction
Mycosis Fungoides and the Sézary Syndrome
Epidemiology and Etiology
Pathobiology
Diagnosis and Staging
The Sézary Syndrome
Staging and Prognosis of Mycosis Fungoides and the Sézary Syndrome
Clinical Evaluation of Patients with Cutaneous Lymphoma
Principles of Therapy of Mycosis Fungoides and the Sézary Syndrome
Skin-Directed Therapy
Topical Chemotherapies
Topical Bexarotene Gel
Phototherapy
Total Skin Electron-Beam Therapy
Combined and Sequential Therapy
Systemic Therapy for Mycosis Fungoides and the Sézary Syndrome
Biologic Therapies
Bexarotene (Retinoid Therapy)
Histone Deacetylase Inhibitors
Denileukin Diftitox
Monoclonal Antibodies
Cytotoxic Chemotherapy
Autologous and Allogeneic Bone Marrow Transplantation
Other Cutaneous Lymphomas
Primary CD301 Lymphoproliferative Disorders
Subcutaneous Panniculitis-like T-Cell Lymphoma and Cutaneous Peripheral T-Cell Lymphoma Unspecified
The Cutaneous Natural Killer Lymphomas
Cutaneous B-Cell Lymphoma
100 Primary Central Nervous System Lymphoma
Epidemiology
Histopathology and Molecular Profile
Diagnosis
Prognostic Models
Management of Newly Diagnosed Primary Central Nervous System Lymphoma
Treatment in the Elderly
Management of Refractory/Relapsed Primary Central Nervous System Lymphoma
Monitoring and Follow-up
Neurotoxicity
Section 13 Leukemias and Plasma Cell Tumors
101 Molecular Biology of Acute Leukemias
Introduction
Leukemic Stem Cell
Elucidation of Genetic Events in Acute Leukemia
Mutations Affecting Transcription Factors
Core-Binding Factor
Retinoic Acid Receptor Alpha Gene
HOX Family Members
C/EBPα
GATA Factors
Mutations that Result in Overexpression of c-MYC
Mutation of Lymphoid Development Factors in Acute Lymphoid Leukemia
Chromosomal Translocations Involving the T-cell Receptor
RBM15/MKL1
Mutations of Epigenetic Modifiers
KMT2A (aka MLL) Translocations
MOZ and TIF2
TET2
DNMT3A
ASXL1
EZH2
Mutations Affecting Signaling
Oncogenic RAS Mutations
Activating Mutations in Tyrosine Kinases and Associated Receptors
Mutations in Tumor Suppressor Genes
WT1
TP53
Activating Mutations of NOTCH
Mutations Altering Localization of NPM1
Mutations in Cohesin Complex Genes
Mutations in Splicing Machinery
Mutational Complementation Groups in Acute Leukemias
Conclusion
102 Management of Acute Leukemias
Introduction
Acute Myeloid Leukemia
Diagnosis and Prognostic Evaluation in Acute Myeloid Leukemia
Treatment of Newly Diagnosed Patients with Acute Myeloid Leukemia
General Recommendations for Therapy
Acute Promyelocytic Leukemia
Treatment of Relapsed Disease
Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Epidemiology
Diagnosis and Evaluation
Cytogenetic and Molecular Abnormalities
Therapy for Acute Lymphoblastic Leukemia
Treatment of Specific Acute Lymphoblastic Leukemia Subgroups
103 Molecular Biology of Chronic Leukemias
Introduction
Chronic Myeloid Leukemia
Pathogenesis
Molecular Anatomy of the BCR-ABL1 Junction
Functional Domains of BCR-ABL1 and Kinase Activation
Signal Transduction
Chronic Myeloid Leukemia Stem Cells
Progression to Blastic Phase
Chronic Myeloid Leukemia Bone Marrow Microenvironment
Conclusions
Chronic Lymphocytic Leukemia
Origin of Chronic Lymphocytic Leukemia
Chromosomal Abnormalities in the Pathogenesis of Chronic Lymphocytic Leukemia
Recurrent Mutations in Chronic Lymphocytic Leukemia
Progression of Chronic Lymphocytic Leukemia: The Role of Genomic Instability and Clonal Evolution
Chronic Lymphocytic Leukemia and Proliferation
Chronic Lymphocytic Leukemia and Disrupted Apoptosis
B-cell Receptor Signaling in Chronic Lymphocytic Leukemia
Conclusion
Acknowledgments
104 Chronic Myeloid Leukemia
Introduction
Epidemiology and Pathogenesis
Diagnosis
Laboratory Tests
Differential Diagnosis and Staging
Disease Stages
Prognostic Factors
Therapy
Imatinib
Dasatinib
Nilotinib
Bosutinib
Ponatinib
Assessment of Response to Tyrosine-Kinase Inhibitors
Therapy of Chronic Phase Chronic Myeloid Leukemia
First-line Treatment
Cytogenetic Analysis
Long-term Monitoring
Comparison of Different Tyrosine-Kinase Inhibitors When Used as First-line Treatment
Second-line Treatment
Treatment of Advanced Disease
Bone Marrow Transplantation
Future Directions
Logistical Aspects of Chronic Myeloid Leukemia Care
Pregnancy
Treatment Discontinuation
New Molecules
Acknowledgments
105 Chronic Lymphocytic Leukemias
Introduction
Immunophenotype
Molecular Biology
Immunoglobulin Heavy Chain Variable Gene Mutation Status
Molecular Abnormalities
Immune Abnormalities
Diagnosis
