فهرست کتاب دیویتا:
Contributing Authors v ■ Preface xvii ■ Acknowledgements xviii
P A R T I
Etiology and Prevention
of Cancer
1. Global Cancer Incidence and Mortality . 2
Hyuna Sung and Ahmedin Jemal
Introduction 2
Data Sources 2
Measures of Burden 3
Measures of Risk 3
Demographic Factors that Affect Cancer Risk 4
Global Patterns of Cancer Risk and Burden 9
Patterns of Most Common Cancers 12
Issues in Interpreting Temporal Trends 23
Future Burden of Cancer 24
Conclusion 26
2. Tobacco Use and the Cancer Patient . 30
Graham W. Warren and Vani N. Simmons
Introduction 30
Tobacco Use Epidemiology, Addiction, and Tobacco Product
Evolution 30
Electronic Nicotine Delivery Systems, or Electronic
Cigarettes 31
Defining Tobacco Use by the Cancer Patient 31
Epidemiology of Tobacco Use and Cessation by Cancer
Patients 32
Smoking Cessation in the Context of Lung Cancer
Screening 32
The Clinical Effects of Smoking and Cessation on Cancer
Treatment Outcomes 33
Addressing Tobacco Use by the Cancer Patient 34
Research Considerations and the Future of Addressing Tobacco
Use Across the Continuum of Cancer Care 40
3. Lifestyle Factors. 43
Justin C. Brown, Tracy E. Crane, Jeffrey A. Meyerhardt,
and Jennifer A. Ligibel
Introduction 43
Obesity 43
Physical Activity 46
Nutrition 48
Mechanistic Data 51
Lifestyle Guidelines for Cancer Prevention and Control 51
Conclusion 51
4. Genetic Counseling & Testing. 54
Danielle C. Bonadies, Meagan B. Farmer, and Ellen T. Matloff
The Oncology Genetic Testing Landscape 54
The Evolving Role of Genetic Counselors 54
Responsibly Scaling Genetic Services 54
Practical Guidance for Ordering and Interpreting Genetic
Testing 55
Additional Issues in Cancer Genetic Counseling 57
Conclusion 58
P A R T I I
Cancer Therapeutics
5. Essentials of Radiation Therapy. 62
Randall K. Ten Haken and Theodore S. Lawrence
Introduction 62
Radiation Physics 62
Treatment Planning 66
Other Treatment Modalities 67
Treatment Intent 70
Fractionation 71
Adverse Effects 72
Principles of the Use of Agents that Modify the Radiation
Response 73
6. Alkylating Agents. 76
Kenneth D. Tew
Historical Perspectives 76
Chemistry 76
Classification 76
Clinical Pharmacokinetics/Pharmacodynamics 81
Therapeutic Uses 82
Toxicities 82
Complications with High-Dose Alkylating Agent Therapy 84
Alkylating Agent–Steroid Conjugates 84
Drug Resistance and Modulation 85
Future Perspectives 85
7. Platinum Analogs. 88
Jan H. Beumer, Fabienne Thomas, and Étienne Chatelut
Introduction 88
History 88
Platinum Chemistry 88
Platinum Complexes after Cisplatin 88
xx Contents
Mechanisms of Action and Cellular Effects 90
Combinatorial Efforts 93
Clinical Pharmacology 94
8. Antimetabolites. 98
Chaoyuan Kuang and Edward Chu
Antifolates 98
5-Fluoropyrimidines 101
Capecitabine 102
Trifluridine/Tipiracil 103
Cytarabine 103
Gemcitabine 104
6-Thiopurines 105
Fludarabine 105
Cladribine 106
Clofarabine 106
Nelarabine 107
9. Topoisomerase-Interacting Agents. 109
Anish Thomas, Khanh T. Do, Shivaani Kummar,
and Yves Pommier
Biochemical and Biological Functions of Topoisomerases 109
Topoisomerase Inhibitors as Interfacial Poisons 110
Topoisomerase I Inhibitors: Camptothecins and Beyond 111
Topoisomerase II Inhibitors: Intercalators and
Nonintercalators 114
Tumor-Targeted Topoisomerase Inhibitors 118
Topoisomerase I Inhibitor Combinations 119
Determinants of Response to Topoisomerase Inhibitors 119
10. Microtubule Inhibitors. 123
Christopher J. Hoimes
Microtubules 123
Taxanes 123
Vinca Alkaloids 127
Microtubule Antagonists and ADC Payloads 129
Antimicrotubule Payloads of Antibody Drug Conjugates 129
Mitotic Motor Protein Inhibitors 130
Mechanisms of Resistance to Microtubule Inhibitors 130
11. Kinase Inhibitors as Anticancer Drugs. 133
Aphrothiti J. Hanrahan, Gopa Iyer, Debyani Chakravarty,
and David B. Solit
Introduction 133
Validating Mutated Kinases as Cancer Drug Targets—the
Development of Imatinib for Patients with Chronic
Myelogenous Leukemia and Gastrointestinal Stromal
Tumors 137
The Development of HER2-Targeted Therapies in Breast and
Other Cancers 139
The Development of EGFR Tyrosine Kinase Inhibitors in Lung
Cancer 139
Identifying Therapeutic Targets in EGFR Wild-Type Lung
Cancers 140
Targeting BRAF-Mutant Tumors with RAF and MEK
Inhibitors 142
PI3 Kinase Pathway Inhibitors 144
FGFR Inhibitors: an Important Case for Isoform Selectivity 145
One Target or Several: Multitargeted Kinase Inhibitor
Therapy 146
CDK4/6 Inhibitors 146
Bruton Tyrosine Kinase Inhibitors—An Example of Lineage
Dependence 146
Tumor Agnostic Drug Targets—TRK Inhibitors for NTRK
Fusion Positive Cancers 147
Future Directions 147
12. Histone Deacetylase Inhibitors,
Demethylating Agents, and
Epigenetic Drugs. 151
Chaoyuan Kuang, James G. Herman, and Edward Chu
Introduction 151
The Cancer Epigenome 151
Histone Deacetylase Inhibitors 156
Other Epigenetic Drugs 157
13. Proteasome Inhibitors. 159
Vikas A. Gupta, Nisha S. Joseph, Ajay K. Nooka, and
Lawrence H. Boise
Biochemistry of the Ubiquitin-Proteasome Pathway 159
Proteasome Inhibitors 159
Proteasome Inhibitors in Cancer 160
14. Poly(ADP-Ribose) Polymerase Inhibitors
for Tumors with Defects in DNA Repair. 173
Alan Ashworth
Introduction 173
Cellular DNA Repair Pathways 173
BRCA1 and BRCA2 Mutations and DNA Repair 173
The Development of PARP Inhibitors 174
PARP-1 Inhibition as a Synthetic Lethal Therapeutic Strategy for
the Treatment of BRCA-Deficient Cancers 174
Early Clinical Results Testing Synthetic Lethality of PARP
Inhibitors and BRCA Mutation 174
Clinical Studies Leading to the Approval of PARP Inhibitors for
Therapeutic Use 175
The Use of PARP Inhibitors in Non-BRCA Germline Mutant
Cancers 175
Mechanisms of Resistance to PARP Inhibitors 176
