DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology / Edition 9

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Overview


DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology has been acclaimed by the worldwide medical community as the standard-setting oncology reference. Its primary goal is to present the practicing oncologist with the practical as well as cutting-edge information needed to ensure the best possible care for each individual patient. The hallmark of this book from its inception and a major reason it has gained worldwide acceptance as the definitive source of cancer information has been its approach to the treatment of cancer patients by stage of presentation with a tightly coordinated description of the role of each treatment modality in the care of individual patients. To ensure a balance multidisciplinary approach, a surgeon, a medical oncologist, and a radiation oncologist author each of the major treatment chapters. Each of the major treatment sections is preceded by an updated, brief chapter describing the molecular biology of that cancer and the prospects this new information holds for the improved management of cancer patients. Greater emphasis has been given in recent editions to the increasing importance of molecular biology and cancer screening and prevention, as well as palliative care, supportive oncology and quality of life issues.
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Product Details

  • ISBN-13: 9781451105452
  • Publisher: Lippincott Williams & Wilkins
  • Publication date: 5/16/2011
  • Edition description: Ninth, North American Edition
  • Edition number: 9
  • Pages: 2800
  • Sales rank: 489,175
  • Product dimensions: 8.70 (w) x 11.10 (h) x 2.80 (d)

Table of Contents


Contributing Authors vii

Preface xxvii

Acknowledgments xxix

PART ONE

MOLECULAR BIOLOGY OF CANCER

1.

The Cancer Genome . . . . . . . . . . . . . . . . . . . 2Yardena Samuels, Alberto Bardelli, and Carlos López-Otín

Cancer Genes and Their Mutations 2

Identification of Cancer Genes 2

Cancer Genome Investigation: Tools and Quality Controls 2

Somatic Alteration Classes Detected by Cancer Genome Analysis 12

Pathway-Oriented Models of Cancer Genome Analysis 14

Networks of Cancer Genome Projects 16

The Genomic Landscape of Cancers 18

The Cancer Genome and the New Taxonomy of Tumors 18

Cancer Genomics and Drug Resistance 20

Perspectives of Cancer Genome Analysis 20

2.

Mechanisms of Genomic Instability . . . . . . . 23David J. Gordon, David A. Barbie, Alan D. D’Andrea,

and David Pellman

Basic Defenses Against Genomic Instability 23

Barriers to Genomic Instability 23

Mutations in Cancer 26

Mechanisms of Genome Destabilization in Human Tumors 29

What Causes Chromosomal Instability and Whole-Chromosome

Aneuploidy? 35

Does Whole-Chromosome Aneuploidy Cause Cancer? 37

Perspectives and Implications for Cancer Therapeutics 38

3.

Epigenetics of Cancer . . . . . . . . . . . . . . . . . . 41Peter A. Jones and Karin B. Michels

Epigenetic Processes 41

Epigenomic Changes in Cancer 43

The Timing of Epigenetic Alterations 44

Epigenetic Biomarkers for Early Detection of Cancer 44

Epigenetic Therapies 45

Problems with Epigenetic Therapies 46

4.

Telomeres, Telomerase, and Cancer . . . . . . . 48Kwok-Kin Wong, Norman E. Sharpless, and

Ronald A. DePinho

Telomeres and Telomerase 48

Senescence 50

Telomere Maintenance and Cancer 53

5.

Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Cell Signaling Growth Factors and TheirLewis C. Cantley, Chris L. Carpenter, William C. Hahn,

and Matthew Meyerson

Signal Transduction Systems 57

Sensory Machinery: Ligands and Receptors 57

Regulation of Protein Kinases 60

Small-Molecule Second Messengers 63

Efficiency and Specificity: Formation of Multiprotein Signaling

Complexes 64

Signaling Networks 66

6.

Cell Cycle. . . . . . . . . . . . . . . . . . . . . . . . . . . 68Steven I. Reed

Cell-Cycle Engine 68

Induction of Cell-Cycle Phase Transitions 71

Ubiquitin-Mediated Proteolysis 71

Regulation of the Cell Cycle 72

Cell Cycle and Cancer 76

MicroRNAs, the Cell Cycle, and Cancer 79

The Cell Cycle and Cancer Therapy 80

7.

Mechanisms of Cell Death . . . . . . . . . . . . . . 82Vassiliki Karantza and Eileen White

Apoptosis 82

Autophagy 87

Necrosis 89

8.

Cancer Metabolism . . . . . . . . . . . . . . . . . . . 91Matthew G. Vander Heiden

Altered Metabolism in Cancer Cells 91

Energetics of Cell Proliferation 93

Imaging Cancer Metabolism in Patients 94

Genetic Events Important for Cancer Influence Metabolism 95

Targeting Metabolism to Treat Cancer 99

9.

Angiogenesis . . . . . . . . . . . . . . . . . . . . . . . 101Robert S. Kerbel and Lee M. Ellis

Introduction: Origins of the Concept of Antiangiogenic Therapy for

Cancer 101

Sequential Steps Involved in the Formation of Blood Vessel Capillaries

in Tumors 101

Pericytes 102

Dysfunctional Nature of the Tumor Vasculature 102

Molecular Mediators of Tumor Angiogenesis: Angiogenic Stimulators

and Their Receptors 103

Endogenous Inhibitors of Tumor Angiogenesis 105

A Cooperative Regulator of Tumor Angiogenesis: The Notch Receptor-

DLL4 Signaling Pathway in Endothelial Cells 106

Strategies for Development of Antiangiogenic Drugs 106

Enhancement of Chemotherapy Efficacy and Other Therapeutic

Modalities by Antiangiogenic Drugs 107

Resistance to Antiangiogenic Drugs or Treatments 108

Biomarkers for Tumor Angiogenesis and Antiangiogenic Therapy 109

Antiangiogenic/Anti-VEGF Drug-Based Clinical Trials 109

Looking Ahead: New Targets, New Drugs, and New Strategies for

Antiangiogenic Therapy 111

10.

Invasion and Metastasis . . . . . . . . . . . . . . . 113Andy J. Minn and Joan Massagué

The Evolution and Pathogenesis of Metastasis 113

An Integrated Model for Metastasis 115

Selective Pressures at the Primary Tumor Driving Acquisition of

Metastasis Functions 117

Coupling Tumorigenesis with Metastasis Initiation 119

Coupling Tumorigenesis with Metastasis Progression 121

From Metastasis Progression to Macrometastatic Colonization 122

Micro-RNAs and Metastasis 126

11.

Cancer Stem Cells . . . . . . . . . . . . . . . . . . . 128Jean C. Y. Wang and John E. Dick

Tumor Heterogeneity 128

Leukemia Stem Cells 129

CONTENTS

xxxi

Cancer Stem Cells in Solid Tumors 130

Genetic Diversity and Clonal Evolution in Cancer 133

The Origins of Cancer Stem Cells 134

Epithelial-Mesenchymal Transition 137

Cancer Stem Cells: Targeted Therapy 137

12.

Biology of Personalized Cancer Medicine . . .141Raju Kucherlapati

Cancer Predisposition 141

Familial Adenomatous Polyposis 141

Lynch Syndrome 142

Other Polyposis Syndromes 142

Association Studies 142

Breast Cancer 142

Early Detection 143

Tumor Classification and Patient Stratification 143

Treatment 144

Development of Resistance to Tyrosine Kinase Inhibitors 145

Alternative Mechanisms of Resistance 145

BRAF Inhibitors 146

The Future 146

Changing Face of Personalized Medicine 146

Summary 146

PART TWO

ETIOLOGY AND EPIDEMIOLOGY

OF CANCER

Section 1: Etiology of Cancer

13. Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

Stephen S. Hecht

Epidemiology of Tobacco and Cancer 150

Tumor Induction in Laboratory Animals by Tobacco Products 152

Carcinogens in Tobacco Products 153

Overview of Mechanisms of Tumor Induction by Tobacco Products 156

Tobacco Carcinogen and Toxicant Biomarkers 157

14.

Cancer Susceptibility Syndromes . . . . . . . . 161Alice Hawley Berger and Pier Paolo Pandolfi

Principles of Cancer Susceptibility 161

Genetic Testing 163

Cancer Susceptibility Syndromes 164

Future Directions 170

15.

DNA Viruses . . . . . . . . . . . . . . . . . . . . . . . 173Peter M. Howley, Don Ganem, and Elliott Kieff

History of Viral Oncology 173

Hepadnaviruses and Hepatocellular Carcinoma 174

Papillomaviruses 176

Epstein-Barr Virus 180

Kaposi’s Sarcoma–Associated Herpesvirus 182

Human Polyomaviruses 184

16.

RNA Viruses . . . . . . . . . . . . . . . . . . . . . . . 186Gary L. Buchschacher, Jr. and Flossie Wong-Staal

Retroviruses: Background, Replication Cycle, and

Molecular Genetics 186

Human T-Lymphotropic Virus Type 1 189

Human T-Lymphotropic Virus Type 2 190

Human Immunodeficiency Virus 190

Hepatitis C Virus 190

17.

Inflammation . . . . . . . . . . . . . . . . . . . . . . . 193Giorgio Trinchieri

Tumor Immune Surveillance 193

Inflammation and Tumorigenesis 194

Mechanisms of Cell Transformation and Cancer Initiation in the

Inflammatory Environment 196

Inflammatory Cells and Stromal Cells in the Initiation of Neoplasia

and in the Tumor Microenvironment 198

18.

Chemical Factors . . . . . . . . . . . . . . . . . . . . 203Stuart H. Yuspa and Peter G. Shields

The Nature of Chemical Carcinogens: Chemistry

and Metabolism 203

Animal Model Systems and Chemical Carcinogenesis 205

DNA Repair Protects the Host from Chemical

Carcinogens 205

Genetic Susceptibility to Chemical Carcinogenesis 205

Molecular Epidemiology, Chemical Carcinogenesis, and

Cancer Risk in Human Populations 206

Polyclic Aromatic Hydrocarbons as a Model for Gene-Environment

Interaction 207

19.

Physical Factors . . . . . . . . . . . . . . . . . . . . . 209Mats Ljungman

Ionizing Radiation 209

Ultraviolet Light 212

Radiofrequency and Microwave Radiation 214

Electromagnetic Fields 214

Asbestos 214

Nanoparticles 215

20.

Dietary Factors . . . . . . . . . . . . . . . . . . . . . 217Karin B. Michels and Walter C. Willett

Methodologic Challenges 217

The Role of Individual Food and Nutrients in

Cancer Etiology 218

Other Foods and Nutrients 222

Dietary Patterns 224

Diet During Early Phases of Life 224

Summary 224

Limitations 224

Future Directions 225

Recommendations 225

21.

Obesity and Physical Activity . . . . . . . . . . . 227Katherine D. Henderson, Yani Lu, and Leslie Bernstein

Breast Cancer 227

Colon and Rectal Cancer 228

Endometrial Cancer 229

Adenocarcinoma of the Esophagus 229

Kidney/Renal Cell Cancer 230

Pancreatic Cancer 230

Gallbladder Cancer 230

Non-Hodgkin Lymphoma 230

Prostate Cancer 231

Lung Cancer 231

Ovarian Cancer 231

Overview 231

Section 2: Epidemiology of Cancer

22.

Epidemiologic Methods . . . . . . . . . . . . . . . 233Xiaomei Ma and Herbert Yu

Analytical Studies 233

Interpretation of Epidemiologic Findings 236

Molecular Epidemiology 237

23.