International Workshop on Chronic Lymphocytic Leukemia Revised Diagnostic Criteria
Clinical Manifestations
Laboratory Findings
Autoimmune Complications
Staging
Indications for Treatment and Response Criteria
Indications for Treatment
Assessment of Response
Treatments for Chronic Lymphocytic Leukemia
Chemotherapy
Monoclonal Antibodies
Chemoimmunotherapy
Eliminating Minimal Residual Disease
CD20 Monoclonal Antibody Maintenance Postchemoimmunotherapy
B-Cell Signaling Pathway Inhibitors for Treatment of Chronic Lymphocytic Leukemia
Bcl-2 Inhibitor
Immune Modulatory Agents
Cellular Therapy for CLL
Management Recommendations
First-line Treatment Recommendations
Relapsed/Refractory Chronic Lymphocytic Leukemia Treatment Recommendations
Splenectomy
Therapeutic Considerations for Specific Problems in Patients with Chronic Lymphocytic Leukemia
Second Malignancies and Transformation
Prolymphocytic Leukemia
Large Granular Lymphocyte Leukemia
Hairy Cell Leukemia
Treatments for Hairy Cell Leukemia
Treatments for Relapsed Hairy Cell Leukemia
106 Myelodysplastic Syndromes
Introduction
Historical Perspective
Epidemiology
Etiology
Pathology
The French-American-British Classification
The World Health Organization Classification
Pathogenesis
Dysregulation of Immunity as a Driver in Myelodysplastic Syndromes
The 5q2 Syndrome
Clinical Presentation
Risk Assessment and Prognosis
The International Prognostic Scoring System
The Revised International Prognostic Scoring System
The Global MD Anderson Scoring System
Management of Myelodysplastic Syndromes
Erythropoiesis-Stimulating Agents
Lenalidomide
Azanucleosides
Immunosuppressive Therapy
Allogeneic Hematopoietic Cell Transplantation
Iron Chelation Therapy
Benefit of Deferasirox in Myelodysplastic Syndromes
How Do I Treat Myelodysplastic Syndrome Patients?
107 Plasma Cell Neoplasms
Introduction
Multiple Myeloma
Disease Definition
Incidence and Prevalence
Pathogenesis
Establishment of Premalignant Clone
Progression of Premalignancy to Multiple Myeloma
Pathogenesis of Multiple Myeloma Bone Disease
Cytogenetic Classification
Clinical Features
Diagnostic Tests
Standard Laboratory tests
Differential Diagnosis
Staging and Risk Stratification
Prognosis
Treatment
Active Drugs in Myeloma
Treatment of Newly Diagnosed Multiple Myeloma
Stem Cell Transplantation
Maintenance Therapy
Treatment of Relapsed Multiple Myeloma
Treatment of Plasma Cell Leukemia
Supportive Care
Bone Disease
Anemia
Infections
Hypercalcemia
Renal Failure
Hyperviscosity Syndrome
MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE
Introduction
Incidence and Prevalence
Clinical Features
Differential Diagnosis
Prognosis
Risk Stratification
Management
SMOLDERING MULTIPLE MYELOMA
Introduction
Prevalence
Clinical Features
Differential Diagnosis
Prognosis
Risk Stratification
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
Section 14 Other Cancers
108 Cancer of Unknown Primary
Introduction
Pathology Evaluation
Accuracy of Immunohistochemical Staining
Additional Pathologic Diagnostic Tests in Cancers of Unknown Primary
Gene Expression–Based Tissue of Origin Testing/Molecular Tumor Profiling
Summary
Use of Next-Generation Sequencing
Summary
Clinical Features and Evaluation
Clinical Evaluation
Treatment
Chemotherapy
Targeted Therapy
Prognostic Factors
109 Benign and Malignant Mesothelioma
Introduction
Epidemiology
Mechanism of Asbestos Carcinogenesis
Animal Models of Asbestos Carcinogenicity
Asbestos Carcinogenicity in Humans
Mechanism of Asbestos Pathogenicity
Overview of Molecular Mechanisms in Mesothelioma
Cytogenetic Assessment of Malignant Mesotheliomas
Alterations of Specific Tumor Suppressor Genes in Mesothelioma
Simian Virus 40
Radiation and Mesothelioma
Genetic Predisposition to Mesothelioma: BAP1
Pathology of Mesothelioma
Benign Mesotheliomas
Malignant Mesothelioma
Clinical Presentation
Symptoms
Physical Examination
Laboratory Examination and Blood Biomarkers
Radiologic Examination
Diagnostic Approach for Presumed Mesothelioma
Thoracentesis and Closed Pleural Biopsy
Thoracoscopy
Natural History
Prognostic Indicators
Staging
Treatment
Overview
Supportive Care
Surgery for Pleural Mesothelioma
Palliation or Macroscopic Complete Resection
Controversy Regarding Performance of Extrapleural Pneumonectomy
Evolution of Lung-Sparing Approaches for Macroscopic Complete Resection
Chemotherapy
First-line Chemotherapy
Second-line Chemotherapy
Novel Therapeutic Approaches
Angiogenesis Inhibition
Immunotherapy
Mesothelin-Directed Therapy