Future Prospects 176
Disclosure 176
15. Miscellaneous Chemotherapeutic Agents. 178
Mehmet Sitki Copur, Amber Rupe, and Jacqueline R. Kelly
Omacetaxine 178
Hydroxyurea 178
Mitotane 178
Arsenic Trioxide 179
Bleomycin 179
Mitomycin-C 179
Procarbazine 180
l-Asparaginase 180
Sirolimus, Temsirolimus, Everolimus 180
Thalidomide, Lenalidomide, Pomalidomide 181
Miscellaneous Agents Repurposable for Cancer Therapy 182
Cardiovascular Drugs Repurposable for Cancer
Therapy 182
Antimicrobial Drugs Repurposable for Cancer Therapy 185
Antidiabetic Drugs Repurposable for Cancer Therapy 186
16. Hormonal Agents. 191
Ciara C. O’Sullivan, Akeem R. Lewis, and Matthew P. Goetz
Introduction 191
Selective Estrogen Receptor Modulators 191
Aromatase Inhibitors 193
Resistance to Endocrine-Targeted Therapy in Breast Cancer 194
Gonadotropin-Releasing Hormone Analogs 196
Antiandrogens 197
Resistance to Androgen Therapies in Prostate Cancer 198
Other Sex Steroid Therapies 198
Other Hormonal Therapies 199
Contents xxi
17. Immunotherapy Agents: Monoclonal
Antibodies . 202
Allison Fitzgerald, Rachael Maynard, David Zahavi,
and Louis M. Weiner
Introduction 202
Immunoglobulin Structure 202
Factors Regulating Antibody-Based Tumor Targeting 202
Unconjugated Antibody Mechanisms of Action 204
Conjugated Antibodies 204
Antibody Modifications to Enhance Efficacy 205
Antibodies Approved for Use in Solid Tumors 206
Antibodies Approved for Use in Hematologic Malignancies 208
Conclusion 210
18. Immunotherapy Agents: Checkpoint
Modulators. 212
Jeffrey S. Weber and Mario Sznol
Introduction 212
Preclinical Work with CTLA-4 212
Early Studies with CTLA-4 Antibodies in Metastatic Cancer 212
Adjuvant Trials of IPI 213
Preclinical Work with PD-1 213
Early Studies with PD-1 Antibodies in Metastatic Cancer 214
Adjuvant Trials of Nivolumab and Pembrolizumab 215
Neoadjuvant Trials of Nivolumab and Pembrolizumab in
Melanoma and Other Cancers 215
Immune Checkpoint Inhibitor Combinations 216
19. Immunotherapy Agents:
Cellular Therapies . 222
Stephanie L. Goff and Nirali N. Shah
Introduction 222
Tumor Infiltrating Lymphocytes (TIL) 223
Chimeric Antigen Receptor (CAR) T-Cells 227
T-Cell Receptor Engineered T Cells (TCR) 230
Other Potential Cellular Therapies 231
20. Immunotherapy Agents: Nonspecific
Stimulators. 235
Douglas B. Johnson and Jeffrey A. Sosman
Role in the Tumor Microenvironment 235
IL-2 Variant Molecules—Improving the Safety and Efficacy of
High-Dose IL-2 235
Antibody-Cytokine Fusion (Immunocytokines) 237
Oncolytic Viruses 237
Talimogene Laherparepvec 237
Other Oncolytic Viruses 238
Clinical Application 238
Toll-Like Receptor Agonists 239
Sting Agonists 239
T-Cell Activators 239
4-1BB (CD137) 239
GITR (Glucocorticoid-Induced TNF-R-Related Protein) 239
ICOS (Inducible T-Cell Costimulator) 240
OX40 240
CD40 240
Cytokines Other Than IL-2 240
21. Allogeneic Stem Cell Transplantation. 242
Scott Nicholas Furlan and Geoffrey R. Hill
Introduction 242
Conditioning Regimens 242
Hematopoietic Stem and Progenitor Cell Sources 243
Immunobiology of Transplantation 245
Complications of Allogeneic Stem Cell Transplantation and
Their Management 248
Graft Failure 251
Major Disease Indications for Allogeneic Stem Cell
Transplantation 252
Prevention and Treatment of Posttransplant Relapse 253
Future Directions 253
P A R T I I I
Practice of Oncology
22. Design and Analysis of Clinical Trials. 260
Richard M. Simon
Introduction 260
Phase I Clinical Trials 260
Phase II Clinical Trials 261
Design of Phase III Clinical Trials 266
Factorial Designs 268
Analysis of Phase III Clinical Trials 270
Reporting Results of Clinical Trials 273
False-Positive Reports in the Literature 273
Meta-Analysis 273
SECTION 1. HEAD AND NECK
23. General Principles in the Management
of Head and Neck Cancer. 276
William M. Mendenhall, Peter T. Dziegielewski, and
Lara A. Dunn
Incidence and Etiology 276
Anatomy and Pathology 276
Diagnosis 276
Staging 277
Principles of Treatment for Squamous Cell Carcinoma 278
Management 279
Clinically Negative Neck 279
Clinically Positive Neck Lymph Nodes 280
Chemotherapy 280
24. Cancer of the Nasopharynx . 287
Melvin Lee Kiang Chua, Matt Lechner, and Brigette B.Y. Ma
Epidemiology and Etiology 287
Genetic Risk Factors and Pathogenetic Mechanisms 287
Diagnostic Workup and Screening 287
Staging 288
Clinical and Molecular Biomarkers 289
Treatment of Early-Stage Disease 290
Treatment of Locoregionally Advanced Disease 290
Radiotherapy Delivery, Planning, and Dose Fractionation 291
Post-Treatment Surveillance 291
Treatment of Recurrent or Metastatic Disease 292
25. Cancer of the Larynx and Hypopharynx. 297
William M. Mendenhall, Peter T. Dziegielewski, and
Lara A. Dunn
Introduction 297
Larynx 297
Hypopharynx: Pharyngeal Walls, Pyriform Sinus, and
Postcricoid Pharynx 302
xxii Contents
26. Oropharynx Cancer. 307
Michelle L. Mierzwa, Keith A. Casper, and Paul L. Swiecicki
Pathophysiology of HPV-Positive Versus HPV-Negative OPSCC 307
Anatomy 307
Workup 308
Staging 309
General Principles for Selection of Treatment 309
Management 310
Management of Recurrence 311
Cancer Surveillance 313
Survivorship 314
27. Cancer of the Oral Cavity. 318
Peter T. Dziegielewski, William M. Mendenhall, and Lara A. Dunn
Introduction 318
Epidemiology 318
Risk Factors 318
Workup and Staging 318
Lip 319
Floor of the Mouth 320
Oral Tongue 322
Buccal Mucosa 323
Gingiva and Hard Palate (Including Retromolar Trigone) 324
Neck Treatment 326
28. Cancer of the Nasal Vestibule, Nasal Cavity,
and Paranasal Sinuses . 330
Steven J. Frank, Renata Ferrarotto, and Ehab Y. Hanna
Anatomy 330
Pathology 330
Patterns of Spread 331
Clinical Picture 332
Staging 332
Treatment 332
29. Cancer of the Salivary Gland. 338
