Holland-Frei Cancer Medicine

Cover......Page 1
Title Page......Page 5
Copyright......Page 6
Contents......Page 7
List of contributors......Page 13
Preface......Page 29
Acknowledgments......Page 31
Part 1 Introduction......Page 33
Chapter 1 Cardinal manifestations of cancer......Page 35
The future......Page 37
Acquired functional capabilities embody biological hallmarks of cancer......Page 39
Aberrations that enable acquisition of the necessary functional capabilities......Page 43
The histopathological complexity of cancer, manifested in tumor microenvironments (TMEs)......Page 45
Therapeutic targeting (and cotargeting) of cancer hallmarks......Page 46
References......Page 48
Part 2 Tumor Biology......Page 49
Overview: gene structure......Page 51
General techniques......Page 53
Gene expression: mRNA transcript analysis......Page 64
Epigenetic regulation......Page 69
Gene expression: protein analysis......Page 70
Functional screens for the identification of therapeutic targets in cancer......Page 74
Mouse models of human cancer......Page 75
Key references......Page 77
Discovery and identification of oncogenes......Page 79
Mechanisms of oncogene activation......Page 86
Oncogenes in the initiation and progression of neoplasia......Page 92
Oncogenes as target of new drugs......Page 93
Key references......Page 97
Genetic basis for tumor development......Page 99
Retinoblastoma: a paradigm for tumor suppressor gene function......Page 100
Key references......Page 114
Mechanisms involved in epigenetic regulation of gene expression......Page 117
Altered DNA methylation and chromatin in cancer or the "cancer epigenome"......Page 118
Clinical implications of altered DNA methylation in cancer......Page 120
Key references......Page 122
Introduction......Page 125
The history and methods of cancer genomics......Page 126
Cancer genome landscapes......Page 130
Cancer evolution......Page 136
Cancer genomics and evolution in clinical practice: A case study in melanoma......Page 140
Glossary......Page 144
Key references......Page 145
Genetic consequences of genomic rearrangements......Page 147
Methods that complement karyotype analysis......Page 148
Specific clonal disorders......Page 149
Key references......Page 162
Biogenesis and production of microRNAs......Page 163
MicroRNA deregulation in cancer......Page 164
MicroRNAs as noninvasive biomarkers in cancer......Page 165
Therapeutic targeting and miRNA......Page 166
References......Page 167
Growth factor receptors with Tyr kinase activity......Page 169
Signaling pathways of Tyr kinase receptors......Page 171
Other signaling pathways aberrantly deregulated in cancer......Page 173
Growth factor signaling and cancer therapy......Page 174
Key references......Page 177
Molecular mechanisms underlying differentiation blockage in cancer......Page 179
Potential cancer cell differentiation-inducing agents......Page 182
APL as a successful model of cancer differentiation therapy......Page 185
Perspectives......Page 188
Key references......Page 190
Cancer stem cell hypothesis......Page 191
Signal transduction pathways in cancer stem cells and their therapeutic targeting......Page 193
Clinical significance of cancer stem cells and future perspectives......Page 195
Key references......Page 197
Pathways for cell death......Page 199
Cell death resistance mechanisms used by cancers......Page 203
Signal transduction pathway alterations in cancers-impact on cell death machinery......Page 205
Cancer drug discovery by targeting the cell death machinery......Page 207
Key references......Page 209
Telomerase: a universal target for cancer therapy......Page 211
There are no telomere/telomerase-targeted drugs approved by the Food and Drug Administration (FDA)......Page 213
6-Thio-dG is a small molecule that is a telomerase-based telomere uncapping target that may overcome some of the problems with gene therapy......Page 216
Key references......Page 218
From yeast to mammals-same means to different ends......Page 219
The traveling electrons......Page 221
Warburg effect-how to play safe while looking sloppy......Page 222
The cavalry arrives!-glutamine and anabolic metabolism......Page 224
The nucleus smells what's cooking......Page 225
From petty thieves to ringleaders-how cancer cells corrupt their neighbors......Page 226
Cancer metabolism comes into the clinic......Page 227
Key references......Page 228
Introduction......Page 231
References......Page 236
Rationale for targeting tumor vasculature......Page 239
Historic background......Page 240
Biology of tumor angiogenesis......Page 241
Regulators of angiogenesis......Page 242
Therapeutic approaches to targeting tumor vasculature......Page 249
Clinical advances in the use of antiangiogenic therapy......Page 251