Radiotherapy for Mesothelioma
The Role of Radiotherapy
Combined Chemotherapy and Definitive Radiotherapy
Combined Surgical Resection and Adjuvant Radiotherapy
Radiation Before Extrapleural Pneumonectomy
Radiation After Lung Sparing
Prevention of Scar Recurrences
Palliation Using Radiotherapy
Proton Beam Radiation
110 Peritoneal Metastases and Peritoneal Mesothelioma
Introduction
Natural History Studies Document the Importance of Local-Regional Progression
Patient Selection Using Quantitative Prognostic Indicators
Biologic Aggressiveness as Measured by Histopathology for Epithelial Appendiceal Neoplasms and Peritoneal Mesothelioma
Extent of Disease as Measured by the Peritoneal Cancer Index at the Time of Abdominal-Pelvic Exploration
The Completeness of Cytoreduction Score Performed after the Resection
Preoperative Radiologic Imaging by Computed Tomography
Tumor, Node, Metastasis Stage; Peritoneal Cytology; and Clinical Features of the Primary Cancer
Pharmacokinetic Advantage of Perioperative Chemotherapy
Appendiceal Malignancy
Natural History
Histologic Classification
Outcome of Treatment of Peritoneal Dissemination by Cytoreductive Surgery Followed by Hyperthermic Perioperative Chemotherapy
Surgical Learning Curve
Colorectal Peritoneal Metastases: Curative Treatment and Prevention
Incidence
Results
Prevention of Peritoneal Metastases
Malignant Peritoneal Mesothelioma
Clinical Presentation and Diagnosis
Treatment and Results
Gastric Cancer
Treatment and Prevention of Peritoneal Metastases
Natural History and Palliative Treatment
Curative Treatment: Cytoreductive Surgery and Hyperthermic Perioperative Chemotherapy
Prevention of Gastric Cancer Peritoneal Metastases
Peritoneal Metastases in Ovarian Cancer
Cytoreductive Surgery and Intraperitoneal Chemotherapy in Epithelial Ovarian Cancer
Sarcomatosis
111 Intraocular Melanoma
Introduction
Incidence and Etiology
Anatomy and Pathology
Histology
Iris Melanoma
Ciliary Body Melanoma
Choroidal Melanoma
Extrascleral Extension
Ophthalmic Diagnosis
The Finger MOST Mnemonic
Ophthalmic Examination
Ophthalmic Photography and Angiography
Ophthalmic Ultrasound Imaging
Intraocular Tumor Biopsy
Staging
Universal Uveal Melanoma Staging
Management of Primary Uveal Melanoma
The Collaborative Ocular Melanoma Study
Overview: Treatment of Uveal Melanoma
Small T1 Uveal Melanomas
Intermediate T2 Uveal Melanoma
Large T3 and T4 Uveal Melanomas
Episcleral Radiation Therapy
Proton Beam Radiation
Treatment for Special Cases
Iris and Iridociliary Melanoma
Choroidal Melanomas that Touch or Surround the Optic Disc
Extrascleral Tumor Extension
Radiation Retinopathy and Optic Neuropathy
Diagnosis of Metastasis
The Incidence of Metastasis
History and Physical
Metastatic Workup
Adjuvant Therapy for High-Risk Uveal Melanoma
Management of Metastatic Disease
Liver-Directed Therapy
Systemic Therapy
Immunotherapy
Clinical Trials for High-Risk and Metastatic Uveal Melanoma
Biomarkers: Prognostic and Predictive Factors
Clinical Prognostic Factors
Diffuse Growth Pattern
Histopathologic, Physiologic, Genetic, and Molecular Prognostic Factors
Summary
Section 15 Oncologic Emergencies
112 Superior Vena Cava Syndrome
Introduction
Anatomy and Pathophysiology
Clinical Presentation and Etiology
Diagnostic Workup
Disease-Specific Management and Outcomes
Small-cell Lung Cancer
Non–small-cell Lung Cancer
Non-Hodgkin Lymphoma
Nonmalignant Causes
Catheter-Induced Obstruction
Treatment
Radiation Therapy
Endovascular Stenting and Angioplasty
Surgery
Areas of Uncertainty
Recommendations
113 Increased Intracranial Pressure
Introduction
Pathophysiologic Considerations
Epidemiology and Pathogenesis
Increase in Cerebral Parenchymal Pressure and Cerebrospinal Fluid Flow Obstruction
Disorders Affecting Cerebrospinal Fluid Production or Reabsorption
Venous Outflow Obstructions
Clinical Presentation
Diagnosis
Treatment
114 Spinal Cord Compression
Incidence and Etiology
Anatomy and Pathophysiology
Clinical Presentation
Differential Diagnosis
Diagnosis
Grading
Management by Stage
Step 1: Histologic Diagnosis
Step 2: Initiation of Corticosteroids
Step 3: Evaluate Life Expectancy, Performance Status, Extent of Disease, and Systemic Treatment Options
Step 4: MNOP Algorithm for Managing Malignant Spinal Cord Compression
115 Metabolic Emergencies
Introduction
Tumor Lysis Syndrome and Hyperuricemia
Definition, Diagnosis, and Staging
Incidence and Etiology
Pathogenesis
Screening
Management
Management by Stage
Hyponatremia
Incidence and Etiology