Bhishamjit S. Chera, Jose Zevallos, and Glenn J. Hanna
Introduction 338
Anatomy 338
Epidemiology 339
Clinical Presentation 339
Diagnostic Workup and Staging 339
Staging 340
Pathological Classification 340
Prognostic Factors and Molecular Markers 341
Treatment 341
Treatment Outcomes 347
Surveillance and Suvivorship 347
SECTION 2. THORACIC CAVITY
30. Non–small-cell Lung Cancer. 349
Daniel Morgensztern, Frank C. Detterbeck, Alexander Drilon,
Sara B. Goldberg, Henry S. Park, Katerina Politi, Kurt A. Schalper,
Lynn T. Tanoue, and Roy S. Herbst
Epidemiology and Risk Factors 349
Clinical Manifestations, Diagnosis, and Staging 349
Pathology 355
Molecular Landscape of Non–small-cell Lung Cancer 362
Treatment of Patients with Stage I to III 363
Treatment of Stage IV 368
Stage IV Non–small-cell Lung Cancer Without Driver
Alterations 378
Oligometastases 381
Malignant Pleural Effusion 382
Conclusion 383
31. Small Cell and Neuroendocrine Tumors
of the Lung. 391
Christine L. Hann, Benjamin J. Drapkin, Abraham J. Wu,
Natasha Rekhtman, John D. Minna, and Charles M. Rudin
Introduction 391
Small Cell Lung Cancer 391
Typical Carcinoid and Atypical Carcinoid Tumors 407
Large Cell Neuroendocrine Carcinoma 411
32. Neoplasms of the Mediastinum. 423
Robert B. Cameron, Nicolas Girard, and Percy P. Lee
Thymic Neoplasms 423
Germ Cell Tumors 434
SECTION 3. GI TRACT
33. Cancer of the Esophagus . 439
Karyn A. Goodman, Mitchell C. Posner, and David H. Ilson
Introduction 439
Epidemiology 439
Etiologic Factors and Predisposing Conditions 440
Applied Anatomy and Histology 442
Natural History and Patterns of Failure 443
Clinical Presentation 444
Diagnostic Studies and Pretreatment Staging Tools 444
Staging Guidelines 445
Biomarkers 445
Treatment 447
Predictors of Treatment Response 464
Palliation of Esophageal Cancer with Radiation Therapy 466
Radiotherapy Techniques 467
Treatment of Metastatic Disease 469
34. Cancer of the Stomach. 487
Einat Shacham-Shmueli, Ofer Margalit, Aviram Nissan,
Alexander Stojadinovic, Yaacov Richard Lawrence,
and Itzhak Avital
Incidence and Epidemiology 487
Etiology and Risk Factors 487
Anatomic Considerations 488
Patterns of Spread 488
Histopathology 490
Molecular Classification 490
Clinical Presentation 491
Pretreatment Evaluation 491
Staging 492
Localized Disease 493
Adjuvant and Neoadjuvant Therapy 496
Treatment of Advanced Disease (Stage IV) 499
Gastric Cancer in the Elderly 503
Palliative Measures for Advanced Disease 503
35. Cancer of the Pancreas. 509
Lee M. Ocuin, Jordan M. Winter, Jonathan R. Brody,
James A. Posey III, Adam C. Mueller, and Charles J. Yeo
Incidence and Etiology 509
Anatomy and Pathology 510
Exocrine Pancreatic Cancers 510
Endocrine Pancreatic Cancers 514
Pancreatic Ductal Adenocarcinoma: Screening 515
Pancreatic Ductal Adenocarcinoma: Diagnosis 515
Contents xxiii
Pancreatic Ductal Adenocarcinoma: Staging and Assessment
of Resectability 516
Clinically Resectable Pancreatic Ductal Adenocarcinoma 520
Clinically Borderline Resectable Pancreatic Ductal
Adenocarcinoma 528
Clinically Locally Advanced Pancreatic Ductal
Adenocarcinoma 530
Stage IV: Metastatic Pancreatic Ductal Adenocarcinoma 532
Future Directions and Challenges 536
Conclusions 537
36. Cancer of the Liver . 544
Yuman Fong, Anne M. Covey, Mary Feng, and Daneng Li
Introduction 544
Epidemiology 544
Etiologic Factors 544
Diagnosis 545
Staging 546
Molecular and Biomarker 546
Treatment of Hepatocellular Carcinoma 548
Adjuvant and Neoadjuvant Therapy 551
Treatment of Other Primary Liver Tumors 564
37. Cancer of the Biliary Tree. 570
Tushar Patel, Kabir Mody, and Sunil Krishnan
Introduction 570
Anatomy of the Biliary Tract 570
Cholangiocarcinoma 571
Gallbladder Cancer 581
Systemic Therapy for Cholangiocarcinoma 585
38. Small Bowel Cancer . 590
Ronald Chamberlain, Nasrin Ghalyaie, and Sachin Patil
Introduction 590
Small Bowel Adenocarcinoma 594
Carcinoid Tumors 597
Small Bowel Lymphoma 599
Gastrointestinal Stromal Tumor 600
Metastatic Cancer to the Small Bowel 600
39. Gastrointestinal Stromal Tumor. 604
Paolo G. Casali, Angelo Paolo Dei Tos, and Alessandro Gronchi
Introduction 604
Incidence and Etiology 604
Anatomy and Pathology 604
Screening 607
Diagnosis 607
Staging 608
Management by Stage 608
Palliative Care 614
40. Cancer of the Colon. 618
Steven K. Libutti, Leonard B. Saltz, Christopher G. Willett,
and Rebecca A. Levine
Introduction 618
Molecular Biology 618
Multistep Models of Colorectal Cancer and Genetic Instability 618
Mutational and Epigenetic Landscapes in Colorectal Cancer 618
Oncogene and Tumor Suppressor Gene Mutations in Colorectal
Cancer Progression 620
Epidemiology 621
Etiology: Genetic and Environmental Risk Factors 622
Familial Colorectal Cancer 625
Anatomy of the Colon 627
Diagnosis of Colorectal Cancer 628
Screening for Colorectal Cancer 629
Staging and Prognosis of Colorectal Cancer 630
Approaches to Surgical Resection of Colon Cancer 637
Surgical Management of Complications From Primary Colon
Cancer 639
Laparoscopic Colon Resection 640
Polyps and Stage I Colon Cancer 641
Stage II and Stage III Colon Cancer 641
Treatment of Stage II Patients 644
Treatment Options for Stage III Patients 647
Investigational Adjuvant Approaches 648
Follow-Up After Management of Colon Cancer with Curative
Intent 649
Surgical Management of Stage IV Disease 651
Management of Unresectable Metastatic Disease 651
Molecular Predictive Markers 667
41. Cancer of the Rectum . 678
Steven K. Libutti, Christopher G. Willett, Leonard B. Saltz,
and Rebecca A. Levine
Introduction 678
Anatomy 678
Staging 679
Surgery 681
Does Adjuvant Radiation Therapy Impact Survival? 690
Preoperative Radiation Therapy 690
Which Patients Should Receive Adjuvant Therapy? 692