Lessons from clinical studies of antiangiogenic therapy and future directions......Page 258
Key references......Page 261
Part 3 Quantitative Oncology......Page 263
Chapter 18 Cancer bioinformatics......Page 265
The analog (microarray) to digital (sequencing) transition......Page 266
Bioinformatic analysis, visualization, and interpretation......Page 269
Hypothesis-generating and hypothesis-driven research......Page 270
Analysis and biointerpretation in major molecular profiling projects......Page 272
Statistical methods and associated pitfalls......Page 273
References......Page 278
Intrinsic systems biology and genomics in cancer......Page 279
Tumor microenvironment......Page 283
Conclusion......Page 285
Key references......Page 286
Chapter 20 Statistical innovations in cancer research......Page 287
Bayesian approach......Page 288
Analysis issues......Page 292
Principles of statistical design: decision analysis and factorial experiments......Page 295
Adaptive designs of clinical trials......Page 296
Key references......Page 302
Phase II trials of molecularly targeted agents with companion diagnostics......Page 303
Phase IIa basket and umbrella discovery trials......Page 304
Phase III designs with a single binary biomarker......Page 305
References......Page 308
An oncology digital health information technology system......Page 309
The mobile computing revolution......Page 313
References......Page 314
Part 4 Carcinogenesis......Page 317
Multistage carcinogenesis......Page 319
Epigenetics and chemical carcinogenesis......Page 322
miRNA's in chemical carcinogenesis......Page 323
Gene-environment interactions and inter-individual variation......Page 325
Carcinogen metabolism......Page 326
DNA damage and repair......Page 328
Racial, gender, and socioeconomic disparities in chemical carcinogenesis......Page 329
Chronic inflammation and cancer......Page 331
Oncogenes and tumor suppressor genes......Page 332
Precision medicine, molecular epidemiology, and prevention......Page 333
Key references......Page 337
Breast cancer......Page 339
Endometrial cancer......Page 344
Ovarian cancer......Page 346
Prostate cancer......Page 347
Genetic determinants......Page 348
Key references......Page 350
Principal cellular and tissue effects of radiation......Page 353
Chromosomal aberrations......Page 354
General characteristics of radiation carcinogenesis......Page 355
Human epidemiologic studies......Page 356
Key references......Page 357
Epidemiology of skin cancer......Page 359
Genetic factors in skin carcinogenesis......Page 360
Diseases of DNA repair......Page 361
Carcinogenesis......Page 362
Key references......Page 363
Inflammatory cells, the microenvironment, and cancer......Page 365
Pro- and anti-inflammatory cytokines in cancer......Page 366
Inflammation and tumorigenesis......Page 368
Inflammation-dependent cancers-examples and treatment......Page 369
Key references......Page 370
Structure......Page 373
Mechanisms of oncogenesis......Page 374
Oncogene capture......Page 375
Insertional mutagenesis......Page 376
Growth stimulation and two-step oncogenesis......Page 377
Transactivation......Page 378
Endogenous retroviruses......Page 380
Retroviral vectors and gene therapy......Page 382
Key references......Page 383
EBV: an oncogenic human herpesvirus......Page 385
KSHV and malignancies......Page 388
Key references......Page 390
Definitions, HPV-target cells, and mechanisms of infection and transformation......Page 393
HPV and human genital neoplasia......Page 395
Key references......Page 397
Hepatitis and hepatoma......Page 399
Key references......Page 403
Epidemiologic aspects......Page 405
Metabolic observations during schistosomiasis......Page 406
Experimental data for BBC......Page 407
East Asian distomiasis......Page 408
Malaria......Page 409
Key references......Page 410
Part 5 Epidemiology, Prevention and Detection......Page 413
Definitions, data sources, and methods......Page 415
Global cancer diversity......Page 416
Global cancer transitions......Page 426
References......Page 428
Cancer health disparities......Page 431
Emerging cancer risk factors......Page 433
Genetic susceptibility......Page 434
Emerging methods and technologies......Page 435
Perspective and future direction......Page 436
Key references......Page 437
Tobacco use......Page 439
Energy balance: diet, physical activity, and body weight......Page 440
Key references......Page 444
Chapter 36 Diet and nutrition in the etiology and prevention of cancer......Page 447
Methodologic issues in diet, nutrition, and cancer studies......Page 449
Public health guidelines for cancer prevention......Page 450
Summary of research efforts focusing on specific cancers......Page 452
Current research......Page 458
Survivorship: diet and nutritional guidance during and following cancer treatment......Page 461