Global Cancer Incidence and Mortality . . . 241Michael J. Thun, Ahmedin Jemal, and Elizabeth Ward

Data Sources and Measurements 241

Overall Cancer Risk 243

Incidence and Mortality Patterns for Common Cancers 251

Issues in Interpreting Temporal Trends 258

Conclusion 259

xxxii

Contents24.

Trends in Cancer Mortality . . . . . . . . . . . . 261Tim E. Byers

Cancer Surveillance Systems 261

Making Sense of Cancer Trends 261

Trends in Cancer Risk Factors 261

Cancer Trends 263

Predicting Future Cancer Trends 265

PART THREE

PRINCIPLES OF CANCER TREATMENT

25.

Surgical Oncology: General Issues . . . . . . . 268Steven A. Rosenberg

Historical Perspective 268

Anesthesia for Oncologic Surgery 268

Determination of Operative Risk 270

Roles for Surgery 272

Surgical Oncologist 274

26.

Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

Surgical Oncology: LaparoscopicYoshinori Hosoya and Alan T. Lefor

New Technology 277

Physiology of Laparoscopy 278

Laparoscopy in the Diagnosis of Malignancy 279

Laparoscopy in the Staging of Malignancy 279

Laparoscopy in the Treatment of Malignancy 281

Laparoscopy in the Palliation of Malignancy 287

27.

Radiation Oncology . . . . . . . . . . . . . . . . . . 289Meredith A. Morgan, Randall K. Ten Haken, and

Theodore S. Lawrence

Biologic Aspects of Radiation Oncology 289

Factors that Affect Radiation Response 294

Drugs that Affect Radiation Sensitivity 296

Radiation Physics 297

Treatment Planning 301

Other Treatment Modalities 303

Clinical Applications of Radiation Therapy 304

Treatment Intent 305

Fractionation 306

Adverse Effects 307

Principles of Combining Anticancer Agents with Radiation Therapy 308

28.

Medical Oncology . . . . . . . . . . . . . . . . . . . 312Vincent T. DeVita, Jr. and Edward Chu

Introduction 312

Biology of Drug Resistance 316

29.

Assessment of Clinical Response . . . . . . . . 322Antonio Tito Fojo and Susan Elaine Bates

Overall Response Rate and Stable Disease 322

Alternate Response Criteria 323

Waterfall Plots 326

Progression Free Survival and Time to Progression 326

Overall Survival 327

Kaplan-Meier Plots 328

Hazard Ratios 329

Forest Plots 329

Meta-Analyses 329

Quality of Life 329

Novel End Points 329

30.

Cancer Immunotherapy . . . . . . . . . . . . . . . 332Steven A. Rosenberg, Paul F. Robbins, and Nicholas P. Restifo

Approaches to the Identification of Human

Tumor Antigens 332

Categories of Tumor Antigens Can Be Defined by Expression

Patterns 334

Cancer Immunotherapies 337

31.

of Cancer Care . . . . . . . . . . . . . . . . . . . . . . 345

Health Services Research and EconomicsCraig C. Earle and Deborah Schrag

Studies of Health Service Delivery in Cancer Medicine 345

Patient-Reported Outcomes Assessment 350

The Economics of Cancer Care 353

Comparative Effectiveness Research 356

PART FOUR

PHARMACOLOGY OF CANCER

THERAPEUTICS

Section 1: Chemotherapy Agents

32.

Pharmacokinetics and Pharmacodynamics . . . .360Chris H. Takimoto, Chee M. Ng, and Thomas Puchalski

Why Study Pharmacokinetics and Pharmacodynamics? 360

Cancer Patients Present Unique Challenges 361

Pharmacokinetic Concepts 361

Pharmacodynamic Concepts 365

Special Topics in Pharmacokinetics and Pharmacodynamics 365

Population Pharmacokinetics/Pharmacodynamics 366

Pharmacokinetics and Pharmacodynamics in Oncology Drug

Development 366

33.

Pharmacogenomics . . . . . . . . . . . . . . . . . . 369Anthony El-Khoueiry and Heinz Josef Lenz

Definitions: Terms and Concepts 369

Pharmacogenomics and Predictive Molecular Markers 369

Pharmacogenomics and Prognostic Markers 372

Current Challenges and Future Directions 373

34.

Alkylating Agents . . . . . . . . . . . . . . . . . . . . 375Kenneth D. Tew

Perspectives 375

Chemistry 375

Classification 375

Clinical Pharmacokinetics/Pharmacodynamics 380

Therapeutic Uses 381

Toxicities 381

Complications with High-Dose Alkylating Agent

Therapy 383

Alkylating Agent–Steroid Conjugates 383

Drug Resistance and Modulation 383

Recent Developments 383

35.

Platinum Analogs . . . . . . . . . . . . . . . . . . . . 386Eddie Reed

Common Features of Platinum Chemistry 387

Clinical Pharmacology 388

Determinants of Cellular Sensitivity and Resistance to

Platinum Agents 389

Cellular Accumulation and Cytosolic Inactivation

of Drug 390

DNA Damage and Repair 390

36.

Antimetabolites . . . . . . . . . . . . . . . . . . . . . 393M. Wasif Saif and Edward Chu

Antifolates 393

5-Fluoropyrimidines 396

Capecitabine 396

Cytarabine 397

Contents

xxxiiiGemcitabine 397

6-Thiopurines 398

Fludarabine 399

Cladribine 399

Clofarabine 400

37.

Topoisomerase-Interacting Agents . . . . . . . 402Zeshaan A. Rasheed and Eric H. Rubin

Topoisomerase Biology 402

Camptothecins 402

Anthracyclines 404

Anthracenediones 409

Epipodophyllotoxins 410

38.

Antimicrotubule Agents . . . . . . . . . . . . . . . 413Maysa M. Abu-Khalaf and Lyndsay N. Harris

Microtubules 413

Taxanes 413

New Taxane Formulations 416

Vinca Alkaloids 417

Estramustine Phosphate 420

Epothilones 420

Novel Compounds Targeting Microtubules and

Mitotic Motor Proteins 420

39.

Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . 422

Targeted Therapy with Small Molecule KinaseCharles L. Sawyers

Early Successes: Targeting Cancers with Well-Known Kinase

Mutations 422

Targeting the PI3K Pathway Directly 431

Combinations of Kinase Inhibitors 431

Speculations on the Future Role of Kinase Inhibitors in

Cancer Medicine 432

40.

Demethylating Agents . . . . . . . . . . . . . . . . 434

Histone Deacetylase Inhibitors andSteven D. Gore, Stephen B. Baylin, and James G. Herman

Epigenetics and Gene Silencing 434

Changes in DNA Methylation 434

Histone Deacetylase Inhibitors 437

Pharmacodynamic Observations 439

41.

Proteasome Inhibitors . . . . . . . . . . . . . . . . 441Michael G. Kauffman, Christopher J. Molineaux,

Christopher J. Kirk, and Craig M. Crews

Biochemistry of the Ubiquitin-Proteasome Pathway 441

Proteasome Inhibitors 441

Preclinical Pharmacology of PIs 445

Proteasome Inhibitors in Cancer 445

42.

Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . 450

Poly(ADP-Ribose) PolymeraseAlan Ashworth

Cellular DNA Repair Pathways 450

The Development of PARP Inhibitors 450

BRCA1

PARP1 Inhibition as a Synthetic Lethal Therapeutic Strategy for the

Treatment of BRCA-Deficient Cancers 451

Mechanisms of Resistance to PARP Inhibitors 452

Initial Clinical Results Testing Synthetic Lethality 452

The Use of PARP Inhibitors in Sporadic Cancers

with “BRCAness” 452

Prospects 453

and BRCA2 Mutations and DNA Repair 45143.

Miscellaneous Chemotherapeutic Agents . . . 455M. Sitki Copur, Michal Rose, and Scott Gettinger

Sirolimus and Temsirolimus 455

Everolimus 455

l-Asparaginase 456

Bleomycin 456

Procarbazine 457

Thalidomide 458

Lenalidomide 458

Section 2: Biotherapeutics

44.

Interferons . . . . . . . . . . . . . . . . . . . . . . . . . 461Vernon K. Sondak, Jürgen C. Becker, and Axel Hauschild

Interferon Signaling Pathways 461

Immunologic Effects of Interferon 463

Nonimmunologic Antiangiogenic Effects of Interferon 464

Direct Antitumor Effects of Interferons 464

Clinical Toxicity of Interferon Administration 464

Potential Drug Interactions 466

Oncologic Applications of Interferons 466

45.

Interleukin Therapy . . . . . . . . . . . . . . . . . . 469Michael T. Lotze

Interleukins as Therapeutics 469

Interleukin-1 Family 469

Interleukin 3, Interleukin 11, and Interleukin 34 470

Interleukin-2 Family 470

Interleukin 6 Family 477

Interleukin 10 Family 480

46.

Antisense Agents . . . . . . . . . . . . . . . . . . . . 482Cy A. Stein and Harris S. Soifer

Oligonucleotide Stability and Efficacy: The Role of

Phosphorothioates 482

Clinical Trials of G3139 (Oblimersen) in Chronic Lymphocytic

Leukemia 483

Clinical Trials in Advanced Melanoma 484

47.

Antiangiogenesis Agents . . . . . . . . . . . . . . . 489Cindy H. Chau and William D. Figg

Understanding the Angiogenic Process 489

Drug Development of Angiogenesis Inhibitors 490

Clinical Utility of Approved Antiangiogenic Agents in

Cancer Therapy 494

Combination Therapies 496

Surrogate Markers of Antiangiogenic Therapy 497

Resistance to Antiangiogenic Therapy 497

48.

Monoclonal Antibodies . . . . . . . . . . . . . . . 499Matthew K. Robinson, Hossein Borghaei, Gregory P. Adams,

and Louis M. Weiner

Immunoglobulin Structure 499

Modified Antibody-Based Molecules 499

Factors Regulating Antibody-Based Tumor Targeting 500

Unconjugated Antibodies 502

Altering Signal Transduction 503

Immunoconjugates 504

Unconjugated Antibodies Approved for Use Against Solid

Tumors 505

Antibodies Used in Hematologic Malignancies 506

49.

Endocrine Manipulation . . . . . . . . . . . . . . 508Matthew P. Goetz, Charles Erlichman, Manish Kohli, and

Charles L. Loprinzi

Selective Estrogen Receptor Modulators 508

Aromatase Inhibitors 513

Gonadotropin-Releasing Hormone Analogues 514

Gonadotropin-Releasing Hormone Antagonists 515

Antiandrogens 515

Novel Antiandrogens 516

Other Sex Steroid Therapies 516

Other Hormonal Therapies 518

xxxiv

ContentsPART FIVE

CANCER PREVENTION

50.

Preventive Cancer Vaccines. . . . . . . . . . . . . 522Douglas R. Lowy and John T. Schiller

Background 522

Infectious Agents and Cancer 522

Prophylactic Versus Therapeutic Vaccination 524

Hepatitis B Virus 524

Human Papillomavirus 525

Helicobacter Pylori

52751.

Tobacco Dependence and Its Treatment . . . 529Ellen R. Gritz, Cho Y. Lam, Damon J. Vidrine, and

Michelle Cororve Fingeret

Nicotine and the Neurobiological Basis of Smoking 529

Smoking Prevalence and Quit Rates 529

Effects of Continued Smoking on Cancer Treatment Outcomes 530

Cessation Treatment and Research 532

Future Research and Clinical Opportunities 540

52.