Support of Nonoperative Management 694
Total Neoadjuvant Therapy 694
Concurrent Chemotherapy 697
Synchronous Rectal Primary and Metastases 699
Management of Unresectable Primary and Locally Advanced
Disease (T4) 699
Management of Locally Recurrent Disease 700
Re-Irradiation in Recurrent Disease 700
Radiation Therapy Technique 701
Radiation Fields 701
42. Cancer of the Anal Region . 708
Brian G. Czito, Kayla Weiss Miranda, Christina Huang,
Matthew F. Kalady, and Cathy Eng
Introduction 708
Epidemiology and Etiology 708
Screening and Prevention 709
Clinical Presentation and Staging 713
Prognostic Factors 713
Treatment of Localized Squamous Cell Carcinoma 715
Treatment of Other Sites and Pathologies 723
SECTION 4. CANCERS OF THE GU TRACT
43. Cancer of the Kidney. 729
Andres F. Correa, Brian I. Rini, W. Marston Linehan,
Laura S. Schmidt, Brian R. Lane, and Robert G. Uzzo
Introduction 729
Epidemiology, Demographics, and Risk Factors 729
Pathology of Renal Cell Carcinoma 729
Differential Diagnosis and Staging 731
Hereditary Kidney Cancer Syndromes, Genetics, and Molecular
Biology 732
Treatment of Localized Renal Cell Carcinoma 738
Treatment of Locally Advanced Renal Cell Carcinoma 742
Surgical Management of Advanced Renal Cell Carcinoma 746
Systemic Therapy for Advanced Renal Cell Carcinoma 748
Conclusion and Future Directions 750
Acknowledgments 751
xxiv Contents
44. Cancer of the Bladder, Ureter,
and Renal Pelvis. 756
Adam S. Feldman, Richard J. Lee, David T. Miyamoto,
Douglas M. Dahl, and Jason A. Efstathiou
Introduction 756
Epidemiology 756
Screening and Early Detection 756
Pathology 757
Molecular Biology of Bladder Cancer and Biomarkers 757
Cancer of the Bladder 759
Cancers of the Renal Pelvis and Ureter 775
45. Cancer of the Prostate. 784
Zachary R. Reichert, Leonardo Kayat Bittencourt, Aaron M. Udager,
Ganesh S. Palapattu, and Daniel E. Spratt
Introduction 784
Epidemiology 784
Anatomy and Pathology 786
Screening 791
Diagnosis and Workup 792
Risk Stratification 803
Treatment of Prostate Cancer 806
Management of Clinical Disease States 815
Future Directions 832
46. Cancer of the Urethra and Penis . 846
J. Ryan Mark, Mark D. Hurwitz, Leonard G. Gomella,
and W. Kevin Kelly
Introduction 846
Urethral Cancer in Men 846
Urethral Cancer in the Female 848
Penile Cancer 849
47. Cancer of the Testis. 856
Matthew T. Campbell, Jose A. Karam, and
Christopher J. Logothetis
Introduction 856
Incidence and Epidemiology 856
Initial Presentation and Management 856
Histology 857
Biology 859
Immunohistochemical Markers 860
Staging 860
Management of Clinical Stage I Disease 862
Management of Clinical Stage II Disease (Low Tumor
Burden) 864
Management of Stage II Disease with High Tumor Burden and
Stage III Disease 865
Management of Recurrent Disease 867
Treatment Sequelae 868
Long-Term Follow-Up 869
Midline Tumors of Uncertain Histogenesis 869
Other Testicular Tumors 869
SECTION 5. GYNECOLOGICAL CANCERS
48. Cancer of the Cervix . 874
Kirsten Jorgensen, Jose Alejandro Rauh-Hain, and Ann H. Klopp
Epidemiology 874
Prevention 876
Pathology 876
Clinical Manifestations 879
Clinical Evaluation and Staging 880
Prognostic Factors 881
Chemotherapy Followed by Radical Surgery 881
Management of Abnormal Cervical Screening 882
Treatment of Invasive Disease 882
49. Cancer of the Vagina and Vulva . 902
Hima Bindu Musunuru, John Austin Vargo, Alexander B. Olawaiye,
and Sushil Beriwal
Carcinoma of the Vagina 902
Carcinoma of the Vulva 906
50. Cancer of the Uterine Body. 917
Kaled M. Alektiar, Nadeem R. Abu-Rustum, and Vicki Makker
Endometrial Carcinoma 917
Uterine Sarcomas 928
51. Gestational Trophoblastic Neoplasia . 935
Ross S. Berkowitz, Kevin M. Elias, and Neil S. Horowitz
Introduction 935
Incidence 935
Genetics, Pathology, and Natural History 935
Indications for Treatment 935
Measurement of Human Chorionic Gonadotropin 935
Pretreatment Evaluation 936
Staging and Prognostic Score 936
Treatment 937
Placental Site or Epithelioid Trophoblastic Tumors 938
Subsequent Pregnancy after Treatment for Gestational
Trophoblastic Neoplasia 939
52. Ovarian Cancer . 941
Krishnansu S. Tewari, Richard T. Penson, and Bradley J. Monk
Incidence and Etiology 941
Anatomy and Pathology 942
Screening and Prevention 943
Diagnosis 944
Presentation and Evaluation of Advanced Disease 946
International Federation of Gynecology and Obstetrics
Staging 946
Management by Stage 947
Management of Newly Diagnosed Advanced-Stage Disease 949
Maintenance Targeted Therapy 954
Maintenance Therapy using PARP Inhibitors 954
Clinical Implications of BRCA1/2 Mutation Status 954
BRCA1/2 Reversion Mutations 958
Tolerability of PARP Inhibitors 958
Management of Recurrent Disease 959
Antiangiogenesis Therapy for Treatment of Recurrent Disease 961
Immunotherapy 961
Randomized Trials of Immune Checkpoint Inhibitors 962
Therapeutic Vaccines 963
Toll-Like Receptors 963
Oncolytic Viruses 963
Chimeric Antigen Receptors 963
Bispecific T-Cell Engagers 964
Immune-Mediated Toxicity 964
Immune-Related Response Criteria 964
Palliative Care 964
SECTION 6. BREAST CANCER
53. Malignant Tumors of the Breast. 968
Reshma Jagsi, Tari A. King, and Harold J. Burstein
Incidence and Etiology 968
Screening and Prevention for Women at High Risk of Breast
Cancer 970
Anatomy and Pathology 971
Diagnosis and Biopsy 975
Contents xxv
Staging 976
Management by Stage: Ductal Carcinoma in Situ 976
Management by Stage: Primary Operable Invasive Breast
Cancer 982
Management by Stage: Adjuvant Systemic Therapy 993
Management by Stage: Special Considerations 999
Management by Stage: Metastatic Disease 1003
Acknowledgment 1007
SECTION 7. CANCER OF THE ENDOCRINE
SYSTEM
54.Thyroid Tumors. 1019
Anupam Kotwal and Geoffrey B. Thompson
Anatomy and Physiology 1019