Prevention of cancer recurrences and long-term complication of therapy......Page 462
Key references......Page 463
Chemoprevention trials......Page 465
Conclusions......Page 468
Key references......Page 469
Evaluation of early detection programs......Page 471
Breast cancer screening......Page 473
Colorectal cancer......Page 477
Cervical cancer......Page 479
Prostate cancer......Page 481
Lung cancer......Page 483
Ovarian cancer......Page 484
Melanoma and nonmelanoma skin cancer......Page 485
Key references......Page 486
Part 6 Clinical Disciplines......Page 489
From anatomic and clinical pathology to molecular and predictive integrated diagnostics......Page 491
Molecular pathology......Page 492
Bladder cancer as a model of molecular pathology classification......Page 493
Systems pathology and predictive oncology......Page 494
From treating symptomatology to treating disease causation......Page 496
References......Page 498
Introduction......Page 501
Current molecular biomarkers for predicting outcomes and therapy responsiveness......Page 504
Molecular biomarkers for monitoring of cancer......Page 506
Novel molecular biomarkers and platforms for their detection......Page 507
Recommendations......Page 510
Key references......Page 511
Further reading......Page 513
Hepatic vascular interventions......Page 515
Considerations in hepatic metastases......Page 518
Genitourinary interventions......Page 519
Palliative therapy......Page 520
Key references......Page 521
Chapter 43 Principles of surgical oncology......Page 523
The history of surgical oncology......Page 524
Surgical oncology in the modern era......Page 526
Components of surgical management in the care of the cancer patient......Page 528
The future of surgical oncology......Page 533
References......Page 534
General principles of radiotherapy in cancer treatment......Page 535
Biologic impact of radiation therapy......Page 536
Physical and clinical aspects of modern radiotherapy......Page 539
Key references......Page 541
Principles......Page 543
Cancer therapeutics is evolving......Page 546
References......Page 551
Communication......Page 553
Advance care planning......Page 554
Symptom management......Page 555
Key references......Page 558
Hospice......Page 560
Key references......Page 561
Clinical management......Page 563
Burnout in oncology......Page 567
References......Page 568
Spinal cord dysfunction......Page 569
Cancer of the limbs......Page 571
References......Page 572
Utilization......Page 575
The evidence......Page 576
Integrative oncology in clinical practice......Page 578
Key references......Page 579
Disciplines within health services research......Page 581
Types of secondary data sources relevant to HSR in oncology......Page 582
Statistical analyses in health services research......Page 583
Different outcomes methods......Page 585
Quality of care......Page 587
Outcomes and endpoints......Page 588
Comparative effectiveness research......Page 590
Part 7 Individualized Treatment......Page 591
Role of biomarkers and companion diagnostics in personalized medicine......Page 593
Personalized immunotherapeutics......Page 598
Key references......Page 600
Part 8 Chemotherapy......Page 603
Evolution of the discovery process......Page 605
Special aspects developing protein-engineered compounds......Page 609
Preparation of agents for clinical trials......Page 610
Early clinical trials......Page 611
Are Phase I clinical trials therapeutic?......Page 616
Issues regarding Phase I trials in general......Page 617
Key references......Page 618
Molecular classification versus cancer stem cell concept......Page 621
Gompertzian growth......Page 622
Growth fraction, death fraction, tumor size, and therapeutic response......Page 623
The kinetics of chemotherapy response......Page 624
The etiology of Gompertzian growth......Page 628
The interrelationship of tumor self-seeding and tumor microenvironment......Page 629
References......Page 630
Dose......Page 633
Factors influencing the dose effect......Page 634
Schedule of drug administration......Page 638
Combination chemotherapy......Page 639
Molecular biology/targeted therapy......Page 642
Key references......Page 643
General attributes of the drug......Page 645
General clinical pharmacology......Page 646
Intrinsic factors......Page 653
General biopharmaceutics......Page 654
Key references......Page 655
Mechanisms of action of MTX......Page 657
Pharmacokinetics of MTX......Page 658
Clinical application......Page 660
Current uses for MTX in the treatment of neoplastic disease......Page 661
Adverse effects......Page 662
Resistance to antifolates......Page 664
Strategies to overcome resistance to MTX using new (or older) antifols......Page 665
Key references......Page 666
Uracil antimetabolites......Page 669