Role of Surgery in Cancer Prevention . . . . . 543José G. Guillem, Andrew Berchuck, Jeffrey F. Moley,

Jeffrey Norton, and Sheryl G. A. Gabram

Patients at High Risk for Breast Cancer 543

Hereditary Diffuse Gastric Cancer 545

Surgical Prophylaxis of Hereditary Ovarian and Endometrial

Cancer 547

Hereditary Endometrial Cancer (Lynch Syndrome) 548

Multiple Endocrine Neoplasia Type 2 549

Familial Adenomatous Polyposis,

and Lynch Syndrome 552

MYH-Associated Polyposis,53.

Intervention . . . . . . . . . . . . . . . . . . . . . . . . 558

Principles of Cancer Risk ReductionDean E. Brenner

Why Cancer Prevention as a Clinical Oncology Discipline? 558

Defining Cancer Risk Reductive Intervention

(Chemoprevention) 558

Identifying Potential Cancer Risk Reductive Interventions 558

Preclinical Development of Cancer Risk Reductive

Interventions 559

Clinical Development of Cancer Risk Reductive Interventions 561

Implementation of Cancer Risk Reductive Interventions in the

Community 562

54.

Micronutrients in Cancer Prevention . . . . . 564

Retinoids, Carotenoids, and OtherSusan T. Mayne, Edward Giovannucci, and Scott M. Lippman

Head and Neck Cancer Chemoprevention 564

Lung Cancer Chemoprevention 565

Breast Cancer Chemoprevention 567

Skin Cancer Chemoprevention 567

Bladder Cancer Chemoprevention 568

Cervical Cancer Chemoprevention 568

Esophageal/Gastric Cancer Chemoprevention 569

Colorectal Cancer Chemoprevention 569

Prostate Cancer Chemoprevention 570

Conclusions 571

55.

Reduction (Chemoprevention) . . . . . . . . . . 573

Drugs and Nutritional Extracts for Cancer RiskMadhuri Kakarala and Dean E. Brenner

Anti-Inflammatory Drugs 573

Signal Transduction Modifiers 578

Anti-Infectives 579

PART SIX

CANCER SCREENING

56.

Principles of Cancer Screening . . . . . . . . . . 582Jack S. Mandel and Robert Smith

Principles of Screening 582

Evaluating Screening Tests 583

Developing and Evaluating a Cancer Screening

Program 585

57.

Early Detection Using Proteomics . . . . . . . . 587Virginia Espina, Claudio Belluco, Emanuel F. Petricoin III, and

Lance A. Liotta

Cellular Proteomics 587

Biomarker Proteomics 592

58.

Screening for Gastrointestinal Cancers . . . . 596Timothy R. Church and Jack S. Mandel

History of Colorectal Cancer Screening 596

Polyp Removal and Colorectal Cancer Prevention 597

Methods of Screening for Colorectal Cancer 597

Colorectal Cancer Screening for High-Risk

Patients 600

Other Gastrointestinal Cancers 600

Screening 601

59.

Screening for Gynecologic Cancers . . . . . . 603Mary B. Daly and Janet S. Rader

Cervical Cancer 603

Ovarian Cancer 606

Endometrial Cancer 607

60.

Screening for Breast Cancer . . . . . . . . . . . . 610Laura J. Esserman and Chris I. Flowers

The Evidence of Mortality Benefit from Randomized Trials of

Mammography Screening 610

Changes in Systemic Therapies and Impact on Screening 610

Optimizing the Organization of Screening 611

Optimizing the Interpretation of Mammography 611

Addressing the Potential Harms and Limitations of

Screening 612

High-Risk Screening 614

What has Biology Taught Us? 614

Conclusion and Considerations for Screening 615

61.

Screening for Prostate Cancer . . . . . . . . . . 617Peter C. Albertsen

Is Prostate Cancer a Suitable Disease for

Screening? 617

Is Treatment for Prostate Cancer Effective? 618

Is Prostate-Specific Antigen an Effective Screening

Test? 620

Recent Evidence from Randomized Trials 621

Are there Substantial Risks Associated with Prostate-Specific Antigen

Screening? 622

How Should Physicians Advise their Patients? 622

62.

Screening for Lung Cancer . . . . . . . . . . . . . 625David E. Midthun and James R. Jett

The Opportunity 625

Chest Radiography and Sputum Cytology 625

CT Screening 626

The Problems with CT Screening 627

Other Methods of Screening 629

Future Directions 629

Contents

xxxv63.

Genetic Counseling . . . . . . . . . . . . . . . . . . 631Ellen T. Matloff and Danielle Campfield Bonadies

Who is a Candidate for Cancer Genetic Counseling? 631

Components of the Cancer Genetic Counseling Session 632

Issues in Cancer Genetic Counseling 635

Future Directions 637

PART SEVEN

SPECIALIZED TECHNIQUES IN

CANCER MANAGEMENT

64.

Techniques . . . . . . . . . . . . . . . . . . . . . . . . . 640

Vascular Access and SpecializedJames F. Pingpank, Jr.

Catheter Types 640

Catheter Selection 643

Pediatric Patients 643

Insertion Techniques 643

Catheter-Related Complications 645

65.

Interventional Radiology . . . . . . . . . . . . . . 648Christos S. Georgiades and Jean-Francois H. Geschwind

Pulmonary 648

Hepaticobiliary 649

Cholangiocarcinoma 652

Liver Metastases 655

Genitourinary 657

Musculoskeletal Cancer 659

Special Topic: Inferior Vena Cava/Portal Vein

Occlusion 661

66.

Functional Imaging . . . . . . . . . . . . . . . . . . 666Brian D. Ross, Craig J. Galbán, and

Alnawaz Rehemtulla

Diffusion Magnetic Resonance Imaging 666

Perfusion Magnetic Resonance Imaging 670

Magnetic Resonance Spectroscopy 672

67.

Molecular Imaging . . . . . . . . . . . . . . . . . . . 676Steven M. Larson, Heiko Schöder, and Jan Grimm

Characterizing the Cancer Cell Phenotype 676

Clinical Applications 680

Optical Imaging 683

68.

Photodynamic Therapy . . . . . . . . . . . . . . . 686Keith A. Cengel, Smith Apisarnthanarax, and

Stephen M. Hahn

Components of Photodynamic Therapy: Photosensitizers,

Light, and Oxygen 686

Mechanisms of Photodynamic Therapy Cytotoxicity 688

Clinical Indications for Photodynamic Therapy for Early Stage Cancers

in the Definitive Setting 689

Clinical Indications for Photodynamic Therapy in the Locally

Advanced and Palliative Settings 690

Molecularly Targeted Photodynamic Therapy 692

69.

Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . 694Daniel F. Hayes

What is a Biomarker Used for? 694

What are the Criteria to Incorporate a Tumor Marker into

Clinical Practice? 695

Prognosis Versus Prediction 698

Pharmacogenomics: A Special Circumstance 698

Markers that are Accepted for Routine Clinical Utility 700

PART EIGHT

PRACTICE OF ONCOLOGY

70.

Design and Analysis of Clinical Trials . . . . 704Richard Simon

Phase 1 Clinical Trials 704

Phase 2 Clinical Trials 706

Design of Phase 3 Clinical Trials 711

Factorial Designs 713

Analysis of Phase 3 Clinical Trials 716

Reporting Results of Clinical Trials 719

False-Positive Reports in the Literature 720

Meta-Analysis 720

Section 1: Cancer of the Head and Neck

71.

Neck Cancers . . . . . . . . . . . . . . . . . . . . . . . 723

Molecular Biology of Head andNishant Agrawal, Joseph Califano, and

Patrick Ha

Genetic Susceptibility 723

Molecular Networks Altered in HNSCC 724

Epigenetics 727

Loss of Heterozygosity and Risk of Malignant Progression 727

72.

Treatment of Head and Neck Cancer . . . . . 729William M. Mendenhall, John W. Werning, and

David G. Pfister

Epidemiology of Head and Neck Cancer 729

Anatomy 729

Pathology 729

Natural History of Squamous Cell Carcinoma 729

Diagnostic Evaluation 730

Staging 731

Principles of Treatment for Squamous Cell Carcinoma 731

Management 731

NECK 732

Chemotherapy 734

General Principles of Combining Modalities 738

Chemotherapy as Part of Curative Treatment 738

Follow-Up 744

ORAL CAVITY 744

Lip 744

Floor of the Mouth 745

Oral Tongue 747

Buccal Mucosa 749

Gingiva and Hard Palate (Including Retromolar

Trigone) 750

OROPHARYNX 752

Anatomy 752

LARYNX 756

Anatomy 756

Pathology 756

Hypopharynx: Pharyngeal Walls, Pyriform Sinus, and

Postcricoid Pharynx 761

NASOPHARYNX 764

Anatomy 764

Pathology 764

Patterns of Spread 765

Clinical Picture 765

Staging 765

Treatment 766

Nasal Vestibule, Nasal Cavity, and Paranasal Sinuses 766

Paragangliomas 772

Major Salivary Glands 774

Minor Salivary Glands 777

xxxvi

Contents73.

Neck Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . .781

Rehabilitation after Treatment of Head andDouglas B. Chepeha, Mark J. Haxer, and Teresa H. Lyden

Pretreatment Counseling 781

Support During Treatment and Rehabilitation of the

Chemoradiation Patient 781

Resources for Rehabilitation of Head and Neck Cancer Patients 787

Section 2: Cancer of the Thoracic Cavity

74.

Molecular Biology of Lung Cancer . . . . . . 789Jacob Kaufman, Leora Horn, and David Carbone

Susceptibility to Lung Cancer: Genetic Susceptibility and Carcinogens

in Tobacco Smoke 789

Molecular Changes in Preneoplasia 789

Genetic and Epigenetic Alterations in Lung Cancers 791

Protooncogenes, Growth Factor Signaling, and Growth Factor Targeted

Therapies 791

Tumor Suppressor Genes and Growth Suppression 793

Cyclins and Cell Cycle Regulatory Pathways 794

Other Biologic Abnormalities in Lung Cancer 795

Cancer Stem Cell Hypothesis 796

Genomic Analysis of Lung Cancer 797

Molecular Tools in the Lung Cancer Clinic 797

75.

Non–Small Cell Lung Cancer . . . . . . . . . . . 799David S. Schrump, Darryl Carter, Christopher R. Kelsey,

Lawrence B. Marks, and Giuseppe Giaccone

Incidence 799

Etiology 799

Pathology 802

Molecular Markers of Prognosis 805

Modes of Metastasis 806

Clinical Manifestations 806

Staging and Diagnosis 807

Methods to Establish Tissue Diagnosis 811

Overview of Invasive Lung Cancer Management:

Treatment Modalities 813

Specifics of Lung Cancer Management 820

Superior Sulcus Tumors 829

Unresectable or Medically Inoperable 829

Locally Advanced 830

Advanced Disease 833

Investigational Agents in Development for NSCLC 843

Personalized Medicine in NSCLC 843

Local Therapies and Palliation 844

76.

the Lung. . . . . . . . . . . . . . . . . . . . . . . . . . . 848

Small Cell and Neuroendocrine Tumors ofLee M. Krug, M. Catherine Pietanza, Mark G. Kris,

Kenneth Rosenzweig, and William D. Travis

Small Cell Lung Cancer 848

Typical Carcinoid and Atypical Carcinoid Tumors 863

Large Cell Neuroendocrine Carcinoma 867

77.