Thyroid Nodules 1019
Thyroid Tumor Classification and Staging Systems 1020
Differentiated Thyroid Cancer 1022
Treatment of Differentiated Thyroid Cancer 1023
Anaplastic Thyroid Cancer 1026
Medullary Thyroid Cancer 1026
Thyroid Lymphoma 1028
Thyroid Cancer in Children 1028
55. Parathyroid Tumors. 1032
Anupam Kotwal and Geoffrey B. Thompson
Incidence and Etiology 1032
Anatomy and Pathology 1032
Clinical Manifestations and Screening 1033
Diagnosis 1033
Staging 1034
Management of Parathyroid Carcinoma 1034
Follow-Up and Natural History 1036
Prognosis 1036
56. Adrenal Tumors . 1038
Antonio Marcondes Lerario, Dipika R. Mohan, Shruti Jolly,
Tobias Else, and Gary D. Hammer
Introduction 1038
Incidence and Etiology 1038
Anatomy and Pathology 1038
Screening 1040
Diagnosis 1040
Staging 1043
Management 1043
Palliative Care 1045
57. Pancreatic Neuroendocrine Neoplasms. 1048
James C. Yao, Callisia N. Clarke, and Douglas B. Evans
Introduction 1048
Incidence and Etiology 1048
Classification, Histopathology, and Molecular Genetics 1048
Diagnosis and Management of Pancreatic Neuroendocrine
Tumors 1051
Functional Tumors 1056
Additional Clinical Considerations 1059
Small Nonfunctioning Sporadic Pancreatic Neuroendocrine
Tumors 1060
58. Carcinoid Tumors and the
Carcinoid Syndrome. 1064
Deshka Foster and Jeffrey A. Norton
Incidence and Etiology 1064
Anatomy and Pathology 1064
General Principles of Diagnosis and Staging 1064
General Management Principles 1065
Diagnosis, Staging, and Management by Primary Tumor
Site 1066
Diagnosis and Management of Carcinoid Syndrome 1068
Medical Management of NETS 1069
Management of GI NET Liver Metastases 1070
Conclusions 1071
59. Multiple Endocrine Neoplasia . 1073
Deshka Foster and Jeffrey A. Norton
Introduction 1073
Multiple Endocrine Neoplasia Type 1 1073
Multiple Endocrine Neoplasia Types 2 and 3 and Familial
Medullary Thyroid Cancer 1076
Multiple Endocrine Neoplasia Type 4 1078
SECTION 8. SARCOMAS AND SOFT TISSUE
60. Soft Tissue Sarcoma . 1080
Samuel Singer, William D. Tap, David G. Kirsch,
Narasimhan P. Agaram, Sandra P. D’Angelo, and Aimee M. Crago
Introduction 1080
Incidence and Etiology 1080
Anatomic and Age Distribution and Pathology 1081
Clinical and Pathologic Features of Specific Soft Tissue Tumor
Types 1084
Diagnosis and Staging 1102
Management by Presentation Status, Extent of Disease, and
Anatomic Location 1106
Future Directions 1126
61. Sarcomas of Bone. 1141
Richard J. O’Donnell, Steven G. DuBois, Daphne A. Haas-Kogan,
Steven E. Braunstein, and Meera Hameed
Introduction 1141
Incidence and Etiology 1141
Anatomy and Pathology 1142
Molecular Biology: Diagnostics and Biomarkers 1143
Screening 1151
Diagnosis 1152
Staging 1154
Management by Diagnosis and Stage 1154
Continuing Care: Surveillance and Palliation 1168
SECTION 9. CANCERS OF THE SKIN
62. Cancer of the Skin. 1177
Sherry H. Yu, Melissa Rasar Young, David J. Leffell, and
Sean R. Christensen
General 1177
Basal Cell Carcinoma 1181
Squamous Cell Carcinoma and Actinic Keratosis 1185
Merkel Cell Carcinoma 1193
Dermatofibrosarcoma Protuberans 1195
Angiosarcoma 1196
Microcystic Adnexal Carcinoma 1197
Sebaceous Carcinoma 1198
Extramammary Paget Disease 1198
Atypical Fibroxanthoma and Pleomorphic Dermal
Sarcoma 1199
63. Cutaneous Melanoma. 1205
Antoni Ribas, Charlotte E. Ariyan, and Christopher A. Barker
Introduction 1205
Classification of Melanoma Subtypes 1205
xxvi Contents
Molecular Biology of Melanoma 1208
Epidemiology 1212
Changes in Incidence 1213
Sex and Age Distribution 1213
Melanoma in Children, Infants, and Neonates 1213
Anatomic Distribution 1214
Etiology and Risk Factors 1214
Prevention and Screening 1215
Diagnosis of Primary Melanoma 1217
General Considerations in Clinical Management of a Newly
Diagnosed Cutaneous Melanoma (Stages I and II) 1220
Clinical Trials to Define Margins of Excision for Primary
Cutaneous Melanomas 1221
Surgical Staging of Regional Nodes 1222
Selection of Patients for Sentinel Node Biopsy 1223
Management of Clinically Localized Melanoma 1223
Thick Melanomas (T4a, T4b, >4 mm Thick) 1225
Special Considerations in Management of Primary
Melanomas 1225
Radiotherapy for a Primary Melanoma 1227
Clinical Follow-Up for Intermediate-Thickness and Thick
Melanomas (Stage IB to IIC) 1228
Regionally Metastatic Melanoma (Stage III): Lymph Node
Metastasis, Satellite Lesions, and In-Transit Metastases 1228
Adjuvant Lymph Node Basin Radiotherapy 1233
Neoadjvuant Therapy in Melanoma 1234
Adjuvant Systemic Therapy for Stage III-IV after Surgical
Resection 1236
Management of Distant Metastases of Melanoma
(Stage IV) 1238
Radiation Therapy for Oligometastatic Melanoma 1254
SECTION 10. CNS
64. Neoplasms of the Central
Nervous System . 1263
Mark W. Youngblood, Stephen T. Magill, Roger Stupp,
and Christina Tsien
Epidemiology of Brain Tumors 1263
Classification and Pathology 1265
Clinical Considerations by Anatomic Location 1266
Neurodiagnostic Tests and Imaging 1267
Surgery 1270
Radiation Therapy 1271
Systemic Treatments (Cytotoxic Chemotherapy, Targeted Agents,
and Immunotherapy) 1273
Specific Central Nervous System Neoplasms 1276
Gliomatosis Cerebri 1294
Optic, Chiasmal, and Hypothalamic Gliomas 1294
Brain Stem Gliomas 1296
Cerebellar Astrocytomas 1297
Gangliogliomas 1298
Ependymoma 1299
Meningiomas 1300
Primitive Neuroectodermal or Embryonal Central Nervous
System Neoplasms 1303
Pineal Region Tumors and Germ Cell Tumors 1308
Pituitary Adenomas 1309
Craniopharyngiomas 1311
Vestibular Schwannomas 1312
Glomus Jugulare Tumors 1314
Hemangioblastomas 1314
Chordomas and Chondrosarcomas 1315
Choroid Plexus Tumors 1318
Spinal Axis Tumors 1319
SECTION 11. CANCERS IN ADOLESCENTS
AND YOUNG ADULTS
65. Adolescents and Young Adults