Cytosine antimetabolites......Page 671
Guanine antimetabolites......Page 675
Adenosine antimetabolites......Page 677
References......Page 680
General mechanisms of cytotoxicity......Page 681
Alkylating agents......Page 682
Platinum antitumor compounds......Page 692
Key references......Page 695
Mechanisms of action......Page 697
Topoisomerase I inhibitors......Page 700
Top2 inhibitors......Page 704
Pharmacogenomics......Page 707
References......Page 709
Microtubules as strategic targets against cancer......Page 711
Microtubules and mitosis......Page 712
Vinca alkaloids: Introduction and indications......Page 713
Mechanism of action......Page 715
Mechanisms of resistance......Page 716
Pharmacology......Page 717
Toxicity......Page 719
Administration, dose, and schedule......Page 721
Clinical indications......Page 722
Mechanisms of action......Page 724
Mechanisms of resistance......Page 725
Clinical pharmacology......Page 727
Drug interactions......Page 729
Toxicity......Page 730
Administration, dose, and schedule......Page 733
Ixabepilone and the epothilones......Page 735
Clinical pharmacology......Page 736
Toxicity......Page 737
Administration, dose, and schedule......Page 738
Mechanism of action......Page 739
Administration, dose, and schedule......Page 740
Targeting mitotic motor proteins and kinases......Page 741
Antibody-drug conjugates carrying antimicrotubule drug payloads......Page 742
Key references......Page 744
Biology of progestin production and action......Page 745
Biology of estrogen production and action......Page 747
Selective estrogen receptor modulators and antiestrogens......Page 749
Aromatase inhibitors......Page 754
Resistance to endocrine therapy......Page 761
Conclusion......Page 763
Key references......Page 764
General mechanisms of resistance to single agents......Page 765
General mechanisms of resistance to multiple agents......Page 766
Potential clinical application of strategies to avert or overcome drug resistance......Page 769
References......Page 770
Part 9 Biological and Gene Therapy......Page 773
Interleukins......Page 775
Interferons......Page 783
Hematopoiesis and the role of growth factors......Page 785
Key references......Page 788
Serotherapy for leukemia and lymphoma with unmodified monoclonal antibodies......Page 789
Serotherapy for solid tumors with unmodified monoclonal antibodies......Page 792
Immune checkpoint inhibitors......Page 798
Barriers to treatment with unmodified monoclonal antibodies......Page 799
Serotherapy with monoclonal antibody drug conjugates (ADCs)......Page 800
Radioimmunotherapy of cancer......Page 801
Therapy with targeted toxins......Page 804
Key references......Page 806
Targets for vaccine therapy......Page 809
Types of vaccines......Page 810
Non-specific immune stimulants......Page 812
Vaccine clinical trials......Page 813
Combination therapies......Page 817
Mechanisms involved in vaccine activity......Page 821
Immune monitoring......Page 822
Key references......Page 823
Introduction......Page 825
Conclusion......Page 831
Key references......Page 832
Immunoediting......Page 833
Early failures-lessons learnt......Page 834
Noncell-autonomous suppression......Page 835
Adoptive cell therapy and the development of personalized immunotherapies......Page 837
Generation of cellular therapy products......Page 838
Promoting DC function......Page 839
Stimulatory antibodies to 4-1BB (CD137), OX40 (CD134), and GITR-accentuating the positive?......Page 840
Stimulation through checkpoint blockade of CTLA-4 (CD152), PD-1 (CD279), PD-L1 (CD274)-eliminating the negative......Page 842
Targeting Treg suppressive capacity......Page 844
Combinatorial immunotherapeutics......Page 845
Key references......Page 846
Delivery of genetic material to target cells......Page 849
Targets of gene therapy......Page 851
Key references......Page 854
Clinical stage cancer nanotechnologies......Page 857
Key references......Page 861
Hematopoietic transplantation as treatment for malignancies......Page 863
Donor selection......Page 864
Selection of autologous or allogeneic transplantation......Page 865
Pretransplant therapy......Page 866
Complications of hematopoietic transplantation......Page 867
Indications for hematopoietic transplantation......Page 869
Key references......Page 872
Part 10 Special Populations......Page 875
Introduction and epidemiology......Page 877
Renal tumors......Page 882
Neuroblastoma......Page 884
Pediatric bone tumors......Page 885
Central nervous system tumors......Page 888
Less-frequently encountered tumors......Page 890
Late effects and quality of survivorship......Page 892
Key references......Page 894
Diagnosis and staging......Page 897
Systemic therapy......Page 898
Specific cancers......Page 900
Acute and chronic leukemia......Page 903
