Holland-Frei Cancer Medicine (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 recur