Screening, Diagnosis, and Management
Hypercalcemia
Incidence, Etiology, and Diagnosis
Management
Lactic Acidosis
Hyperammonemia
Incidence, Etiology, and Diagnosis
Management
Summary
Section 16 Treatment of Metastatic Cancer
116 Metastatic Cancer to the Brain
Introduction
Epidemiology
Clinical Presentation
Imaging and Diagnosis
Prognosis
Symptom Management
Corticosteroids
Anticonvulsants
Venous Thromboembolism
Treatment Options
Whole-Brain Radiotherapy
Prophylactic Cranial Irradiation
Surgery
Whole-Brain Radiotherapy with or without Surgery
Surgery with or without Whole-Brain Radiotherapy
Stereotactic Radiosurgery
Stereotactic Radiosurgery versus Surgery
Whole-Brain Radiotherapy with or without Stereotactic Radiosurgery
Stereotactic Radiosurgery with or without Whole-Brain Radiotherapy
Stereotactic Radiosurgery to Resection Cavity
Salvage Therapy
Chemotherapy and Targeted Therapies
Leptomeningeal Metastases
Epidemiology
Clinical Presentation
Diagnosis
Radiation Therapy
Intra–Cerebrospinal Fluid Chemotherapy
Systemic Chemotherapy and Other Agents
117 Metastatic Cancer to the Lung
Introduction
Presentation and Diagnosis of Pulmonary Metastases
Surgical Metastasectomy
Criteria for Surgical Resection
Open versus Minimally Invasive Surgery
Approach to Open Metastasectomy
Role of Lymph Node Dissection
Extent of Resection
Ablative Therapies
Radiofrequency and Microwave Ablation
Stereotactic Body Radiation Therapy
Treatment Concerns and Outcomes for Individual Histologies
Soft Tissue and Osteogenic Sarcoma
Melanoma
Renal Cell Carcinoma
Breast Cancer
Germ Cell Tumors
Colorectal Cancer
Conclusion
118 Metastatic Cancer to the Liver
Introduction
Relevant Hepatic Physiology
Hepatic Anatomic Nomenclature
Hepatic Imaging
Hepatic Resection
Thermal Ablation
Stereotactic Body Radiation Therapy
Portal Vein Embolization
Two-Stage Hepatectomy
Transarterial Therapy
Selective Internal Radiation Therapy
Palliative Whole-Liver Radiation Therapy
Hepatic Colorectal Adenocarcinoma Metastases
Introduction
Hepatic Resection
Extrahepatic Disease
Thermal Ablation
Adjuvant and Perioperative Chemotherapy
Neoadjuvant Chemotherapy
Conversion to Resectability
Biologic Agents
Chemotherapy-Associated Hepatotoxicity
Hepatic Artery Infusional Chemotherapy
The “Disappearing Metastasis”
Prognostic Factors
Stereotactic Body Radiation Therapy
Selective Internal Radiation Therapy
Hepatic Neuroendocrine Carcinoma Metastases
Introduction
Hepatic Resection
Systemic Chemotherapy
Transarterial Therapy
Prognostic Factors
Selective Internal Radiation Therapy
Noncolorectal Nonneuroendocrine Hepatic Metastases
Introduction
Ocular (Uveal) Melanoma
Breast Carcinoma
Sarcoma
119 Metastatic Cancer to the Bone
Introduction
Presentation
Pathophysiology
Diagnostic Evaluation
Therapeutic Modalities
Systemic Therapy
Bisphosphonates for Metastatic Bone Disease
Oral Bisphosphonates
Intravenous Bisphosphonates
Denosumab
Optimum Use of Bone-Targeted Agents in Metastatic Bone Disease
New Targeted Therapies in the Treatment of Metastatic Bone Disease
External-Beam Radiation Therapy
Wide-Field or Half-Body External-Beam Radiation
Reirradiation
Systemic Radionuclides
Controlling Side Effects of Treatment
Radiotherapy for Complications of Bone Metastases: Localized External-Beam Radiotherapy for Pathologic Fractures
Pathologic and Impending Fractures
Stereotactic Body Radiotherapy of Spinal Metastases
Lower Extremity
Preoperative Embolization of Bone Metastases
Upper Extremity
Spine
120 Malignant Pleural and Pericardial Effusions
Malignant Pleural Effusions
Clinical Presentation
Diagnosis and Evaluation
Treatment
Video-Assisted Thoracoscopic Surgery Partial Pleurectomy and Mechanical Pleurodesis
Decortication
Treatment Algorithm
Malignant Pericardial Effusions
Clinical Presentation
Diagnosis and Evaluation
Treatment
Summary
121 Malignant Ascites
Incidence and Etiology
Anatomy and Pathology
Ascitic Fluid Homeostasis
Pathophysiology of Malignant Ascites
Diagnosis
Management
Traditional Therapy
Regional Treatments
Steroids and Radioisotopes
Novel Therapies: Cytokines, Infectious Agents, and Immunotherapy
122 Paraneoplastic Syndromes
Introduction
Paraneoplastic Neurologic Syndromes
Diagnosis
Classical Syndromes
Treatment
Paraneoplastic Endocrinology Syndromes
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Vasopressin Receptor Antagonists (Vaptans)
Ectopic Cushing Syndrome
Hypoglycemia
Paraneoplastic Hematologic Syndromes
Anemia
Polycythemia
Leukocytosis
Thrombocytosis