Neoplasms of the Mediastinum . . . . . . . . . 871Robert B. Cameron, Patrick J. Loehrer, and

Charles R. Thomas, Jr.

Thymic Neoplasms 871

Thymoma 871

Thymic Carcinoma 872

Thymic Carcinoid 878

Thymolipoma 878

Germ Cell Tumors 878

Section 3: Cancers of the Gastrointestinal Tract

78.

Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . 882

Molecular Biology of the Esophagus andAnil K. Rustgi

Molecular Biology of Esophageal Cancer 882

Molecular Biology of Gastric Cancer 884

79.

Cancer of the Esophagus . . . . . . . . . . . . . . 887Mitchell C. Posner, Bruce D. Minsky, and David H. Ilson

Epidemiology 887

Etiologic Factors and Predisposing Conditions 887

Applied Anatomy and Histology 891

Natural History and Patterns of Failure 892

Clinical Presentation 892

Diagnostic Studies and Pretreatment Staging 893

Pathologic Staging 894

Treatment 895

Stage-Directed Treatment Recommendations 921

80.

Cancer of the Stomach . . . . . . . . . . . . . . . . 924Itzhak Avital, Peter W.T. Pisters, David P. Kelsen, and

Christopher G. Willett

Epidemiology and Etiology 924

Anatomic Considerations 926

Pathology and Tumor Biology 927

Histopathology 927

Patterns of Spread 927

Clinical Presentation and Pretreatment Evaluation 928

Pretreatment Staging 929

Staging, Classification, and Prognosis 930

Gastric Cancer Nomograms: Predicting Individual Patient Prognosis

After Potentially Curative Resection 933

Treatment of Localized Disease 934

Technical Treatment-Related Issues 944

Treatment of Advanced Disease (Stage IV) 945

Surgery in Treatment of Metastatic Gastric Cancer 952

Radiation for Palliation 952

81.

Molecular Biology of Pancreas Cancer . . . . 955Scott E. Kern and Ralph H. Hruban

Common Molecular Changes 955

Low-Frequency Genetic Changes 958

82.

Cancer of the Pancreas . . . . . . . . . . . . . . . . 961Richard E. Royal, Robert A. Wolff, and Christopher H. Crane

Incidence and Etiology 961

Anatomy and Pathology 964

Screening 964

Diagnosis and Staging 965

Staging 967

Treatment of Potentially Resectable Disease: American Joint

Committee on Cancer Stage I and II 967

Treatment of Locally Advanced Disease: American Joint Committee on

Cancer Stage III 975

Treatment of Metastatic Disease: American Joint Committee on Cancer

Stage IV 980

Other Exocrine Neoplasms 986

83.

Molecular Biology of Liver Cancer . . . . . . 990Snorri S. Thorgeirsson and Joe W. Grisham

Allelic Imbalance in Liver Cancer 990

Classification and Prognostic Prediction of Hepatocellular

Carcinoma 991

Comparative Functional Genomics 995

Conclusion and Perspective 995

Contents

xxxvii84.

Cancer of the Liver . . . . . . . . . . . . . . . . . . 997David L. Bartlett, Adrian M. Di Bisceglie, and

Laura A. Dawson

Epidemiology 997

Etiologic Factors 997

Pathology 1001

Staging 1002

Clinical Features 1002

Clinical Evaluation 1004

Clinical Management 1008

Adjuvant Therapy 1012

Treatment of Other Primary Liver Tumors 1016

85.

Cancer of the Biliary Tree . . . . . . . . . . . . 1019David L. Bartlett, Ramesh K. Ramanathan, and

Edgar Ben-Josef

Cholangiocarcinomas 1019

Tumors of the Gallbladder 1035

86.

Cancer of the Small Intestine . . . . . . . . . . 1048Amer H. Zureikat, Matthew T. Heller, and Herbert J Zeh, III

Small Bowel Cancer 1048

Adenocarcinoma 1052

Carcinoid Tumors 1053

Intestinal Lymphoma 1055

Gastrointestinal Stromal Tumors 1056

Other Mesenchymal Tumors 1057

87.

Gastrointestinal Stromal Tumor . . . . . . . . 1060George D. Demetri

GIST as a Unique Clinicopathologic Subset of Sarcoma 1060

GIST Cells are Related to the Mesenchymal Precursor Cells

that Give Rise to Normal Interstitial Cells of Cajal:

Aberrant Developmental Biology 1061

The Development of a Molecular Understanding of GIST 1061

Clinical Considerations 1062

Prognostic Features of Gastrointestinal Stromal Tumor 1064

Diagnostic Imaging of Patients with Gastrointestinal

Stromal Tumors 1064

Treatment Options and Management Decisions in the Era of

Molecularly Targeted Therapies for GIST 1065

Extrapolation of Emerging Management Paradigms to

Early-Stage GIST 1070

Adjuvant Therapy to Improve Outcomes for Patients with

Resected Early-Stage GIST 1070

Special Considerations in GIST 1071

New Challenges and Alternative Approaches 1071

88.

Molecular Biology of Colorectal Cancer . 1074Ramesh A. Shivdasani

The Adenoma–Carcinoma Sequence and Multistep Models of

Colorectal Tumorigenesis 1074

Early Events and Critical Pathways in Colorectal Tumorigenesis

Highlighted by Inherited Syndromes of Increased Cancer

Risk 1075

Oncogene and Tumor Suppressor Gene Mutations in Colorectal Cancer

Progression 1079

Infrequent Changes and Current Views of the Mutational

Landscape of Colorectal Cancer 1082

89.

Cancer of the Colon . . . . . . . . . . . . . . . . . 1084Steven K. Libutti, Leonard B. Saltz, and Christopher G. Willett

Epidemiology 1084

Etiology: Genetic and Environmental Risk Factors 1085

Familial Colorectal Cancer 1086

Anatomy of the Colon 1088

Diagnosis of Colorectal Cancer 1089

Screening for Colorectal Cancer 1089

Staging and Prognosis of Colorectal Cancer 1090

Approaches to Surgical Resection of Colon Cancer 1096

Surgical Management of Complications from Primary

Colon Cancer 1098

Polyps and Stage I Colon Cancer 1099

Stage II and Stage III Colon Cancer 1099

Treatment of Stage II Patients 1102

Treatment Options for Stage III Patients 1104

Radiation Therapy of Colon Cancer 1104

Follow-Up After Management of Colon Cancer with

Curative Intent 1106

Surgical Management of Stage IV Disease 1108

Management of Unresectable Metastatic Disease 1108

Gene Therapy 1123

Molecular Predictive Markers 1123

Management of Synchronous Primary and

Metastatic Disease 1123

Unusual Colorectal Tumors 1124

90.

Cancer of the Rectum . . . . . . . . . . . . . . . 1127Steven K. Libutti, Christopher G. Willett, and Leonard B. Saltz

Anatomy 1127

Staging 1128

Surgery 1130

Does Adjuvant Radiation Therapy Impact

Survival? 1134

Preoperative Radiation Therapy 1135

Which Patients Should Receive Adjuvant Therapy? 1136

Concurrent Chemotherapy 1137

Synchronous Rectal Primary and Metastases 1138

Management of Unresectable Primary and Locally

Advanced Disease (T4) 1138

Radiation Therapy Technique 1139

91.

Cancer of the Anal Region . . . . . . . . . . . . 1142Yixing Jiang, David J. Beddy, Heidi Nelson, Lisa A. Kachnic,

and Jaffer A. Ajani

Epidemiology and Etiology 1142

Pathology 1143

Clinical Presentation and Staging 1144

Prognostic Factors 1144

Treatment of Localized Squamous Cell Carcinoma of the

Anal Canal 1145

Treatment of Other Sites and Pathologies 1151

Section 4: Cancers of the Genitourinary System

92.

Molecular Biology of Kidney Cancer . . . . 1154W. Marston Linehan and Laura S. Schmidt

Von Hippel-Lindau 1154

Hereditary Papillary Renal Carcinoma Type 1 1155

XP11.2 Translocation Renal Cell Cancer 1156

Birt-Hogg-Dubé Syndrome 1156

Hereditary Leiomyomatosis and Renal Cell Carcinoma 1157

Familial Renal Cancer: Succinate Dehydrogenase Gene 1158

Tuberous Sclerosis Complex 1159

Conclusion 1159

93.

Cancer of the Kidney . . . . . . . . . . . . . . . . 1161W. Marston Linehan, Brian I. Rini, and James C. Yang

Histologic Types of Renal Carcinoma 1161

Hereditary Forms of Kidney Cancer 1161

Transcription Factors and Kidney Cancer 1164

Localized Renal Carcinoma 1169

Metastatic Renal Carcinoma 1170

94.

Molecular Biology of Bladder Cancer . . . 1183Margaret A. Knowles

Molecular Alterations in Superficial Urothelial Carcinoma 1183

Carcinoma in Situ 1186

Molecular Alterations in Invasive Urothelial Carcinoma 1186

xxxviii

ContentsInformation from Expression and Genomic Microarray

Profiling 1188

Signaling Pathways in Urothelial Carcinoma 1189

Urothelial Tumor-Initiating Cells 1189

Molecular Pathogenesis and Tumor Clonality 1189

95.

Renal Pelvis . . . . . . . . . . . . . . . . . . . . . . . 1192

Cancer of the Bladder, Ureter, andW. Scott McDougal, William U. Shipley, Donald S. Kaufman,

Douglas M. Dahl, M. Dror Michaelson, and

Anthony L. Zietman

Urothelial Cancers 1192

Cancer of the Bladder 1194

Cancers of the Renal Pelvis and Ureter 1205

96.

Molecular Biology of Prostate Cancer . . . 1212Yu Chen, Vivek K. Arora, and Charles L. Sawyers

Genetic Predisposition 1212

Genetic Landscape of Prostate Cancer 1212

ETS Transcription Factors 1216

97.

Cancer of the Prostate . . . . . . . . . . . . . . . 1220Michael J. Zelefsky, James A. Eastham, and A. Oliver Sartor

Anatomy of the Prostate 1220

Prostate Zonal Anatomy 1220

Histopathology 1220

Gleason Score 1222

Incidence, Epidemiology, and Risk Factors 1222

Incidence and Mortality of Prostate Cancer 1223

Clinical Risk Factors for Prostate Cancer 1223

Genetic Alterations and Risk 1224

Prostate Cancer Prevention 1224

Disease Presentation and Diagnosis 1227

Staging Workup 1228

Prognostic Factors and the Assessment of Risk 1230

Treating Clinically Localized Prostate Cancer 1231

External-Beam Radiotherapy 1238

Androgen Deprivation and Radiation Therapy 1249

Adjuvant Radiation Therapy for High-Risk Patients After Radical

Prostatectomy 1252

Management of the Rising PSA After Definitive Local Therapy 1253

Management of Metastatic Prostate Cancer 1258

Castration-Resistant Prostate Cancer 1262

98.

Cancer of the Urethra and Penis . . . . . . . . 1272Edouard J. Trabulsi and Leonard G. Gomella

Cancer of the Male Urethra 1272

Carcinoma of the Female Urethra 1273

Cancer of the Penis 1274

99.