with Cancer . 1333
Archie Bleyer, Andrea Ferrari, Michael Osborn, Lynn Ries,
and Ronald D. Barr
Introduction 1333
Epidemiology 1333
Etiology and Biology 1334
Signs, Symptoms, and Delays in Diagnosis 1335
Prevention and Screening 1340
Diagnosis 1340
Management 1340
Progress 1345
Future Challenges 1349
SECTION 12. LYMPHOMAS IN ADULTS
66. Hodgkin Lymphoma . 1353
Anas Younes, Ahmet Dogan, Peter W.M. Johnson, Joachim
Yahalom, Ann S. LaCasce, and Stephen Ansell
Introduction 1353
Etiology 1353
Pathology of Hodgkin Lymphoma 1353
Staging 1356
Early-Stage Hodgkin Lymphoma 1357
Advanced-Stage Hodgkin Lymphoma 1363
Special Circumstances 1366
67. Non-Hodgkin Lymphoma. 1371
Caron A. Jacobson, Andrea Ng, Jon C. Aster,
and Arnold S. Freedman
Introduction 1371
Incidence and Etiology 1371
Lymphoma Classification: the Principles of the World
Health Organization Classification of Lymphoid
Neoplasms 1375
Differential Diagnosis and Sites of Disease at Presentation 1375
Initial Management 1377
Staging and Prognostic Systems 1377
Specific Disease Entities 1379
Mature T-Cell and Natural Killer Cell Neoplasms 1393
68. Cutaneous Lymphomas . 1408
Francine M. Foss, Tarsheen Sethi, Michael Girardi,
and Lynn D. Wilson
Introduction 1408
Mycosis Fungoides and the Sézary Syndrome 1408
Epidemiology and Etiology 1408
Pathobiology 1409
Diagnosis and Staging 1410
The Sézary Syndrome 1410
Staging and Prognosis of Mycosis Fungoides and the Sézary
Syndrome 1412
Clinical Evaluation of Patients with Cutaneous Lymphoma 1412
Principles of Therapy of Mycosis Fungoides and the Sézary
Syndrome 1413
Skin-Directed Therapy 1413
Systemic Therapy for Mycosis Fungoides and the Sézary
Syndrome 1416
Other Cutaneous Lymphomas 1418
Contents xxvii
69. Primary Central Nervous
System Lymphoma. 1424
Teresa Calimeri, Andrés José María Ferreri, and Tracy Batchelor
Definition and Epidemiology 1424
Histopathology and Molecular Profile 1424
Diagnosis and Evaluation 1424
Prognostic Models 1426
Steroids and Surgery 1427
Treatment of Newly Diagnosed Primary Central Nervous System
Lymphoma 1427
Management of Refractory/Relapsed Primary Central Nervous
System Lymphoma 1429
Primary Vitreoretinal Lymphoma 1429
Monitoring and Follow-Up 1434
Neurotoxicity 1434
SECTION 13. LEUKEMIAS AND PLASMA
CELL TUMORS
70. Management of Acute Leukemias. 1437
Partow Kebriaei, Farhad Ravandi, Marcos de Lima,
and Richard Champlin
Introduction 1437
Acute Myeloid Leukemia 1437
Acute Lymphoblastic Leukemia 1446
71. Chronic Myeloid Leukemia. 1457
Carlo Gambacorti-Passerini and Philipp D. le Coutre
Introduction 1457
Epidemiology and Pathogenesis 1457
Diagnosis 1458
Differential Diagnosis, Staging, and Prognostic Factors 1458
Prognostic Factors 1459
Therapy 1459
Assessment of Response to Tyrosine Kinase Inhibitors 1462
Therapy of the Chronic Phase Chronic Myeloid Leukemia 1463
Treatment of Advanced Disease 1465
Future Directions 1466
72. Chronic Lymphocytic Leukemias. 1471
William G. Wierda and Susan M. O’Brien
Introduction 1471
Immunophenotype 1471
Molecular Biology 1471
Immune Abnormalities 1473
Diagnosis 1473
Clinical Manifestations 1473
Laboratory Findings 1473
Staging 1474
Indications for Treatment and Response Criteria 1475
Treatments for Chronic Lymphocytic Leukemia 1476
Management Considerations and Recommendations 1482
Prolymphocytic Leukemia 1484
Large Granular Lymphocyte Leukemia 1484
Hairy Cell Leukemia 1485
73. Myelodysplastic Syndromes . 1489
Rory M. Shallis, Mina L. Xu, Amer M. Zeidan,
and Stephanie Halene
Introduction 1489
Historical Perspective 1489
Epidemiology 1489
Pathogenesis 1489
Etiology 1492
Clinical Presentation 1493
Diagnosis 1493
Subtypes of Myelodysplastic Syndromes and Classification 1494
Risk Stratification and Survival 1495
Management 1496
Future Perspective 1499
Conclusion 1501
74. Plasma Cell Neoplasms. 1509
S. Vincent Rajkumar and Shaji Kumar
Introduction 1509
Multiple Myeloma 1509
Pathogenesis 1511
Cytogenetic Classification 1513
Clinical Features 1514
Diagnostic Tests 1514
Differential Diagnosis 1516
Staging and Risk Stratification 1517
Prognosis 1517
Treatment 1517
Supportive Care 1530
MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANCE (MGUS) 1531
Introduction 1531
Incidence and Prevalence 1531
Clinical Features 1531
Differential Diagnosis 1532
Prognosis 1532
Risk Stratification 1532
Management 1532
SMOLDERING MULTIPLE MYELOMA (SMM) 1532
Introduction 1532
Prevalence 1532
Clinical Features 1532
Differential Diagnosis 1534
Prognosis 1534
Risk Stratification 1535
Management 1535
Systemic AL (Immunoglobulin Light Chain) Amyloidosis 1536
Diagnosis 1536
Prognosis 1536
Treatment 1536
Solitary Plasmacytoma 1538
Diagnosis and Prognosis 1538
Treatment 1539
Poems Syndrome 1539
SECTION 14. OTHER CANCERS
75. Cancer of Unknown Primary. 1546
Sarah Yentz, Francis P. Worden, Erin F. Cobain, and Laurence Baker
Introduction 1546
Pathology Evaluation 1546
Additional Diagnostic Tests in Cancer of Unknown Primary 1548
Use of Next-Generation Sequencing 1548
Clinical Features and Evaluation 1549
Treatment 1549
Prognostic Factors 1552
76. Benign and Malignant Mesothelioma. 1554
Harvey I. Pass, Michele Carbone, Anne Tsao, and Kenneth Rosenzweig
Epidemiology 1554
Diagnosis and Evaluation 1558
Prognostication of MPM to Guide Clinical Management 1564
Treatment 1566
xxviii Contents
77. Peritoneal Metastases and Peritoneal
Mesothelioma . 1583
Paul H. Sugarbaker, Diane Goéré, Olivier Glehen,
Alvaro Arjona-Sanchez, and Marcello Deraco
Introduction 1583
Natural History of Peritoneal Metastases 1583
Treatment Options Based on Natural History and Pharmacologic
Studies 1584
Selection of Treatment Using Quantitative Prognostic
Indicators 1585
Treatment of Appendiceal Malignancy with Peritoneal