Paraneoplastic Dermatologic Manifestations
Acanthosis Nigricans
Tripe Palms
Sign of Leser-Trélat
Erythema Gyratum Repens
Necrolytic Migratory Erythema
Bazex Syndrome
Paraneoplastic Pemphigus
Hypertrichosis Lanuginose
Paraneoplastic Rheumatologic Manifestations
Hypertrophic Osteoarthropathy
Vasculitis
Idiopathic Inflammatory Myopathies
Section 17 Stem Cell Transplantation
123 Autologous Hematopoietic Cell Transplantation
Introduction
Autologous Hematopoietic Progenitor Cell Collection
Autologous Hematopoietic Cell Transplantation Toxicities and Supportive Care
Indications for Autologous Hematopoietic Cell Transplantation
Autologous Hematopoietic Cell Transplantation for Plasma Cell Myeloma
Autologous Hematopoietic Cell Transplantation for Myeloma: The Pre–Novel Agent Era
Autologous Hematopoietic Cell Transplantation for Myeloma: The Modern Era
Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Myeloma
Older Patients and Those with Comorbidities
Maintenance Therapy after Hematopoietic Cell Transplantation
Tandem Autologous Hematopoietic Cell Transplantation
Response and Minimal Residual Disease after HCT
Unique Considerations for Hematopoietic Progenitor Cell Collection in Myeloma
Salvage Second or Third Transplants at Relapse
Future Directions in Autologous Hematopoietic Cell Transplantation for Myeloma
Autologous Hematopoietic Cell Transplantation for Rare Plasma Cell Dyscrasias
Autologous Hematopoietic Cell Transplantation for Lymphomas
Conventional and Novel Conditioning Regimens
Disease-Specific Indications for Hematopoietic Cell Transplantation in Lymphomas
Hematopoietic Cell Transplantation for Follicular Lymphoma
First Remission
Relapsed Disease
Hematopoietic Cell Transplantation for Transformed Follicular Lymphoma
Hematopoietic Cell Transplantation for Mantle Cell Lymphoma
Hematopoietic Cell Transplantation for Waldenström Macroglobulinemia
Hematopoietic Cell Transplantation for Marginal Zone and Small Lymphocytic Lymphoma
Hematopoietic Cell Transplantation for Diffuse Large B-Cell Lymphoma
In First Remission for High-Risk Disease
In Relapsed Disease
Hematopoietic Cell Transplantation for Burkitt Lymphoma
Hematopoietic Cell Transplantation for Hodgkin Lymphoma
Relapsed Hodgkin Lymphoma
Primary Refractory Hodgkin Lymphoma
Hematopoietic Cell Transplantation for T-Cell Lymphomas
Unique Considerations for Hematopoietic Cell Transplantation Mobilization in Lymphomas
Tumor Cell Contamination in Autograft
Posttransplantation Maintenance Therapies for Lymphoid Malignancies
Functional Imaging and Autologous Hematopoietic Cell Transplantation Outcomes
Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
Autologous Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia
Autologous Hematopoietic Cell Transplantation for Germ Cell Tumors
Late Complications after Autologous Hematopoietic Cell Transplantation
124 Allogeneic Stem Cell Transplantation
Introduction
Conditioning Regimens
Myeloablative Conditioning
Reduced-Intensity Conditioning
Radiolabeled Monoclonal Antibodies
Stem Cell Sources
Human Leukocyte Antigen–Matched Donors
Unrelated Donors
Umbilical Cord Blood
Mismatched and Haploidentical Donors
Immunobiology of Allogeneic Hematopoietic Cell Transplantation
Graft-versus-host Disease
Graft versus Leukemia
Complications of Allogeneic Hematopoietic Cell Transplantation and Their Management
Acute and Chronic Graft-versus-host Disease
Infectious Complications
Bacterial Infections
Clostridium difficile
Fungal and Pneumocystis jirovecii Infection
Herpesvirus Infections
Other Viral Infections
Organ Complications
Early and Late Pulmonary Complications
Hepatic Complications
Renal Complications
Graft Failure
Outcome of Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies and Solid Tumors
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia
Other Lymphoid Malignancies
Chronic Myelogenous Leukemia
Solid Tumors
Management of Posttransplant Relapse
Future Directions
Section 18 Management of Adverse Effects of Treatment
125 Infections in the Cancer Patient
RISK FACTORS FOR INFECTIONS IN PATIENTS WITH CANCER AND ANTIMICROBIAL PROPHYLAXIS
Risk Factors for Infection
Intrinsic Host Factors
Treatment-Related Factors
Immunomodulatory Agents and Infectious Risk
Prevention of Infections
Prevention of Bacterial Infections
Prevention of Fungal Infections
Prevention of Pneumocystis jirovecii Pneumonia
Prophylaxis of Viral Infections
DIAGNOSIS AND MANAGEMENT OF INFECTIOUS DISEASES SYNDROMES
Fever and Neutropenia
Risk Stratification