Cancer of the Testis . . . . . . . . . . . . . . . . . 1280George J. Bosl, Darren R. Feldman, Dean F. Bajorin,

Joel Sheinfeld, Robert J. Motzer, Victor E. Reuter,

Marisa A. Kollmeier, and Raju S. K. Chaganti

Background: Incidence 1280

Epidemiology 1280

Risk Factors 1280

Initial Presentation and Management 1280

Histology 1281

Biology 1282

Immunohistochemical Markers 1284

Staging 1284

Management of Clinical Stage I Disease 1286

Management of Clinical Stage II (Low Tumor Burden) 1290

Management of Stage II and Stage III Disease

(High Tumor Burden) 1291

Management of Relapse and Refractory Disease 1296

Treatment Sequelae 1298

Long-Term Follow-Up 1299

Midline Tumors of Uncertain Histogenesis 1299

Other Testicular Tumors 1299

Section 5: Gynecologic Cancers

100.

Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . 1302

Molecular Biology of GynecologicKunle Odunsi, Tanja Pejovic, and Matthew L. Anderson

Ovarian Cancer 1302

Endometrial Cancer 1306

Cervix, Vaginal, and Vulvar Cancers 1307

Gestational Trophoblastic Disease 1309

101.

Vulva . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Cancer of the Cervix, Vagina, andPatricia J. Eifel, Jonathan S. Berek, and Maurie A. Markman

Carcinoma of the Cervix 1311

Carcinoma of the Vagina 1330

Carcinoma of the Vulva 1335

102.

Cancers of the Uterine Body . . . . . . . . . . 1345Pedro T. Ramirez, Arno J. Mundt, and Franco M. Muggia

Endometrial Carcinoma 1345

Uterine Sarcomas 1356

103.

Gestational Trophoblastic Neoplasms . . . 1363Donald P. Goldstein and Ross S. Berkowitz

Epidemiology 1363

Pathology and Natural History 1363

Indications for Treatment 1363

Measurement of hCG 1364

Phantom hCG 1364

Pretreatment Evaluation 1364

Staging and Prognostic Score 1364

Treatment 1364

Placental Site Trophoblastic Tumors 1366

Subsequent Pregnancy 1366

Psychosocial Issues 1366

104.

Peritoneal Carcinoma . . . . . . . . . . . . . . . . . . .1368

Ovarian Cancer, Fallopian Tube Carcinoma, andStephen A. Cannistra, David M. Gershenson, and Abram Recht

Epithelial Ovarian Cancer 1368

Borderline Tumors 1385

Germ Cell Tumors of the Ovary 1386

Sex Cord–Stromal Tumors 1387

Primary Peritoneal Serous Carcinoma 1389

Fallopian Tube Cancer 1389

Section 6: Cancer of the Breast

105.

Molecular Biology of Breast Cancer . . . . 1392Erin Wysong Hofstatter, Gina G. Chung, and Lyndsay N. Harris

Genetics of Breast Cancer 1392

Hereditary Breast Cancer 1392

Somatic Changes in Breast Cancer 1393

Gene Expression Patterns in Breast Cancer 1395

Epigenetics of Breast Cancer 1396

Protein/Pathway Alterations 1397

106.

Malignant Tumors of the Breast . . . . . . . 1401Harold J. Burstein, Jay R. Harris, and Monica Morrow

Anatomy of the Breast 1401

Risk Factors for Breast Cancer 1401

Benign Breast Disease 1404

Breast Density 1404

Environmental Factors 1404

Management of the High-Risk Patient 1404

Contents

xxxixDiagnosis and Biopsy 1407

Lobular Carcinoma

Ductal Carcinoma

Treatment of the Breast 1409

Treatment of the Axilla 1411

Endocrine Therapy 1411

Staging 1411

Pathology of Breast Cancer 1413

Local Management of Invasive Cancer 1414

Breast-Conserving Therapy 1414

Mastectomy 1422

Management of the Axilla 1423

Local-Regional Therapy and Survival 1425

Prognostic and Predictive Factors 1426

Other Factors 1427

Molecular and Genomic Factors 1427

Adjuvant Systemic Therapy 1428

Integration of Multimodality Primary Therapy 1434

Follow-Up for Breast Cancer Survivors 1435

Special Therapeutic Problems 1436

Metastatic Disease 1439

In Situ 1408In Situ 1409Section 7: Cancer of the Endocrine System

107.

Molecular Biology of Endocrine Tumors . 1447Samuel A. Wells, Jr.

The Multiple Endocrine Neoplasia Syndromes 1447

Application of Molecular Genetics to Clinical Medicine 1452

Sporadic Thyroid Cancers 1453

Future Directions 1455

108.

Thyroid Tumors . . . . . . . . . . . . . . . . . . . . . . .1457Tobias Carling and Robert Udelsman

Thyroid Tumor Classification and Staging Systems 1457

Epidemiology and Demographics 1458

Etiology and Risk Factors 1458

Evaluation of the Thyroid Nodule 1460

Well-Differentiated Thyroid Carcinoma 1462

Treatment of Well and Intermediately Differentiated Thyroid

Carcinoma 1464

Poorly Differentiated Thyroid Carcinoma 1468

Medullary Thyroid Carcinoma 1469

Treatment of Familial Medullary Thyroid Carcinoma 1470

Thyroid Lymphoma 1470

Metastatic Disease of the Thyroid 1471

Children with Thyroid Carcinoma 1471

109.

Parathyroid Tumors . . . . . . . . . . . . . . . . . 1473Reza Rahbari and Electron Kebebew

Epidemiology 1473

Pathology 1474

Molecular Genetics 1475

Clinical Manifestations 1475

Diagnosis 1475

Management of Parathyroid Cancer 1476

Follow-Up and Natural History 1477

Prognosis 1478

110.

Adrenal Tumors . . . . . . . . . . . . . . . . . . . . 1480Mio Kitano, Erin Patterson, and Electron Kebebew

Adrenocortical Cancer 1480

Pediatric Adrenocortical Carcinoma 1484

Pheochromocytoma 1484

Adrenal Incidentaloma 1487

111.

Pancreatic Neuroendocrine Tumors . . . . . 1489James C. Yao, Guido Rindi, and Douglas B. Evans

Epidemiology 1489

Classification, Histopathology, and Molecular Genetics 1489

Diagnosis and Management of Pancreatic Endocrine Tumors 1492

Additional Clinical Considerations 1499

Surgery Pitfalls 1500

Emerging Therapeutic Options 1501

112.

Carcinoid Syndrome . . . . . . . . . . . . . . . . 1503

Neuroendocrine (Carcinoid) Tumors and theGerard M. Doherty

Pathology and Tumor Histology 1503

Molecular Pathogenesis 1506

Clinical Features of Carcinoid Tumors 1506

Carcinoid Syndrome 1506

Treatment of the Carcinoid Tumor 1512

113.

Multiple Endocrine Neoplasias . . . . . . . . 1516Gerard M. Doherty

Multiple Endocrine Neoplasia Type 1 1516

Familial Medullary Thyroid Carcinoma and Multiple Endocrine

Neoplasia Types 2A and 2B 1519

Section 8: Sarcomas of Soft Tissue and Bone

114.

Molecular Biology of Soft Tissue Sarcoma 1522Samuel Singer, Torsten Nielsen, and Cristina R. Antonescu

Translocation-Associated Sarcomas 1522

Simple Karyotype Tumors Associated with Mutations 1528

Complex Sarcoma Types 1528

Future Directions: Functional Screens and Next-Generation

Sequencing 1531

115.

Soft Tissue Sarcoma . . . . . . . . . . . . . . . . . 1533Samuel Singer, Robert G. Maki, and Brian O’Sullivan

Incidence and Etiology 1533

Anatomic and Age Distribution and Pathology 1535

Diagnosis and Staging 1547

Management by Presentation Status, Extent of Disease, and Anatomic

Location 1552

Palliative Care 1574

Future Directions 1576

116.

Sarcomas of Bone . . . . . . . . . . . . . . . . . . 1578Martin M. Malawer, Lee J. Helman, and Brian O’Sullivan

Classification and Types of Bone Tumor 1578

Radiographic Evaluation and Diagnosis 1578

Natural History 1579

Staging Bone Tumors 1581

Preoperative Radiographic Evaluation 1581

Biopsy Technique and Timing 1585

Restaging After Induction (Preoperative) Chemotherapy 1585

Guidelines for Limb-Sparing Resection 1586

Types of Skeletal Reconstruction 1586

Limb-Sparing Surgery and Perioperative Pain Management 1587

Amputations 1588

Chemotherapy for Bone Sarcomas 1589

Radiotherapy for Osteosarcoma 1594

Malignant Bone Tumors 1595

Section 9: Cancers of the Skin

117.

Cancer of the Skin . . . . . . . . . . . . . . . . . . 1610Anetta Reszko, Sumaira Z. Aasi, Lynn D. Wilson, and

David J. Leffell

NONMELANOMA SKIN CANCER 1610

Diagnosis 1610

General Approach to Management of Skin Cancer 1610

Topical Therapy for Skin Cancer 1613

Radiation Therapy for Skin Cancer 1614

ACTINIC KERATOSES 1614

xl

ContentsPathogenesis of AK 1615

Clinical Features of AK 1615

Treatment of AK 1615

BASAL CELL CARCINOMA 1616

Clinical Behavior of BCC 1617

BCC Subtypes 1617

Histology 1618

Treatment 1619

SQUAMOUS CELL CARCINOMA 1620

Pathogenesis of SCC 1620

Biologic Behavior of SCC 1620

Clinical Features of SCC 1621

Histology 1621

Recurrence and Metastatic Risk 1621

Treatment 1622

Follow Up 1623

Immunosuppression and Nonmelanoma Skin Cancer 1623

ANGIOSARCOMA 1624

Pathogenesis 1624

Clinical Presentation and Prognosis 1624

Histology 1625

Treatment 1625

DERMATOFIBROSARCOMA PROTUBERANS 1625

Pathogenesis 1625

Histology 1625

Treatment 1625

Recurrence and Metastatic Potential 1626

MERKEL CELL CARCINOMA 1626

Pathogenesis 1626

Clinical Presentation 1626

Histology 1626

Treatment 1627

Staging 1627

Recurrence and Metastatic Risk 1627

Prognosis 1628

MICROCYSTIC ADNEXAL CARCINOMA 1628

Pathogenesis 1629

Clinical Presentation 1629

Histology 1629

Treatment 1629

SEBACEOUS CARCINOMA 1629

Histology 1630

Treatment 1630

ATYPICAL FIBROXANTHOMA AND MALIGNANT

FIBROUS HISTIOCYTOMA 1630

ATYPICAL FIBROXANTHOMA 1630

Pathogenesis 1630

Clinical Presentation 1630

Histology 1631

Treatment 1631

MALIGNANT FIBROUS HISTIOCYTOMA 1631

Clinical Presentation 1631

Histology 1631

Treatment and Prognosis 1631

CARCINOMA METASTATIC TO SKIN 1631

118.

Melanoma . . . . . . . . . . . . . . . . . . . . . . . . 1634

Molecular Biology of CutaneousLevi A. Garraway and Lynda Chin

The

The Retinoblastoma Pathway 1634

The p53 Pathway 1635

The MAP Kinase Pathway 1636

The RAS Family: H-, N-, and K-RAS 1636

The Phosphatidylinositol 3-Kinase Pathway 1638

Receptor Tyrosine Kinases 1638

Epidermal Growth Factor Receptor Family 1639

The MITF Pathway 1639

The WNT Pathway 1639

The MC1R Pathway 1640

The FAK Pathway 1640

Cancer Stem Cells and Melanoma 1640

Cancer Genomics and Translation 1640

Looking Ahead 1641

CDKN2A Locus 1634119.