Key references......Page 904
The biology of cancer and aging......Page 907
The frail older patient......Page 908
Comorbid medical conditions......Page 909
Comprehensive geriatric assessment......Page 911
Cancer screening in the elderly......Page 912
Treatment tolerance of the older patient......Page 913
Key references......Page 914
Defining health disparities......Page 915
Population categorization......Page 916
Relationships among population categories......Page 917
Genetic expression-race, ancestry, ethnicity, and culture......Page 918
Pharmacogenomics......Page 919
References......Page 920
Epidemiology......Page 923
Kaposi sarcoma (KS)......Page 925
Non-Hodgkin lymphoma (NHL)......Page 931
Squamous cell neoplasia......Page 938
Key references......Page 940
Magnitude of the problem......Page 941
Providing survivorship care......Page 944
Conclusion......Page 946
Key references......Page 947
Part 11 Disease Sites......Page 949
Epidemiology......Page 951
Low-grade gliomas and oligodendrogliomas......Page 958
Ependymoma......Page 959
Primary central nervous system lymphoma......Page 960
Meningioma......Page 961
Pathophysiology of the metastatic process......Page 962
Key references......Page 965
Pediatric ophthalmic oncology: ocular diseases......Page 967
Adult ophthalmic oncology: ocular diseases......Page 973
Adult ophthalmic oncology: orbital diseases......Page 977
References......Page 978
Chapter 79 Neoplasms of the endocrine glands: pituitary neoplasms......Page 981
Prolactin-secreting pituitary adenomas......Page 983
Growth hormone-secreting pituitary adenomas......Page 984
Adrenocorticotrophic hormone-secreting adenomas......Page 986
Gonadotropin-secreting and nonsecretory pituitary adenomas......Page 987
Conclusion......Page 988
Key references......Page 989
Pathology......Page 991
Screening......Page 992
Prognostic factors......Page 993
Multidisciplinary care......Page 994
Key references......Page 996
Management of ACC......Page 999
Conclusion......Page 1000
References......Page 1001
Epidemiology......Page 1003
The diffuse endocrine system......Page 1004
Gastrointestinal neuroendocrine tumors (GI-NETs)......Page 1005
Pancreatic net (PNET) (islet-cell tumors)......Page 1006
Therapy for GEP-NET......Page 1008
MEN syndromes......Page 1009
MEN-2 syndromes......Page 1010
Key references......Page 1011
Descriptive epidemiology......Page 1013
Anatomy......Page 1016
Diagnosis and staging......Page 1018
General principles of treatment......Page 1019
Overview of natural history and treatment by site......Page 1020
Radiation therapy......Page 1035
Systemic therapy......Page 1038
Key references......Page 1041
Etiology and epidemiology......Page 1043
Pathology of lung cancer......Page 1044
Clinical manifestations......Page 1048
Diagnostic and staging techniques......Page 1050
Therapy for NSCLC......Page 1054
Therapy for SCLC......Page 1062
Conclusions and future prospects......Page 1066
Key references......Page 1067
Incidence and epidemiology......Page 1069
Diagnosing and staging the patient with possible mesothelioma......Page 1071
Treatment......Page 1073
Key references......Page 1081
Incidence and epidemiology......Page 1083
Pathology of thymic epithelial neoplasms......Page 1084
Staging systems for thymomas......Page 1086
TNM staging project-ITMIG/IASLC......Page 1088
Clinical features of thymomas......Page 1089
Therapy......Page 1090
Key references......Page 1092
Diagnostic evaluation......Page 1095
Cardiac tumors......Page 1096
Key references......Page 1098
Malignant GCT......Page 1101
Treatment of seminoma......Page 1102
Treatment of nonseminomatous GCT......Page 1103
Key references......Page 1104
Etiology......Page 1107
Epidemiology......Page 1108
Pretreatment assessment......Page 1109
Presentation......Page 1110
Therapy......Page 1113
Key references......Page 1121
Risk factors......Page 1123
Pathogenesis and natural history......Page 1124
Screening......Page 1125
Multidisciplinary care......Page 1126
Key references......Page 1132
Hepatocellular carcinoma......Page 1135
Intrahepatic cholangiocarcinoma......Page 1143
Hepatic angiosarcoma......Page 1144
Key references......Page 1145
Gallbladder cancer......Page 1147
Bile duct cancer......Page 1152
Hilar bile duct cholangiocarcinoma......Page 1156
Key references......Page 1159
Etiologic factors......Page 1161
Pathology......Page 1164
Diagnostic evaluation......Page 1167
Treatment of localized, potentially resectable disease......Page 1169
Adjuvant (postoperative) therapy......Page 1172
Preoperative (neoadjuvant) therapy......Page 1173
Locally advanced pancreatic cancer......Page 1174
The role of systemic therapy in pancreatic cancer......Page 1176
Approach to the patient with metastatic disease......Page 1178
Future directions......Page 1179
Key references......Page 1180