Metastases 1589
Curative Treatment and Prevention of Colorectal Peritoneal
Metastases 1589
Prevention and Treatment of Gastric Cancer Peritoneal
Metastases 1590
Treatment of Ovarian Cancer Peritoneal Metastases 1591
Management of Peritoneal Mesothelioma 1592
78. Intraocular Melanoma. 1596
Paul T. Finger, Anna C. Pavlick, and Wolfgang A.G. Sauerwein
Introduction 1596
Incidence and Etiology 1596
Anatomy and Pathology 1596
Ophthalmic Diagnosis 1597
Universal Uveal Melanoma Staging 1599
Management of Primary Uveal Melanoma 1600
Overview: Treatment of Choroidal Melanoma 1600
Treatment for Special Cases 1600
Diagnosis of Metastasis 1601
Biomarkers: Prognostic and Predictive Factors 1605
Summary 1605
SECTION 15. ONCOLOGIC EMERGENCIES
79. Superior Vena Cava Syndrome. 1608
Andreas Rimner and Joachim Yahalom
Introduction 1608
Anatomy and Pathophysiology 1608
Clinical Presentation and Etiology 1608
Diagnostic Workup 1610
Disease-Specific Management and Outcomes 1610
Small-Cell Lung Cancer 1610
Non–Small-Cell Lung Cancer 1610
Non-Hodgkin Lymphoma 1610
Nonmalignant Causes 1611
Catheter-Induced Obstruction 1611
Treatment 1611
Areas of Uncertainty 1612
Recommendations 1612
80. Increased Intracranial Pressure . 1614
Philipp Karschnia and Joachim M. Baehring
Introduction 1614
Pathophysiologic Considerations 1614
Epidemiology and Pathogenesis 1615
Clinical Presentation 1615
Diagnosis 1617
Treatment 1618
81. Spinal Cord Compression. 1621
Michael J. Strong, Joseph R. Evans, Nicholas J. Szerlip,
and William C. Jackson
Incidence and Etiology 1621
Anatomy and Pathophysiology 1621
Clinical Presentation 1621
Differential Diagnosis 1622
Diagnosis 1622
Grading 1622
Management by Stage 1623
82. Metabolic Emergencies. 1628
Hari A. Deshpande, Aarti Bhatia, and Stacey Stein
Introduction 1628
Tumor Lysis Syndrome and Hyperuricemia 1628
Hyponatremia 1629
Hypercalcemia 1630
Lactic Acidosis 1631
Hyperammonemia 1631
SECTION 16. TREATMENT OF METASTATIC
CANCER
83. Metastatic Cancer to the Brain. 1634
John H. Suh, Rupesh Kotecha, Manmeet S. Ahluwalia,
and Michael A. Vogelbaum
Introduction 1634
Epidemiology 1634
Clinical Presentation 1634
Imaging and Diagnosis 1634
Prognosis 1634
Symptom Management 1635
Treatment Options 1636
Leptomeningeal Metastases 1641
Follow-Up and Imaging 1642
84. Metastatic Cancer to the Lungs . 1647
Tanvi Subramanian and Jessica S. Donington
Introduction 1647
Presentation and Diagnosis of Pulmonary Metastases 1647
Surgical Metastasectomy 1648
Ablative Therapies 1651
Treatment Concerns and Outcomes for Individual
Histologies 1652
Conclusion 1655
85. Metastatic Cancer to the Liver. 1659
Clifford S. Cho, Sam Lubner, and Dawn Owen
Introduction 1659
Hepatic Colorectal Adenocarcinoma Metastases 1662
Hepatic Neuroendocrine Carcinoma Metastases 1667
Noncolorectal Non-Neuroendocrine Hepatic Metastases 1668
86. Metastatic Cancer to the Bone. 1672
Edward Chow, Joel A. Finkelstein, Quynh-Nhu Nguyen,
Arjun Sahgal, and Robert E. Coleman
Introduction 1672
Presentation 1672
Pathophysiology 1672
Diagnostic Evaluation 1672
Optimum Use of Bone-Targeted Agents in Metastatic
Bone Disease 1673
New Targeted Therapies in the Treatment of Metastatic
Bone Disease 1674
External-Beam Radiation Therapy 1674
Systemic Radionuclides 1676
Radiotherapy for Complicated Bone Metastases: Localized
External Beam 1677
Contents xxix
87. Malignant Pleural and Pericardial
Effusions. 1681
Robert Taylor Ripley
Malignant Pleural Effusions 1681
Treatment Algorithm 1684
Malignant Pericardial Effusions 1685
Conclusion 1687
88. Malignant Ascites . 1689
Mohamed Abdelgadir Adam and Ajay V. Maker
Incidence and Etiology 1689
Fluid Regulation and Pathophysiology 1689
Diagnosis 1689
Management 1690
89. Paraneoplastic Syndromes. 1698
Daniel Morgensztern, Siddhartha Devarakonda, Saiama N. Waqar,
and Ramaswamy Govindan
Introduction 1698
Paraneoplastic Neurologic Syndromes 1698
Paraneoplastic Endocrinology Syndromes 1700
Paraneoplastic Hematologic Syndromes 1703
Paraneoplastic Dermatologic Manifestations 1703
Paraneoplastic Rheumatologic Manifestations 1704
SECTION 17. MANAGEMENT OF ADVERSE
EFFECTS OF TREATMENT
90. Neutropenia and Thrombocytopenia. 1707
Michael Jaglal and Bilal D. Shah
Introduction 1707
91. Nausea and Vomiting. 1717
Elizabeth M. Blanchard and Paul J. Hesketh
Introduction 1717
Nausea and Vomiting Syndromes 1717
Pathophysiology of Treatment-Induced Nausea and
Vomiting 1717
Defining the Risk of Nausea and Vomiting 1718
Antiemetic Agents 1720
Lower Therapeutic Index 1722
Antiemetic Treatment by Clinical Setting 1722
Special Chemotherapy-Induced Nausea and Vomiting
Problems 1723
Radiotherapy-Induced Nausea and Vomiting 1725
92. Diarrhea and Constipation . 1728
Nathan I. Cherny and Batsheva Ziff-Werman
Introduction 1728
Diarrhea 1728
Neutropenic Colitis 1729
Ischemic Colitis (Non-Neutropenic Enterocolitis) 1729
Targeted Therapy–Associated Diarrhea 1730
Immunotherapy-Associated Diarrhea 1730
Radiotherapy-Induced Diarrhea 1730
Other Causes of Treatment-Related Diarrhea 1730
Assessment 1730
General Principles in the Management of Diarrhea 1731
Antidiarrheal Medications 1731
Specific Management Guidelines 1731
Radiation Therapy–Induced Diarrhea 1732
Immunotherapy-Induced Diarrhea and Colitis 1732
Management of Neutropenic Enterocolitis 1732
Diarrhea Prophylaxis 1733
Constipation 1733
Conclusion 1735
93. Oral Complications. 1738
Jane M. Fall-Dickson, Isabella F. Calastri, and Ann M. Berger
Introduction 1738
Oral Mucositis 1738
Radiation Therapy–Related Complications 1739
Pathogenesis of Chemotherapy- and Radiation Therapy-Induced
Oral Mucositis 1739
Chronic Graft-Versus-Host Disease Oral Manifestations 1740
Sequelae of Oral Complications 1740