Neutropenic Fever Syndromes
Fungal Infections in Patients with Cancer
Immune Augmentation
Catheter-Related Infections and Bacteremia
Skin Lesions and Soft Tissue Infections
Respiratory Tract Infections
Pulmonary Infiltrates
Epstein-Barr Virus–Induced Posttransplant Lymphoproliferative Disease
Gastrointestinal Tract and Abdominal Infections
Surgical Intra-abdominal Infections
Central Nervous System Infections
Genitourinary Infections
Multidrug-Resistant Organisms of Interest in Oncology
Multidrug-Resistant Gram-Positive Bacteria
Multidrug-Resistant Gram-Negative Bacteria
126 Neutropenia and Thrombocytopenia
Introduction
Hematopoiesis
Neutropenia and Its Management
Management of Neutropenia
127 Nausea and Vomiting
Introduction
Nausea and Vomiting Syndromes
Pathophysiology of Treatment-Induced Nausea and Vomiting
Defining the Risk of Nausea and Vomiting
Antiemetic Agents
Highest Therapeutic Index
Lower Therapeutic Index
Antiemetic Treatment by Clinical Setting
Highly Emetogenic Chemotherapy
Moderately Emetogenic Chemotherapy
Low and Minimally Emetogenic Chemotherapy
Special Chemotherapy-Induced Nausea and Vomiting Problems
Radiotherapy-Induced Nausea and Vomiting
128 Diarrhea and Constipation
Introduction
Diarrhea
Definition
Chemotherapy-Induced Diarrhea
Neutropenic Colitis
Clinical Presentation
Pathogenesis
Diagnostic Investigations
Diagnostic Criteria
Ischemic Colitis (Nonneutropenic Enterocolitis)
Targeted Therapy–Associated Diarrhea
Immunotherapy-Associated Diarrhea
Radiotherapy-Induced Diarrhea
Other Causes of Treatment-Related Diarrhea
Clostridium difficile Diarrhea
Enteral Feeding
Celiac Plexus Block
Assessment
General Principles in the Management of Diarrhea
Antidiarrhea Medications
Opioids
Somatostatin Analogs
Uridine Triacetate
Other Agents
Specific Management Guidelines
Chemotherapy-Induced Diarrhea
Radiation Therapy–Induced Diarrhea
Immunotherapy-Induced Diarrhea and Colitis
Management of Neutropenic Enterocolitis
Diarrhea Prophylaxis
Prevention of Radiation Diarrhea
Prevention of Chemotherapy Diarrhea
Constipation
Definition
Prevalence
Treatment-Related Causes
Differential Diagnosis
Diagnosis
Investigation
General Measures
Laxatives
Opioid Antagonists for Opioid-Induced Constipation
Enemas and Suppositories
Managing Fecal Impaction
Conclusion
129 Oral Complications
Introduction
Oral Mucositis
Chemotherapy-Induced Mucositis
Radiation-Induced Mucositis
Radiation Therapy–Related Complications
Pathogenesis of Chemotherapy- and Radiation Therapy–Induced Oral Mucositis
Chronic Graft-Versus-Host Disease Oral Manifestations
Sequelae of Oral Complications
Oropharyngeal Pain
Xerostomia
Strategies for Prevention and Treatment of Oral Complications
Pretherapy Dental Evaluation and Intervention
Assessment of the Oral Mucosa
Treatment Strategies
Radioprotectors
Vitamins and Other Antioxidants
Amifostine
Glutamine
Anti-Inflammatory Agents
Biologic Response Modifiers
Epidermal Growth Factors
Hematopoietic Growth Factors
Keratinocyte Growth Factors
Antimicrobials
Cryotherapy
Laser
Miscellaneous Agents
Treatment for Oral Chronic Graft-Versus-Host Disease
Symptom Management
Oropharyngeal Pain
Sucralfate
Gelclair
Anesthetic Cocktails
Doxepin
Opioids
Xerostomia
130 Pulmonary Toxicity
Introduction
Radiation-Induced Pulmonary Toxicity
Mechanisms of Lung Injury and Histology
Patient Considerations
Clinical Features
Diagnosis
Treatment
Chemotherapy-Induced Pulmonary Toxicity
Mechanism of Pulmonary Injury and Histopathology
Clinical Features
Diagnosis
Treatment
Additional Resources
131 Cardiac Toxicity
Introduction
Chemotherapeutics
Anthracyclines
Cyclophosphamide
Ifosfamide
Taxanes (Paclitaxel and Docetaxel)
Fluoropyrimidines
Monoclonal Antibodies
Bevacizumab
Radiotherapy-Associated Cardiac Sequelae
Pericardial Disease
Myocardial Dysfunction
Valvular Disease
Electrical Abnormalities
Coronary Heart Disease
Conclusion
132 Hair Loss and Other Hair Changes
Introduction
Anatomy and Physiology of Hair
Classification of Hair Loss
Diagnosis of Hair Loss
Treatment and Prevention of Chemotherapy-Induced Hair Loss
Radiation-Induced Hair Changes
Other Hair-Associated Changes
Future Considerations
133 Gonadal Dysfunction
Introduction
Effects of Cytotoxic Agents on Adult Men
Biologic Considerations
Characteristics of Gonadal Toxicity
Individual Drugs
Radiation Therapy
Combination Regimens
Effects of Cytotoxic Agents on Adult Women
Biologic Considerations
Characteristics of Gonadal Toxicity
Individual Drugs
Radiation Therapy
Combination Regimens