Cutaneous Melanoma . . . . . . . . . . . . . . . 1643Craig L. Slingluff Jr., Keith Flaherty, Steven A. Rosenberg, and

Paul W. Read

Cutaneous Melanoma Biology 1643

Epidemiology 1644

Changes in Incidence 1645

Gender and Age Distribution 1645

Melanoma in Children, Infants, and Neonates 1645

Anatomic Distribution 1646

Etiology and Risk Factors 1646

Pregnancy and Estrogen Use 1646

Prevention and Screening 1647

Diagnosis of Primary Melanoma 1648

General Considerations in Clinical Management of a Newly Diagnosed

Cutaneous Melanoma (Stage I–II) 1652

Wide Local Excision for Clinical Stage I–II Melanoma: General

Considerations 1653

Clinical Trials to Define Margins of Excision for Primary

Cutaneous Melanomas 1653

Surgical Staging of Regional Nodes 1655

Management of Clinically Localized Melanoma 1658

Management of Thin Primary Melanoma (Clinical T1a) 1658

Management of Clinical T2a, T2b Melanomas 1660

Management of Clinical T3a Melanomas (Clinical Stage IIA) 1660

Management of Clinical T3b Melanomas (Clinical Stage IIB) 1660

Management of Thick Melanomas (T4a, T4b, Greater than

4 mm Thick) 1660

Special Considerations in Management of Primary Melanomas 1661

The Role of Radiation Therapy in the Management of Primary

Melanoma Lesions 1662

Clinical Follow-Up for Intermediate-Thickness and Thick Melanomas

(Stage IB–IIC) 1662

Regionally Metastatic Melanoma (Stage III): Lymph Node Metastasis,

Satellite Lesions, and In-Transit Metastases 1662

Management of Regional Metastases in Patients with

Visceral or Other Distant Disease 1666

Adjuvant Systemic Therapy (Stages IIB, IIC, and III) 1667

Management of Distant Metastases of Melanoma (Stage IV) 1672

Combination Chemotherapy 1678

Experimental and Developing Immunologic Therapies for

Stage IV Melanoma 1682

Rationale for Targeted Therapy in Melanoma 1684

Radiation Therapy for Metastatic Melanoma (Stage IV) 1687

Section 10: Neoplasms of the

Central Nervous System

120.

System Tumors . . . . . . . . . . . . . . . . . . . . . 1692

Molecular Biology of Central NervousC. David James, David N. Louis, and Webster K. Cavenee

Neurologic Tumor Syndromes 1692

CNS Tumor Histopathology and Molecular Correlates 1692

Current Basis of CNS Tumor Treatment and

Response to Therapy 1698

121.

Neoplasms of the Central Nervous System 1700Minesh Mehta, Michael A. Vogelbaum, Susan Chang, and

Neha Patel

Epidemiology of Brain Tumors 1700

Anatomic Location and Clinical Considerations 1702

Neurodiagnostic Tests 1705

Surgery 1706

Radiation Therapy 1708

Chemotherapy and Targeted Agents 1710

Specific Central Nervous System Neoplasms 1712

Gliomatosis Cerebri 1720

Optic, Chiasmal, and Hypothalamic Gliomas 1720

Brainstem Gliomas 1722

Cerebellar Astrocytomas 1723

Gangliogliomas 1723

Ependymoma 1724

Contents

xlixlii

ContentsMeningiomas 1727

Primitive Neuroectodermal or Embryonal Central Nervous

System Neoplasms 1730

Pineal Region Tumors and Germ Cell Tumors 1733

Pituitary Adenomas 1735

Craniopharyngiomas 1737

Vestibular Schwannomas 1738

Glomus Jugulare Tumors 1740

Hemangioblastomas 1741

Chordomas and Chondrosarcomas 1742

Choroid Plexus Tumors 1744

Spinal Axis Tumors 1745

Section 11: Cancers of Childhood

122.

Molecular Biology of Childhood Cancers . . .1750Lee J. Helman and David Malkin

Tumor Suppressor Genes 1750

Retinoblastoma: The Paradigm 1752

Wilms Tumor: Three Distinct Loci 1753

Neurofibromatoses 1753

Neuroblastoma 1754

Ewing Sarcoma Family of Tumors 1755

Rhabdomyosarcoma 1755

Hereditary Syndromes Associated with Tumors of Childhood 1756

Malignant Rhabdoid Tumors 1757

Predictive Testing for Germ Line Mutations and Childhood

Cancers 1757

Molecular Therapeutics 1758

123.

Solid Tumors of Childhood . . . . . . . . . . . 1760Lisa L. Wang, Jason Yustein, Chrystal Louis, Heidi V. Russell,

Alberto S. Pappo, Arnold Paulino, Jed G. Nuchtern, and

Murali Chintagumpala

The Importance of Multidisciplinary Management Teams in Pediatric

Solid Tumors 1760

Neuroblastoma 1760

Wilms’ Tumor 1766

Retinoblastoma 1769

Pediatric Bone Sarcomas: Osteosarcoma and Ewing’s Sarcoma 1771

Rhabdomyosarcoma 1780

Liver Tumors 1784

Germ Cell Tumors 1786

124.

Childhood . . . . . . . . . . . . . . . . . . . . . . . . 1793

Leukemias and Lymphomas ofJudith F. Margolin, Karen R. Rabin, and David G. Poplack

Leukemias 1793

Lymphomas 1801

Supportive Care 1804

Long-Term, Palliative, and Hospice Care in Pediatric Oncology 1804

Section 12: Lymphomas in Adults

125.

Molecular Biology of Lymphomas . . . . . . 1806Urban Novak, Laura Pasqualucci, and Riccardo Dalla-Favera

The Cell of Origin of Lymphoma 1806

General Mechanisms of Genetic Lesion in Lymphoma 1807

Molecular Pathogenesis of B-Cell Non-Hodgkin’s Lymphoma 1810

Molecular Pathogenesis of T-Cell NHL 1816

Molecular Pathogenesis of HL 1817

126.

Hodgkin Lymphoma . . . . . . . . . . . . . . . . 1819Andreas Engert, Dennis A. Eichenauer, Nancy Lee Harris,

Peter M. Mauch, and Volker Diehl

History of Hodgkin Lymphoma 1819

Etiology and Epidemiology 1819

Biology and Cell of Origin 1820

Immunology of Hodgkin Lymphoma 1820

Diagnosis and Staging of Hodgkin Lymphomas 1825

Clinical Presentation of Hodgkin Lymphomas 1827

Treatment Methods for Hodgkin Lymphoma 1827

Choice of Treatment 1829

Treatment for Early Favorable Hodgkin Lymphoma 1832

Early Unfavorable Hodgkin Lymphoma 1834

Advanced Stages of Hodgkin Lymphoma 1836

Progressive and Relapsed Disease 1840

Lymphocyte-Predominant Hodgkin Lymphoma 1844

Special Populations 1846

Treatment-Related Late Side Effects 1848

Quality of Life 1850

New Drugs in Hodgkin Lymphoma 1851

127.

Non-Hodgkin Lymphomas . . . . . . . . . . . 1855Jonathan W. Friedberg, Peter M. Mauch, Lisa Rimsza, and

Richard I. Fisher

Epidemiology 1855

Etiology 1855

Biologic Background for Classification of Lymphoid Neoplasms 1857

B- and T-Cell Differentiation 1857

Immunophenotyping of Lymphoid Cells 1862

Chromosomal Translocations and Oncogene

Rearrangements 1863

Use of Immunophenotyping and Genetic Studies in the

Diagnosis of Lymphoid Neoplasms 1864

Principles of the World Health Organization Classification of

Lymphoid Neoplasms 1864

Principles of Management of Non-Hodgkin Lymphoma 1867

Specific Disease Entities 1869

Mature T-Cell and NK Cell Neoplasms 1884

Special Clinical Situations 1889

128.

Cutaneous Lymphomas . . . . . . . . . . . . . . 1894Francine M. Foss, Richard L. Edelson, and Lynn D. Wilson

Mycosis Fungoides and the Sézary Syndrome 1894

Diagnosis and Staging 1896

Clinical Evaluation of Patients with Cutaneous

Lymphoma 1898

Principles of Therapy of Mycosis Fungoides and the

Sézary Syndrome 1899

Systemic Therapy for Mycosis Fungoides and the

Sézary Syndrome 1902

Other Cutaneous Lymphomas 1905

129.

Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . 1908

Primary Central Nervous SystemLisa M. DeAngelis and Joachim Yahalom

Clinical Features 1908

Diagnostic Tests 1909

Pathology 1909

Management and Therapy 1910

Section 13: Leukemias and Plasma Cell Tumors

130.

Leukemias . . . . . . . . . . . . . . . . . . . . . . . . 1916

Molecular Biology of AcuteGlen D. Raffel and Jan Cerny

Leukemic Stem Cell 1916

Elucidation of Genetic Events in Acute Leukemia 1916

Recurring Chromosomal Abnormalities in Acute Leukemia 1917

Chromosomal Translocations that Target Core-

Binding Factor 1917

Chromosomal Translocations that Target the Retinoic

Acid Receptor Alpha Gene 1919

Chromosomal Translocations that Target HOX Family

Members 1920

Chromosomal Translocations that Target the

Chromosomal Translocations that Involve Transcriptional Coactivators

and Chromatin Remodeling Proteins 1921

MLL Gene 1920Contents

xliiit(1;22) Translocation Associated with Infant Acute

Megakaryoblastic Leukemia 1921

Deletions and Numeric Abnormalities in Acute Leukemias 1921

Chromosomal Translocations that Result in Overexpression of

Otherwise Normal Genes 1922

Chromosomal Translocations Involving the T-Cell Receptor 1922

Point Mutations in Acute Leukemia 1922

Mutation in Tumor Suppressor Genes 1924

Activating Mutations of NOTCH 1924

Mutations Altering Localization of NPM1 1925

Loss-of-Function Point Mutations in

Mutation of Lymphoid Development Genes in ALL 1925

Mutational Complementation Groups in Acute Leukemias 1925

Conclusion 1926

AML1,C/EBP, and GATA-1 1925131.

Management of Acute Leukemias . . . . . . 1928Partow Kebriaei, Richard Champlin, Marcos de Lima, and

Elihu Estey

Acute Myelogenous Leukemia 1929

Acute Lymphoblastic Leukemia 1946

132.

Leukemias . . . . . . . . . . . . . . . . . . . . . . . . 1955

Molecular Biology of ChronicAnupriya Agarwal, John C. Byrd, and Michael W. Deininger

Chronic Myeloid Leukemia 1955

Chronic Lymphocytic Leukemia 1958

133.

Chronic Myelogenous Leukemia . . . . . . . 1962Brian J. Druker and Stephanie J. Lee

Epidemiology 1962

Pathogenesis 1962

Diagnosis 1963

Clinical Course and Prognosis 1964

Treatment of Chronic Phase Disease 1965

Tyrosine Kinase Inhibitors 1965

Hematopoietic Cell Transplantation 1968

Advanced Phase Disease 1970

Future Directions 1971

134.