Strategies for Prevention and Treatment of Oral
Complications 1741
Treatment Strategies 1741
Radioprotectors 1743
Biologic Response Modifiers 1744
Treatment for Oral Chronic Graft-Versus-Host Disease 1747
Symptom Management 1747
94. Cardiac Toxicity . 1753
Erel Joffe and Joachim Yahalom
Introduction 1753
Cardiomyopathy and Congestive Heart Failure 1754
Pretreatment Evaluation 1754
Surveillance Before, During, and after Treatment 1754
Cardioprotective Pharmacotherapy 1755
Stress Cardiomyopathy (Takotsubo Cardiomyopathy) 1755
Ischemic Heart Disease 1755
Agents Associated with Metabolic Abnormalities 1756
Clonal Hematopoiesis of Indeterminate Potential and
Accelerated Atherosclerosis 1756
Management of Ischemic Cardiac Events During
Chemotherapy 1756
Arrythmia and Long QTC Syndrome 1756
Immunotherapies, Myocarditis, Pericarditis, and Cytokine
Release 1757
Radiation-Associated Cardiovascular Disease 1757
Management and Long-Term Surveillance 1759
95. Gonadal Dysfunction. 1761
Marja Brolinson, Karrie Anne Brondell Walker,
and Alan H. DeCherney
Introduction 1761
Effects of Cytotoxic Agents on Adult Men 1761
Effects of Cytotoxic Agents on Adult Women 1763
Effects of Cytotoxic Agents on Children 1767
Gonadal Dysfunction after Cranial Irradiation 1767
Preservation of Fertility, Hormone Levels, and Sexual
Function 1767
Genetic Concerns 1770
Acknowledgments 1771
96. Fatigue . 1774
Sandra A. Mitchell and Ann M. Berger
Introduction 1774
Definition, Risk Factors, and Mechanisms of Cancer-Related
Fatigue 1774
Screening and Evaluation of the Patient with Cancer-Related
Fatigue 1775
Interventions for Cancer-Related Fatigue 1776
Pharmacologic Interventions 1776
Nonpharmacologic Interventions 1777
Complementary and Integrative Therapies 1778
Summary 1778
xxx Contents
97. Neurocognitive Effects. 1784
Michelle M. Kim, Nicolette M. Gabel, Kyle R. Noll,
Annette Compter, Sanne B. Schagen, and Jeffrey S. Wefel
Introduction 1784
Assessment and Clinical Significance of Neurocognitive
Function Impairment 1784
Incidence of Cancer-Related Cognitive Dysfunction 1784
Incidence and Mechanisms of Local Cancer Therapy-Related
Cognitive Dysfunction 1785
Incidence and Mechanisms of Systemic Cancer Therapy-Related
Cognitive Dysfunction 1786
Strategies to Mitigate Neurocognitive Effects of Cancer
Therapy 1787
Conclusion 1789
98. Management of Cancer Pain . 1791
Lauren Chiec and Judith A. Paice
Introduction 1791
Assessment 1791
Management 1793
Special Populations 1804
Conclusion 1806
Acknowledgment 1806
99. Nutrition Support . 1811
David A. August, Matthew A. Beier, and Catherine Hambleton Davis
Background 1811
Causes of Malnutrition in Cancer Patients 1811
Cancer Cachexia Syndrome (CCS) 1812
Nutrition Screening and Assessment 1813
Pharmacotherapy of Cancer-Associated Weight Loss and
Malnutrition 1814
Nutrition Support of Cancer Patients 1814
100. Sexual Problems. 1819
Lydia L. Chevalier and Sharon L. Bober
Introduction 1819
Cancer in Men 1819
Cancers that Affect Men and Women 1820
Cancer in Women 1821
Adolescent and Young Adult Cancer Survivors 1824
Relevant Sociocultural Considerations 1824
Disruption of Intimacy and Relational Considerations 1825
Communication About Sexual Problems 1825
101. Psychiatric Distress and Resilience. 1829
Sheila Lahijani, David Spiegel, and Michelle B. Riba
Introduction 1829
Common Psychiatric Conditions 1829
Screening for Psychological Problems 1830
Coping 1830
Treatment Interventions 1830
Psychoactive and Psychotropic Medications 1832
Conclusion 1833
102. How We Talk to Patients and How We Talk
to Ourselves. 1835
Lawrence Leichman, James L. Speyer, Mary Lynn Nierodzik,
and Franco M. Muggia
Introduction 1835
Organizing Thoughts for Discussion and Treatment 1835
The Potential for Cure: Hope and Caution 1836
Stage IV, Recurrence, and “The Plan” 1837
The Safety Net Hospital: Cultural and Social Challenges 1838
How We Talk to Ourselves and Our Colleagues 1839
Conclusion 1839
Acknowledgment 1839
103. Specialized Care of the Terminally Ill. 1840
Robert S. Krouse and Arif H. Kamal
Introduction 1840
Early Specialist Palliative Care 1840
Communication 1840
Specific Problems in the Setting of Advanced Cancer 1840
Impending Death 1843
Conclusion 1844
P A R T I V
Societal Issues
104. Cancer Survivorship . 1848
Sharon M. Castellino, Larissa Nekhlyudov, Matthew J. Ehrhardt,
Brooke O. Cherven, Patrick M. Reagan, Jennifer J. Griggs,
Louis S. Constine, and Susan K. Parsons
Introduction 1848
Definition of Survivorship and Scope of the Problem 1848
Goals of Survivorship Health Care 1850
Communication and Care Coordination 1852
Delivery of Follow-Up Care and Best Practice Models 1852
Educational Considerations 1853
Enhancing Research 1853
Financial Toxicity: Employment and Financial Hardship 1854
Conclusion 1854
105. Minority Health and Cancer
Health Disparities. 1857
Otis W. Brawley and Lorraine T. Dean
Introduction 1857
Minority Health Research 1857
The Causes of Cancer 1859
Disparities in Specific Cancers 1859
Quantifying Cancer Disparities in the United States 1861
106. Virtual Care and Telehealth in Oncology. 1864
Jeffrey B. Smerage and Andrew L. Rosenberg
Introduction 1864
Definitions; Telemedicine, Telehealth, and Virtual Care 1864
Telehealth Methods 1864
Types of Telehealth 1865
Clinical Impact in Oncology 1865
Frameworks to Consider How Telehealth Fits Into Care 1866
Telehealth Best Practices 1868
Regulatory Compliance, Legal and Billing 1869
Licensing, Reimbursement, and Liability 1869
Summary 1870
107. Complementary, Alternative,
and Integrative Therapies in Cancer Care. 1872
Ting Bao and Jun J. Mao
Introduction 1872
Lifestyle Modifications 1872
Mind-Body Interventions 1874
Dietary Supplements and Natural Products 1877
Conclusion 1877
Index. I-1