Effects of Cytotoxic Agents on Children
Extent of Gonadal Toxicity in Boys
Extent of Gonadal Toxicity in Girls
Gonadal Dysfunction after Cranial Irradiation
Preservation of Fertility, Hormone Levels, and Sexual Function
Choice of Regimens
Gonadal Shielding and Oophoropexy
Sperm Cryopreservation
Optimization of Fertility After Treatment
Assisted Reproductive Technologies
Female Germ Cell Cryopreservation and Development
Immature Male Germ Cell Cryopreservation and Development
Pharmacologic Attempts at Preserving Fertility in Men
Pharmacologic Attempts at Preserving Fertility in Women
Fertility Preservation in Women with Cervical Cancer
Genetic Concerns
Biologic Considerations
Pregnancy Outcome
Gamete Genomic Analysis
Acknowledgments
134 Fatigue
Introduction
Definition, Risk Factors, and Mechanisms of Cancer-Related Fatigue
Screening and Evaluation of the Patient with Cancer-Related Fatigue
Interventions for Cancer-Related Fatigue
Pharmacologic Interventions
Nonpharmacologic Interventions
Exercise, Physical Activity, and Structured Rehabilitation
Management of Concurrent Symptoms
Psychoeducational Interventions
Interventions to Improve Sleep Quality and Circadian Rhythmicity
Complementary and Integrative Therapies
Summary
135 Second Cancers
Introduction
Carcinogenicity of Individual Treatment Modalities
Radiation Therapy
Chemotherapy
Genetic Susceptibility to Second Primary Cancers
Monogenic and Multigenic Disease Models
Gene–Exposure and Gene–Gene Interactions
Hypothesis-Generating Genome-Wide Association Studies
Preemptive Pharmacogenomics and Preemptive Radiogenomics
Risk of Second Malignancy in Patient with Selected Primary Cancers
Lymphoma
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Selected Second Primary Cancers After Hodgkin Lymphoma or Non-Hodgkin Lymphoma
Breast Cancer
Testicular Cancer
Prevention and Risk Reduction for Second Primary Cancers
Pediatric Malignancies
Influence of Primary Cancer
Host-Related Risk Factors
Radiation
Chemotherapy
Multiple Subsequent Cancers in Long-term Childhood Cancer Survivors
Secondary Breast Cancer
Secondary Thyroid Cancer
Secondary Osteosarcoma and Soft Tissue Sarcoma
Secondary Central Nervous System Tumors
Secondary Melanoma and Nonmelanoma Skin Cancer
Other Secondary Carcinomas
Genetic Conditions
Comment
136 Neurocognitive Effects
Introduction
Assessment of Cognitive Function
Neurocognitive Effects of Central Nervous System Tumors and Treatment
Impact of Tumor
Impact of Treatment
Neurocognitive Effects in Non–Central Nervous System Cancer
Cancer-Related Cognitive Impairment
Chemotherapy
Treatment of Cognitive Dysfunction
Conclusion
137 Cancer Survivorship
Introduction
Definition of Survivorship and Scope of the Problem
Goals of Survivorship Health Care
Identifying Late Effects of Cancer Therapy
Surveillance and Guidelines for Late Effects
Interventions to Prevent Potential Late Effects
Promotion of Adjustment and Healthy Lifestyles
Care Plans
Delivery of Follow-up Care and Best Practice Models
Educational Considerations
Enhancing Research
Survivorship Advocacy
Employment
Insurance
Advocacy
Conclusion
Part VI: Palliative and Alternative Care
Section 1 Supportive Care and Quality of Life
138 Management of Cancer Pain
Introduction
Epidemiology
Definition of Pain
Types of Pain
Somatic Pain
Visceral Pain
Neuropathic Pain
Temporal Aspects of Pain
Acute Pain
Chronic Pain
Intensity of Pain
Measurement Schemas
Brief Pain Inventory
McGill Pain Questionnaire
Patient-Reported Outcome Measures
Memorial Symptom Assessment Scale
Functional Assessment of Cancer Therapy–General
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30
Edmonton Symptom Assessment Scale
Common Pain Syndromes
Clinical Assessment of Pain
Take a Careful History of the Patient’s Pain Complaint
Evaluate the Patient’s Psychological State
Perform Careful Medical and Neurologic Examinations
Order the Appropriate Diagnostic Studies and Personally Review the Results
Treat the Pain to Facilitate the Appropriate Workup
Reassess the Patient’s Response to Therapy
Individualize the Diagnostic and Therapeutic Approaches
Discuss Goals of Care and Consider Specialist Palliative Care Consultation
Management of Cancer Pain
Pharmacologic Management of Cancer Pain
Analgesic Drug Therapy: The Mainstay of Cancer Pain Management
The World Health Organization Cancer Pain Guidelines
Cancer Pain Management Using the World Health Organization Three-Step Analgesic Ladder
Adjuvant Drugs
Adjuvants to Enhance Analgesia