Chronic Lymphocytic Leukemias . . . . . . . 1973William G. Wierda and Susan O’Brien

Molecular Biology 1973

Immune Abnormalities 1975

Diagnosis 1975

Clinical Manifestations 1975

Treatment and Response Criteria 1977

New and Novel Agents for Treatment of Chronic Lymphocytic

Leukemia 1984

Second Malignancies and Transformation 1985

Prolymphocytic Leukemia 1985

Large Granular Lymphocyte Leukemia 1985

Hairy Cell Leukemia 1986

135.

Myelodysplastic Syndromes . . . . . . . . . . . 1988Stefan Faderl and Hagop M. Kantarjian

Epidemiology and Etiology 1988

Presentation and Diagnosis 1988

Cytogenetic-Molecular Abnormalities and MDS Pathogenesis 1990

Classification 1991

Therapy 1992

Outlook 1995

136.

Plasma Cell Neoplasms . . . . . . . . . . . . . . 1997Nikhil C. Munshi and Kenneth C. Anderson

History 1997

Epidemiology 1998

Etiology 1998

Pathogenesis 1999

Drug Resistance 2004

Clinical Manifestations 2005

Treatment 2015

Section 14: Other Cancers

137.

Cancer of Unknown Primary Site . . . . . . . 2033F. Anthony Greco and John D. Hainsworth

Pathologic Evaluation 2033

Clinical Features and Evaluation 2038

Treatment 2040

Special Issues in Carcinoma of Unknown Primary Site 2048

Unknown Primary Cancer in Children 2049

Future Directions and Changing Treatment Paradigm 2050

138.

Benign and Malignant Mesothelioma . . . 2052Harvey I. Pass, Nicholas J. Vogelzang, Steven M. Hahn, and

Michele Carbone

Mechanism of Asbestos-Carcinogenesis 2052

Overview of Molecular Mechanisms in Mesothelioma 2054

Alterations of Oncogenesin Mesothelioma 2054

Pathology of Mesothelioma 2056

Epidemiology and Clinical Presentation 2058

Diagnostic Approach for Presumed Mesothelioma 2062

Natural History 2064

Treatment 2066

Pleurectomy 2068

Radiotherapy for Mesothelioma 2069

Multimodality Treatment 2071

Novel Intrapleural Approaches: New Techniques with

New/Old Agents 2072

Chemotherapy and Newer Agents 2074

Novel Treatment Approaches 2076

Other Agents 2077

139.

Peritoneal Surface Malignancy . . . . . . . . . 2081Marcello Deraco, Dominique Elias, Olivier Glehen,

Cyril W. Helm, Paul H. Sugarbaker, and Vic J. Verwaal

Rationale for a Combined Treatment for Peritoneal Surface

Malignancy 2081

Validated Quantitative Prognostic Indicators 2081

Appendiceal Malignancy 2083

Colorectal Carcinomatosis: Curative Treatment and Prevention 2084

Diffuse Malignant Peritoneal Mesothelioma 2085

Gastric Cancer 2086

Peritoneal Carcinomatosis in Ovarian Cancer 2087

Sarcomatosis 2087

140.

Intraocular Melanoma . . . . . . . . . . . . . . . 2090Daniel M. Albert and Amol D. Kulkarni

Incidence and Etiology 2090

Anatomy and Pathology 2090

Diagnosis 2091

Metastatic Workup 2093

Staging 2093

Management 2093

Prognostic and Predictive Factors 2096

Posttreatment Quality of Life 2097

Section 15: Immunosuppression-Related

Malignancies

141.

AIDS-Related Malignancies . . . . . . . . . . . 2099Robert Yarchoan, Thomas S. Uldrick, and Richard F. Little

Cancer and HIV: Incidence and Etiology 2099

Kaposi Sarcoma 2101

KSHV-Associated Multicentric Castleman Disease 2104

AIDS-Associated Lymphomas 2104

Hodgkin’s Lymphoma 2110

HPV-Associated Cancer in HIV Infection 2110

Cervical Cancer 2110

Anal Cancer 2110

Future Directions 2111

xliv

Contents142.

Transplantation-Related Malignancies . . . 2113Smita Bhatia and Ravi Bhatia

Myelodysplasia and Acute Myeloid Leukemia 2113

Lymphomas 2119

Solid Tumors 2120

Section 16: Oncologic Emergencies

143.

Superior Vena Cava Syndrome . . . . . . . . . 2123Joachim Yahalom

Anatomy and Pathophysiology 2123

Etiology and Natural History 2123

Diagnostic Procedures 2124

Management 2125

Small Cell Lung Cancer 2125

Non–Small Cell Lung Cancer 2125

Non−Hodgkin’s Lymphoma 2125

Nonmalignant Causes 2126

Catheter-Induced Obstruction 2126

Treatment 2126

Areas of Uncertainty 2127

Recommendations 2128

144.

Increased Intracranial Pressure . . . . . . . . . 2130Kevin P. Becker and Joachim M. Baehring

Pathophysiological Considerations 2130

Epidemiology and Pathogenesis 2131

Clinical Presentation 2131

Diagnosis 2133

Treatment 2134

145.

Spinal Cord Compression . . . . . . . . . . . . 2136Kevin P. Becker and Joachim M. Baehring

Epidemiology 2136

Pathophysiology 2136

Clinical Presentation 2138

Differential Diagnosis 2138

Diagnosis 2139

Treatment 2139

Prognosis 2140

146.

Metabolic Emergencies . . . . . . . . . . . . . . 2142Antonio Tito Fojo

Tumor Lysis Syndrome 2142

Hyperuricemia 2144

Cancer and Hyponatremia 2147

Lactic Acidosis and Cancer 2148

Hypercalcemia and Cancer 2148

Cancer-Related Hemolytic Uremic Syndrome 2150

Section 17: Treatment of Metastatic Cancer

147.

Metastatic Cancer to the Brain . . . . . . . . 2153David A. Larson, James L. Rubenstein, Michael W. McDermott,

and Igor Barani

Brain Metastasis 2153

Carcinomatous Meningitis 2162

148.

Metastatic Cancer to the Lung . . . . . . . . . . . .2165King F. Kwong and Robert Timmerman

Rationale for Local Therapies for

Lung Metastases 2165

Modes of Metastatic Spread 2165

Diagnosis 2165

149.

Metastatic Cancer to the Liver . . . . . . . . . 2177H. Richard Alexander Jr., Jordan Berlin, and Fred Moeslein

Natural History of Liver Metastases 2177

Imaging of Liver Metastases 2179

Resection of Liver Metastases 2179

Results of Hepatic Resection for CRC 2180

Results of Resection for Noncolorectal Cancers 2181

Adjuvant Therapy for Resectable CRC Liver

Metastases 2181

Neoadjuvant Chemotherapy for CRC Liver Metastases 2183

Regional Therapies for Unresectable Isolated

Liver Metastases 2184

Radiation Therapy for Liver Metastases 2188

Conclusions 2190

150.

Metastatic Cancer to the Bone . . . . . . . . . 2192Edward Chow, Joel A. Finkelstein, Arjun Sahgal, and

Robert E. Coleman

Presentation 2192

Pathophysiology 2192

Diagnostic Evaluation 2192

Therapeutic Modalities 2193

New Targeted Therapies in the Treatment of Metastatic

Bone Disease 2194

External-Beam Radiation Therapy 2195

Systemic Radionuclides 2197

Radiotherapy for Complications of Bone Metastases: Localized

External Beam Radiotherapy for Pathological Fractures and

Spinal Cord Compression 2198

Mechanical Stability and Fracture Risk 2199

151.

the Pericardium . . . . . . . . . . . . . . . . . . . . 2205

Malignant Effusions of the Pleura andKing F. Kwong and Dao M. Nguyen

Malignant Pleural Effusion 2205

Malignant Pericardial Effusion 2209

152.

Malignant Ascites . . . . . . . . . . . . . . . . . . 2214Udai S. Kammula

Pathophysiology 2214

Diagnosis and Workup 2215

Treatment of Malignant Ascites 2216

153.

Paraneoplastic Syndromes . . . . . . . . . . . . 2220Michael Boyiadzis, Frank S. Lieberman, Larisa J. Geskin, and

Kenneth A. Foon

Endocrinologic Manifestations of Cancer 2220

Hematologic Manifestations of Cancer 2222

Renal Manifestations 2223

Cutaneous Manifestations of Cancer 2224

Disorders of Epidermal Proliferation and Keratinization

(Papulosquamous Disorders) 2224

Disorders of Cutaneous Discoloration and Deposition 2225

Neutrophilic Dermatoses 2226

Vascular Abnormalities 2226

Endocrine and Metabolic Disorders 2226

Bullous Disorders 2226

Collagen-Vascular Diseases 2227

Disorders of Hair 2227

Skin Neoplasms Associated with Internal Malignancy 2227

Miscellaneous Lesions 2229

Neurologic Manifestations of Cancer 2229

Limbic Encephalitis 2229

Autonomic Neuropathy 2231

Progressive Cerebellar Degeneration 2231

Paraneoplastic Visual Loss 2231

Opsoclonus-Myoclonus 2232

Paraneoplastic Motor Neuron Disorders 2232

Paraneoplastic Peripheral Neuropathies 2233

Neuromuscular Junction Disorders 2233

Contents

xlvParaneoplastic Syndromes with Muscle Rigidity 2234

Dermatomyositis 2234

Movement Disorders 2234

Approach to the Patient with Paraneoplastic

Neurologic Disease 2234

Section 18: Stem Cell Transplantation

154.

Autologous Stem Cell Transplantation . . . 2236John Magenau, Dale Bixby, and James Ferrara

History 2236

Stem Cell Mobilization 2236

Inadequate Mobilization of Stem Cells 2237

Tumor Contamination 2237

Indication and Timing of Autologous Hematopoietic Stem Cell

Transplantation 2237

Standard Infection Prophylaxis 2238

High-Dose Conditioning Regimens 2239

Complications of Autologous Hematopoietic Stem Cell

Transplantation 2239

Recent Developments in Autologous Hematopoietic Stem Cell

Transplantation 2241

Future Directions 2241

155.

Allogeneic Stem Cell Transplantation . . . . 2244Richard W. Childs

Conditioning Regimens 2244

Graft-Versus-Leukemia Effect 2245

Mechanisms of Graft-Versus-Leukemia Effect 2246

Complications of Allogeneic Hematopoietic Stem Cell

Transplantation 2247

Veno-Occlusive Disease 2247

Epstein-Barr Virus Lymphoproliferative Disorder 2248

Sources of Allogeneic Hematopoietic Stem Cells 2251

Results of Conventional Allogeneic Transplantation for

Hematologic Malignancies 2254

Future Prospects 2260

Section 19: Management of Adverse

Effects of Treatment

156.

Infections in the Cancer Patient . . . . . . . . 2262Juan Gea-Banacloche and Brahm H. Segal

RISK FACTORS FOR INFECTIONS IN

PATIENTS WITH CANCER AND ANTIMICROBIAL

PROPHYLAXIS 2262

Risk Factors for Infection 2262

Prevention of Infections 2266

DIAGNOSIS AND MANAGEMENT OF INFECTIOUS DISEASES

SYNDROMES 2272

Fever and Neutropenia 2272

SELECTED PATHOGENS OF INTEREST IN ONCOLOGY 2291

Selected Bacterial Infections in Patients with Cancer 2291

157.