Tumors of the small intestine......Page 1183
Tumors of the appendix......Page 1189
Carcinoma of the colon and rectum......Page 1191
Key references......Page 1207
Etiology......Page 1209
Diagnosis......Page 1210
Prognostic factors......Page 1211
Treatment for primary disease......Page 1212
Management of inguinal nodes......Page 1216
Key references......Page 1217
Pathology......Page 1219
Treatment of localized RCC......Page 1220
Metastatic disease......Page 1221
Conclusion......Page 1224
Key references......Page 1225
Pathobiology and molecular determinants......Page 1227
Investigation and staging......Page 1229
Management of non-muscle-invasive bladder cancer......Page 1230
Management of invasive bladder cancer......Page 1231
Uncommon histologic variants......Page 1233
Upper tract tumors......Page 1234
Key references......Page 1235
Biology of prostate cancer......Page 1237
Early detection of prostate cancer......Page 1242
Staging of prostate cancer......Page 1243
Outcomes of treatment for early disease......Page 1249
Prostate cancer chemoprevention: Large trials......Page 1252
Locally advanced disease......Page 1254
Metastatic prostate cancer......Page 1257
Histologic variants......Page 1264
Clinical presentations......Page 1265
Key references......Page 1266
Metastasis......Page 1269
Surgical treatment......Page 1270
Radiotherapy......Page 1271
Carcinoma of the urethra......Page 1272
References......Page 1273
Epidemiology......Page 1275
Pathology......Page 1276
Clinical presentation......Page 1279
Therapy......Page 1281
Therapy for disseminated disease......Page 1286
Treatment of good-risk disseminated germ cell tumors......Page 1287
Treatment of patients with "poor-risk" disseminated disease......Page 1288
Postchemotherapy surgery......Page 1289
High-dose chemotherapy as initial salvage therapy......Page 1292
Special situations......Page 1293
Long-term toxicity of chemotherapy......Page 1294
Long-term toxicity of radiation therapy......Page 1296
Extragonadal germ cell tumors (EGCTs)......Page 1297
Unrecognized germ cell tumor syndrome......Page 1298
Key references......Page 1299
Cancer of the vulva......Page 1301
Sentinel inguinal lymph node biopsy......Page 1303
Treatment......Page 1304
Invasive carcinomas of the vagina......Page 1309
Clear cell adenocarcinoma of the vagina......Page 1310
Rare vaginal tumors in young females......Page 1311
Key references......Page 1312
Epidemiology......Page 1313
Histologic classification of epithelial tumors......Page 1315
Diagnosis and treatment of precancerous lesions......Page 1317
Diagnosis and treatment of invasive lesions patterns of spread......Page 1321
Radiation therapy......Page 1326
Current practice by disease stage......Page 1329
Key references......Page 1336
Risk factors......Page 1337
Pathology......Page 1338
Prognostic factors......Page 1341
Treatment of primary disease......Page 1342
Treatment of recurrent disease......Page 1344
Key references......Page 1347
Incidence, etiology, and epidemiology......Page 1349
Genetic predisposition......Page 1350
Molecular, cellular, and clinical biology......Page 1352
Diagnosis......Page 1356
Screening......Page 1357
Staging......Page 1358
Prognosis......Page 1359
Treatment of advanced stage epithelial cancer......Page 1360
Treatment of recurrent epithelial cancer......Page 1366
Key references......Page 1369
Germ cell malignancies......Page 1371
Dysgerminomas......Page 1372
Immature teratoma......Page 1375
Endodermal sinus tumor......Page 1376
Mixed germ cell tumor......Page 1377
Granulosa-stromal cell tumors......Page 1379
Sarcomas......Page 1381
Metastatic tumors......Page 1382
Key references......Page 1383
Histopathologic classification of GTN......Page 1385
Staging and risk assessment......Page 1386
Management of high-risk GTN, stages II and III......Page 1387
Management of stage IV GTN......Page 1388
Management of PSTT and ETT......Page 1389
Key references......Page 1390
Molecular and genetic alterations......Page 1393
Imaging studies......Page 1394
Morcellation......Page 1395
Radiation oncology......Page 1396
Combination chemotherapy......Page 1397
Nonuterine gynecologic sarcomas......Page 1398
Key references......Page 1399
Epidemiology......Page 1401
Regulation of breast cancer growth......Page 1406
Pathology......Page 1408
Prognostic factors......Page 1411
Diagnosis and screening......Page 1413
Risk and prevention......Page 1417
Treatment of early-stage breast cancer......Page 1420
Treatment for advanced breast cancer......Page 1451
Symptom management and survivorship......Page 1470
Key references......Page 1471
Dermatologic principles in melanoma......Page 1473
Clinical presentation......Page 1474
Less-common subtypes......Page 1475
Genetics and molecular pathology......Page 1476