Adjuvant Analgesics for Neuropathic Pain
Antidepressants
Anticonvulsants
Local Anesthetics
Cutaneous Local Anesthetics
Corticosteroids
Other Adjuvant Drugs
Adjuvant Drugs for Bone Pain
Adjuvants to Treat Side Effects
Psychological Approaches
Anesthetic and Neurosurgical Approaches
Local Anesthetics
Peripheral Nerve Block
Celiac Plexus Block
Lumbar Sympathetic Block
Stellate Ganglion Block
Neuropharmacologic Approaches
Epidural and Interspinal Approach
Neuroablative and Neurostimulatory Procedures for the Relief of Pain
Trigger Point Injection and Acupuncture
Physiatric Approaches
Algorithm for Cancer Pain Management
Future Directions
Acknowledgments
139 Nutrition Support
Background
Causes of Malnutrition in Cancer Patients
Cancer Cachexia Syndrome
Energetics
Intermediary Metabolism
Cytokines and Hormones
Nutrition Screening and Assessment
Pharmacotherapy of Cancer-Associated Weight Loss and Malnutrition
Nutrition Support of Cancer Patients
Optimal Route of Administration of Nutrition Support
Optimal Timing for Initiation of Nutrition Support
Prescribing Nutritional Support
Enteral Nutrition
Parenteral Nutrition
Specialty Nutrition Formulas: Immune-Enhancing Formulas and Formulas for Organ Failure
Effect of Nutrition Support on Tumor Growth
Glycemic Control in Patients with Cancer
Palliative Nutrition Support in Patients Not Receiving Anticancer Treatment
140 Sexual Problems
Introduction
Cancer in Men
Prostate
Testicular
Cancers that Affect Men and Women
Bladder
Head and Neck
Blood, Bone Marrow, and Lymphatic System
Colorectal
Cancer in Women
Breast
Gynecologic Cancers
BRCA Mutation Carriers
Cancer in Children and Young Adults
Relevant Sociocultural Considerations
Special Considerations for Male Patients
Special Considerations for Female Patients
Disruption of Intimacy and Relational Considerations
Communication About Sexual Problems
Asking About Sexual Problems
Use of Validated Assessment Tools
Intervention
141 Psychological Issues
Introduction
Common Psychiatric Conditions
Screening for Psychological Problems
Coping
Treatment Interventions
Psychosocial
Psychoeducational Interventions
Outcome
Implications for Cancer Progression and Mortality
Psychotropic Medication
Antidepressants
Tamoxifen and Selective Serotonin Reuptake Inhibitors
Antianxiety Agents
Antipsychotics
Conclusion
142 Communicating News to the Cancer Patient
Introduction
Preventing Illness
Communication
Explanations
Uncomfortable Questions
Information
Meaning
Cafeteria Explanations
143 Specialized Care of the Terminally Ill
Introduction
Early Specialist Palliative Care
Communication
Specific Problems in the Setting of Advanced Cancer
Dyspnea
Malignant Bowel Obstruction
Malignant Biliary Obstruction
Gastric Outlet Obstruction
Malignant Ascites
Wounds
Impending Death
Preparing the Family for the Dying Process
Conclusions
144 Rehabilitation of the Cancer Patient
Introduction
The Rehabilitation Team
Physiatrist
Therapists and Allied Rehabilitation Clinicians
Complications of Cancer and Its Treatment
Direct Effects of Cancer
Systemic Therapy
Radiotherapy
Surgery
Other Medical Disorders
Neuromuscular Complications of Cancer and Cancer Treatment
Brain Dysfunction
Spinal Cord Dysfunction
Peripheral Nervous System Dysfunction
Myopathy
Evaluation of Neuromuscular Disorders
Treatment of Neuromuscular Disorders
Musculoskeletal Complications of Cancer and Cancer Treatment
Bony Metastases
Radiation Fibrosis Syndrome
Radiation Fibrosis Syndrome in Hodgkin Lymphoma
Head and Neck Cancer
Lymphedema
Rehabilitation Interventions
Therapeutic Exercise
Therapeutic Modalities
Section 2 Complementary, Alternative, and Integrative Therapies
145 Complementary, Alternative, and Integrative Therapies in Cancer Care
Background
Definitions
Prevalence
Establishing an Integrative Oncology Approach with Patients
Integrative Oncology Model
Physical Well-being
Psychosocial Well-being: the Mind–Body Connection
Patient–Clinician Communication Regarding Complementary and Integrative Medicine
Safety Concerns
Standardization and Quality
Specific Complementary and Integrative Medicine Therapies
Biologically Based Therapies Used for Cancer Treatment and Secondary Prevention
Nonbiologically Based Therapies
INDEX
An aparitie | 2018 |
Autor | Vincent T. DeVita Jr. MD, Steven A. Rosenberg, Theodore S. Lawrence |
Dimensiuni | 22.1 x 7.1 x 28.2 cm |
Editura | LWW |
Format | Hardback |
ISBN | 9781496394637 |
Limba | Engleza |
Nr pag | 2432 |
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