Leukopenia and Thrombocytopenia . . . . . 2300Carla Kurkjian and Howard Ozer

Overview of Hematopoiesis and Hematopoietic

Growth Factors 2300

Erythropoietin 2300

Granulocyte Colony-Stimulating Factor 2301

Granulocyte-Macrophage Colony-Stimulating Factor 2304

Interleukin-11 2304

Thrombopoietin Agents 2305

Clinical Use of Erythropoietin-Stimulating Agents in

Cancer Therapy 2305

Clinical Use of Recombinant Granulocyte Colony-Stimulating

Factors in Cancer Therapy 2307

Use of Colony-Stimulating Factors in other Oncology Settings 2309

Clinical Use of Thrombopoietin Agents 2311

158.

Cancer-Associated Thrombosis . . . . . . . . . . .2314Agnes Y. Y. Lee and Alok A. Khorana

Mechanisms of Cancer-Associated Thrombosis 2314

Epidemiology of Cancer-Associated Thrombosis 2314

Prevention of Cancer-Associated Thrombosis 2316

Treatment of Cancer-Associated Thrombosis 2317

159.

Nausea and Vomiting . . . . . . . . . . . . . . . . 2321Elizabeth M. Blanchard and Paul J. Hesketh

Nausea and Vomiting Syndromes 2321

Pathophysiology of Treatment-Induced Nausea and Vomiting 2321

Defining the Risk of Nausea and Vomiting 2322

Antiemetic Agents 2323

Antiemetic Treatment by Clinical Setting 2326

Special Chemotherapy-Induced Nausea and Vomiting Problems 2326

Radiotherapy-Induced Nausea and Vomiting 2327

160.

Diarrhea and Constipation . . . . . . . . . . . . 2329Nathan I. Cherny

Diarrhea 2329

Constipation 2333

161.

Oral Complications . . . . . . . . . . . . . . . . . 2337Eliezer Soto, Jane M. Fall-Dickson, and Ann M. Berger

Oral Mucositis 2337

Chemotherapy-Induced Stomatitis 2337

Radiation-Induced Stomatitis 2337

Radiation Therapy-Related Complications 2338

Pathogenesis of Chemotherapy- and Radiation-Induced

Oral Mucositis 2338

Chronic Graft-Versus-Host Disease Oral Manifestations 2339

Sequelae of Oral Complications 2339

Strategies for Prevention and Treatment of Oral Complications 2340

Treatment Strategies 2340

Radioprotectors 2342

Biological Response Modifiers 2343

Treatment for Oral Chronic Graft-Versus-Host Disease 2344

Symptom Management 2345

162.

Pulmonary Toxicity . . . . . . . . . . . . . . . . . 2348Diane E. Stover and Robert J. Kaner

Radiation-Induced Pulmonary Toxicity 2348

Chemotherapy-Induced Pulmonary Toxicity 2351

163.

Cardiac Toxicity . . . . . . . . . . . . . . . . . . . . 2360Joachim Yahalom and Carol S. Portlock

Anthracyclines 2360

Cyclophosphamide 2362

Ifosfamide 2362

Taxanes 2362

Trastuzumab 2363

Fluoropyrimidines 2363

Tyrosine Kinase Inhibitors 2364

Radiation-Induced Heart Disease 2364

Future Directions 2367

164.

Hair Loss . . . . . . . . . . . . . . . . . . . . . . . . . . 2368Joyson J. Karakunnel and Ann M. Berger

Anatomy and Physiology 2368

Classification 2368

Diagnosis 2369

Treatment 2369

165.

Gonadal Dysfunction . . . . . . . . . . . . . . . . 2372John M. Norian, Eve C. Feinberg, Alan H. DeCherney, and

Alicia Y. Armstrong

Effects of Cytotoxic Agents on Adult Men 2372

Effects of Cytotoxic Agents on Adult Women 2374

xlvi

ContentsEffects of Cytotoxic Agents on Children 2378

Gonadal Dysfunction After Cranial Irradiation 2378

Preservation of Fertility, Hormone Levels, and

Sexual Function 2378

Pharmacologic Attempts at Preserving Fertility in Men 2382

Pharmacologic Attempts at Preserving Fertility in

Women 2382

Fertility Preservation in Women with Cervical Cancer 2384

Evaluation of Fertility After Treatment 2384

Hormone Replacement Therapy 2384

Prevention and Management of Erectile and Ejaculatory

Dysfunction 2384

Genetic Concerns 2385

166.

Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . 2387Sandra A. Mitchell and Ann M. Berger

Definition and Etiology of Cancer-Related Fatigue 2387

Current Theories of Cancer-Related Fatigue 2387

Evaluation of the Patient with Cancer-Related

Fatigue 2388

Interventions for Fatigue 2389

167.

Second Primary Cancers . . . . . . . . . . . . . . 2393Lois B. Travis, Smita Bhatia, James M. Allan,

Kevin C. Oeffinger, and Andrea Ng

Methods to Assess Second Cancer Risk 2393

Carcinogenicity of Individual Treatment Modalities 2394

Genetic Susceptibility to Second Primary Cancers 2396

Risk of Second Malignancy in Patients with Selected

Primary Cancers 2398

Pediatric Malignancies 2406

Comment 2409

168.

Neurocognitive Effects . . . . . . . . . . . . . . . 2411Paul D. Brown, Nadia N. I. Laack, and Jeffrey S. Wefel

Assessment of Neurocognitive Function 2411

Impact of Treatment 2412

Impact of Tumor 2415

Treatment of Cognitive Dysfunction 2415

169.

Cancer Survivorship . . . . . . . . . . . . . . . . . 2418Wendy Landier, Craig C. Earle, Smita Bhatia,

Melissa M. Hudson, Kevin Oeffinger, Patricia A. Ganz, and

Louis S. Constine

Definition of Survivorship and Scope of the Problem 2418

Goals of Survivorship Health Care 2419

Care Plans 2422

Delivery of Follow-Up Care and Best-Practice Models 2423

Educational Considerations 2423

Enhancing Research 2423

Survivorship Advocacy 2424

Section 20: Supportive Care and Quality of Life

170.

Management of Cancer Pain . . . . . . . . . . 2426Amy Abernathy and Kathleen M. Foley

Epidemiology 2426

Definition of Pain 2427

Common Pain Syndromes 2429

Management of Cancer Pain 2432

Psychological Approaches 2442

Anesthetic and Neurosurgical Approaches 2442

Neuropharmacologic Approaches 2445

Neuroablative and Neurostimulatory Procedures for the

Relief of Pain 2445

Trigger Point Injection and Acupuncture 2445

Physiatric Approaches 2446

Algorithm for Cancer Pain Management 2446

Future Directions 2446

171.

Nutritional Support . . . . . . . . . . . . . . . . . 2448Alessandro Laviano, Robert A. Meguid, and

Michael M. Meguid

Anorexia 2448

Changes in Host Metabolism: Weight Loss and

Cachexia 2449

Nutrition Therapy for Cancer Cachexia 2450

Nutrition and Tumor Growth 2450

Nutritional Assessment of the Cancer Patient 2451

Parenteral Versus Enteral Nutrition in

Cancer Patients 2451

Ethical and Legal Aspects of Nutrition Therapy 2454

172.

Sexual Problems . . . . . . . . . . . . . . . . . . . . 2456Veronica Sanchez Varela, Christian J. Nelson, and

Sharon L. Bober

Cancer in Men 2456

Cancers that Affect Men and Women 2458

Cancer in Women 2460

Cancer in Children and Young Adults 2463

Relevant Sociocultural Considerations 2463

Disruption of Intimacy and Relational

Considerations 2464

173.

Psychological Issues in Cancer . . . . . . . . . 2467David Spiegel and Michelle B. Riba

Understanding Cancer as a Trauma 2467

Common Psychiatric Conditions 2467

Screening for Psychological Problems 2467

Coping 2469

Treatment Interventions 2469

Outcome 2472

Implications for Cancer Progression and

Mortality 2472

Survivorship 2472

Psychotropic Medication 2473

174.

Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . 2477

Communicating News to the CancerEric J. Cassell

Preventing Illness 2477

Communication 2477

Explanations 2478

Uncomfortable Questions 2479

Information 2479

Meaning 2479

Cafeteria Explanations 2480

175.

Specialized Care of the Terminally Ill . . . . 2481Kristen G. Schaefer, Kathy Selvaggi, and Janet L. Abrahm

Discussing Prognosis 2481

Discussing End of Life 2481

Hope 2482

Healing Versus Curing 2482

How to Tell the Children 2482

Cultural and Religious Considerations 2482

Care without Chemotherapy 2483

Palliative Care Programs 2483

Hospice Programs 2483

Relief of Suffering 2483

The Final Days 2488

After the Death 2488

Grief and Bereavement 2488

176.

Community Resources . . . . . . . . . . . . . . . 2491Bonnie A. Indeck and Nora Rightmer

Community Resources for the Cancer Patient and Family 2491

The Cancer Patient 2491

Social and Emotional Support 2491

Informational Support 2492

Contributing Authors

xlviiInstrumental Support 2493

Common Community Resources 2493

Internet Resources 2496

Language Resources 2498

Legal Resources 2498

Palliative Care 2498

Personal Websites that Facilitate Communication 2498

Survivorship 2498

Transportation 2498

Wish Foundations 2499

177.

Rehabilitation of the Cancer Patient . . . . 2500Michael D. Stubblefield

The Rehabilitation Team 2500

Complications of Cancer and its Treatment 2501

Neuromuscualr Complications of Cancer and Cancer Treatment 2503

Musculoskeletal Complications of Cancer and Cancer

Treatment 2510

Radiation Fibrosis Syndrome 2513

Lymphedema 2518

Rehabilittion Interventions 2519

Nonpharmacologic Pain Management 2521

Section 21: Societal Issues in Oncology

178.

Regulatory Issues . . . . . . . . . . . . . . . . . . . 2523Ann T. Farrell, Grant A. Williams, and Richard Pazdur

The History of Food and Drug Administration Regulation of

Drugs and Biologics 2523

Food and Drug Administration Oversight of Clinical Trials for

Drugs and Biologics 2523

The Basis for Cancer Drug Approval 2525

Drug Safety Reporting and Evaluation 2527

Expanded Access to Investigational Drugs 2527

Regulation of Devices for Cancer Treatment and Diagnosis 2528

179.

Health Disparities in Cancer . . . . . . . . . . 2532Harold P. Freeman

Race and Cancer 2534

Relationships Between Culture and Cancer 2535

Poverty as a Cause of Cancer Disparities 2535

Patient Navigation 2535

The Harlem Breast Cancer Experience 2536

Discussion 2538

What Must be Done to Diminish Cancer Disparities 2538

180.

Cancer Information on the Internet . . . . . 2540Sherri L. Place and J. Robert Beck

Background 2540

Tools for Finding Information 2540

Evaluating Information 2541

Search Strategies 2543

Useful Tools for Keeping Up 2544

Section 22: Complementary, Alternative, and

Integrative Therapies

181.

Therapies in Cancer Care . . . . . . . . . . . . . 2550

Complementary, Alternative, and IntegrativeCatherine Ulbricht, Lorenzo Cohen, and Richard Lee

Background 2550

Establishing an Integrative Oncology Approach with Patients 2550

Standardization and Quality 2555

Specific Complementary and Alternative Medicine

Therapies 2556

Index 2563

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