DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology
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DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology

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Cod produs/ISBN: 9781496394637

Disponibilitate: Acest produs nu este momentan in stoc

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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