Surgical management of melanoma......Page 1477
The role of adjuvant therapy for stage II and III disease......Page 1480
Adjuvant radiation to the resected nodal basin......Page 1481
Uveal melanoma and rare melanomas of the eye......Page 1482
Biology and therapy of advanced melanoma......Page 1483
Tumor-infiltrating lymphocyte (TIL) therapy in melanoma......Page 1489
Key references......Page 1490
Tumors arising from the epidermis......Page 1493
Tumors arising from dermis......Page 1501
Benign cutaneous tumors associated with cancer syndromes......Page 1502
Metastatic tumors to the skin......Page 1503
Key references......Page 1504
Evaluation......Page 1507
Biopsy......Page 1509
Surgical margins......Page 1510
Reconstructive alternatives......Page 1511
Radiotherapy for bone tumors......Page 1512
Specific benign bone tumors......Page 1513
Primary bone sarcomas......Page 1519
Metastatic disease to bone......Page 1526
Congenital syndromes......Page 1527
Multiple osteochondromatosis......Page 1528
Key references......Page 1529
Etiology......Page 1531
Clinical presentation, classification, and diagnosis......Page 1532
Staging and prognostic factors......Page 1536
Treatment of localized primary disease of the extremities......Page 1538
Treatment of metastatic disease......Page 1549
Management of local recurrence......Page 1554
Gastrointestinal stromal tumors......Page 1555
Retroperitoneal sarcomas......Page 1556
Additional issues in STS management......Page 1557
Key references......Page 1558
Chapter 113 The myelodysplastic syndrome......Page 1561
Pathogenesis and etiology......Page 1577
Prognosis......Page 1579
Morphologic classification and clinical and laboratory correlates......Page 1580
AML with recurrent genetic abnormalities......Page 1582
AML not otherwise specified......Page 1584
Presenting signs and symptoms......Page 1587
Induction therapy: general principles......Page 1588
Therapy of relapsed and refractory AML......Page 1593
Therapy of acute promyelocytic leukemia (APL)......Page 1594
Other supportive care and therapeutic approaches......Page 1596
Small-molecule inhibitors and other novel approaches......Page 1597
Central nervous system leukemia......Page 1598
Mast cell leukemia and other mast cell neoplasms......Page 1599
Key references......Page 1600
Pathology......Page 1603
Prognostic classification......Page 1604
Pathogenesis......Page 1605
Diagnosis......Page 1606
Treatment......Page 1607
Treatment options after failure of prior TKI......Page 1608
Treatment recommendations in CML in 2015......Page 1609
Key references......Page 1610
Clinical presentation......Page 1613
Diagnosis of ALL......Page 1614
The therapy of ALL......Page 1617
Disease subtypes......Page 1621
Novel therapies......Page 1622
Key references......Page 1624
Immunobiology and immunophenotype of CLL cells......Page 1627
Clinical presentation......Page 1628
Natural history and terminal events......Page 1629
Criteria predictive of disease course in the low- and intermediate-risk groups......Page 1630
Treatment......Page 1631
Unmet needs and future directions......Page 1634
Key references......Page 1635
Epidemiology and etiology......Page 1637
Pathology......Page 1638
Immunophenotype and biology......Page 1639
Principles of treatment in classical Hodgkin lymphoma......Page 1641
Post-treatment surveillance......Page 1644
Key references......Page 1645
Pathology, immunobiology, and natural history of NHL......Page 1647
Gray zone lymphoma......Page 1652
Differential diagnosis and sites of disease at presentation......Page 1653
Disease parameters that influence prognosis and assessment of disease response......Page 1654
Therapeutic approaches according to WHO classification......Page 1655
Key references......Page 1660
Prognostic factors and biomarkers......Page 1661
Key references......Page 1665
Epidemiology......Page 1667
Biology......Page 1668
Prognostic factors......Page 1674
Complications......Page 1675
Treatment......Page 1677
Relapsed disease......Page 1683
Future directions......Page 1686
Waldenström macroglobulinemia......Page 1687
Amyloidosis......Page 1688
Key references......Page 1689
Essential thrombocythemia......Page 1691
Primary myelofibrosis......Page 1694
Polycythemia vera......Page 1697
Key references......Page 1700
Part 12 Management of Cancer Complications......Page 1703
Pathologic evaluation......Page 1705
Clinical evaluation......Page 1708
Treatment......Page 1710
Key references......Page 1714
Etiology and mechanisms......Page 1717
Treatment......Page 1720
Key references......Page 1722
Pathophysiology of nausea and vomiting......Page 1725
Classes of antiemetics......Page 1726
Recommendations for prevention and treatment of chemotherapy-induced emesis......Page 1729
Key references......Page 1730
Metastases......Page 1733
Cranial and peripheral nerve metastases......Page 1739
Nonmetastatic complications of cancer therapy......Page 1741
Cerebrovascular complications of cancer......Page 1745
References......Page 1746
Targeted cancer therapeutics......Page 1749
Immunomodulators......Page 1752
Extravasation reactions......Page 1753
Radiation-associated reactions......Page 1754
Acral reactions......Page 1756
Cutaneous eruption of lymphocyte recovery......Page 1757
Key references......Page 1758
Solitary lesions of bone......Page 1759
Options for treatment of skeletal lesions......Page 1760
Intramedullary nailing......Page 1761
Arthroplasty......Page 1762
Megaprostheses......Page 1763
Spine lesions......Page 1764
References......Page 1767
Abnormalities of red cells and red cell support......Page 1769
Leukopenia and white cell support......Page 1770
Single- and multiple-donor platelets......Page 1771
Other therapeutic modalities......Page 1772
Transfusion-related infectious diseases......Page 1773
Human T-cell lymphotrophic virus type 1......Page 1774
Key references......Page 1775
Physiology of normal hemostasis......Page 1777
Bleeding disorders......Page 1778
Thrombotic complications......Page 1781
Heparin-induced thrombocytopenia (HIT)......Page 1783
Disseminated intravascular coagulation (DIC)......Page 1784
Drugs for treatment of bleeding and thrombotic disorders......Page 1785
Key references......Page 1786
Urinary tract obstruction......Page 1787
Cystitis and nephritis......Page 1788
Diagnosis, treatment, and prevention of nephrotoxicity of cancer therapeutic agents......Page 1789
Key references......Page 1794
Evaluation of the cardiovascular system in the cancer patient......Page 1795
Metastatic involvement of cardiac structures......Page 1796
Cardiac effects of mediator release, high output states, and infiltrative disorders in cancer patients......Page 1799
Cardiac complications of cancer treatment......Page 1802
References......Page 1812
Malignant airway obstruction......Page 1813
Malignant pleural effusions......Page 1814
Postsurgical respiratory insufficiency......Page 1819
Chemotherapy-induced lung injury......Page 1820
Pulmonary complications of thoracic radiation: Radiation pneumonitis and fibrosis......Page 1827
Pulmonary complications of hematopoietic stem cell transplantation......Page 1828
Pneumonia......Page 1830
Pulmonary hypertension in the cancer patient......Page 1831
Sleep disorders in cancer patients......Page 1832
Acute respiratory failure......Page 1833
Key references......Page 1836
Esophageal disorders......Page 1839
Diarrhea......Page 1842
Colitis......Page 1844
Intestinal manifestations of graft-versus-host disease......Page 1846
Hepatic complications of cancer treatment......Page 1847
Other GI complications of cancer therapy......Page 1850
Key references......Page 1851
Pretreatment assessment......Page 1853
Oral complications of radiotherapy......Page 1854
Oral complications of chemotherapy......Page 1858
Oral complications associated with HSCT......Page 1862
Key references......Page 1863
Assessment of gonadal function after gonadotoxic therapy......Page 1865
Effects of cytotoxic chemotherapy on gonadal function......Page 1866
Effects of targeted therapies on gonadal function......Page 1869
Protective measures......Page 1870
Outcomes of pregnancy......Page 1871
Key references......Page 1872
Incidence and epidemiology-local and worldwide......Page 1875
Screening......Page 1876
Unmet needs, future directions, and conclusions......Page 1877
Key references......Page 1878
Endocrine complications......Page 1881
Endocrine paraneoplastic syndromes ("ectopic" hormone production)......Page 1890
Key references......Page 1895
Infections primarily associated with impaired cellular and humoral immunity......Page 1897
Spectrum of infection......Page 1898
Fungal infections......Page 1901
Viral infections......Page 1903
Special situations......Page 1904
Therapy of infections in patients with neutropenia......Page 1905
Duration of therapy......Page 1906
Antifungal and antiviral prophylaxis......Page 1907
Key references......Page 1908
Circulatory oncologic emergencies......Page 1911
Respiratory oncologic emergencies......Page 1920
Neurologic oncologic emergencies......Page 1923
Other oncologic emergencies......Page 1925
Key references......Page 1929
Part 13 The Future of Oncology......Page 1931
The early stages......Page 1933
The book of life-four levels of biological information......Page 1934
Systems medicine: a tipping point......Page 1935
P4 medicine: a revolution in healthcare......Page 1936
100,000 Person Wellness Project......Page 1937
Hundred Pioneer pilot study results......Page 1938
Systems medicine and cancer: a postscript......Page 1939
References......Page 1940
Index......Page 1943
EULA......Page 2004