سرطان: اصول و شیوه‌های آنکولوژی، ویرایش دهم

Cancer Principles & Practice of Oncology......Page 1 CONTRIBUTORS......Page 8 PREFACE......Page 26 Acknowledgments ......Page 28 CONTENTS......Page 30 PART I Principles of Oncology......Page 48 IDENTIFICATION OF CANCER GENES......Page 49 SOMATIC ALTERATION CLASSES DETECTED BY CANCER GENOME ANALY SIS......Page 57 PATHWAY-ORIENTED MODELS OF CANCER GENOME ANALY SIS......Page 58 NETWORKS OF CANCER GENOME PROJECTS......Page 60 THE GENOMIC LANDSCAPE OF CANCERS......Page 62 THE CANCER GENOME AND THE NEW TAXONOMY OF TUMORS......Page 63 CANCER GENOMICS AND DRUG RESISTANCE......Page 66 Acknowledgments......Page 67 HALLMARK CAPABILITIES, IN ESSENCE......Page 71 TWO UBIQUITOUS CHARACTERISTICS FACILITATE THE ACQUISITION OF HALLMARK CAPABILITIES......Page 80 THE CONSTITUENT CELL TYPES OF THE TUMOR MICROENVIRONMENT......Page 82 THERAPEUTIC TARGETING OF THE HALLMARKS OF CANCER......Page 88 CONCLUSION AND A VISION FOR THE FUTURE......Page 89 Acknowledgment......Page 90 Applications of Molecular Diagnostics in Oncology......Page 92 The Clinical Molecular Diagnostics Laboratory: Rules and Regulations......Page 95 Molecular Diagnostics Testing Process......Page 96 Technologies......Page 97 PART II Etiology and Epidemiology of Cancer......Page 108 EPIDEMIOLOGY OF TOBACCO AND CANCER......Page 109 CARCINOGENS IN TOBACCO PRODUCTS AND PROCESSES OF CANCER DEVELOPMENT......Page 111 PRINCIPLES OF TUMOR VIROLOGY......Page 116 PAPILLOMAVIRUSES......Page 118 POLYOMAVIRUSES......Page 120 EPSTEIN-BARR VIRUS......Page 121 KAPOSI’s SARCOMA HERPESVIRUS......Page 122 ANIMAL AND HUMAN RETRO VIRUSES......Page 124 HEPATITIS VIRUSES......Page 126 CONCLUSION......Page 128 ROLE OF INFLAMMATION IN TRANSFORMATION......Page 130 ROLE OF INFLAMMATION IN SURVIVAL......Page 131 ROLE OF INFLAMMATION IN ANGIOGENESIS......Page 132 EPIGENETIC CHANGES AND INFLAMMATION......Page 133 CONCLUSIONS......Page 134 THE NAT URE OF CHEMICAL CARCINOGENS: CHEMISTRY AND META BOLISM......Page 136 ANIMAL MODEL SYSTEMS AND CHEMICAL CARCINOGENESIS......Page 137 MOLECULAR EPIDEMIOLOGY, CHEMICAL CARCINOGENESIS, AND CANCER RISK IN HUMAN POPULATION S......Page 138 ARISTOLO CHIC ACID AND UROT HELIAL CANCERS AS A MODEL FOR IDENTIFYING HUMAN CARCINOGENS......Page 139 IONIZING RADIATION......Page 142 ULTRAVIOLET LIGHT......Page 145 RADIOFREQUENCY AND MICROWAVE RADIATION......Page 146 ASBESTOS......Page 147 NANOPARTICLES......Page 148 METHODOLOGIC CHALLENGES......Page 150 THE ROLE OF INDIVIDUAL FOOD AND NUTRIENTS IN CANCER ETIOLOGY ......Page 151 OTHER FOODS AND NUTRIENTS......Page 155 DIET AFTER A DIAGNOSIS OF CANCER......Page 157 LIMITATIONS......Page 158 RECOMMENDATIONS......Page 159 BREAST CANCER......Page 161 COLON AND RECTAL CANCER......Page 162 ENDOMETRIAL CANCER......Page 163 PROSTATE CANCER......Page 164 CONCLUSIONS......Page 165 ANALYTICAL STUDIES......Page 167 CANCER OUTCOMES RESEARCH......Page 170 MOLECULAR EPIDEMIOLOGY......Page 171 CANCER INCIDENCE AND MORTALITY......Page 175 PREDICTING FUTURE CANCER TRENDS......Page 180 PART III Cancer Therapeutics......Page 182 BIOLOGIC ASPECTS OF RADIATION ONCOLOGY......Page 183 FACTORS THAT AFFECT RADIATION RESPONSE......Page 188 DRUGS THAT AFFECT RADIATION SENSITIVITY......Page 190 RADIATION PHYSICS......Page 191 TREATMENT PLANNING......Page 195 OTHER TREATMENT MODALITIES......Page 196 CLINICAL APPLICATIONS OF RADIATION THERAPY......Page 198 TREATMENT INTENT......Page 199 ADVERSE EFFECTS......Page 200 PRINCIPLES OF COMBINING ANTICANCER AGENTS WITH RADIATION THERAPY......Page 202 HUMAN TUMOR ANTIGENS......Page 205 HUMAN CANCER IMMUNOTHERAPIES......Page 208 PHARMACOKINETIC CONCEPTS......Page 221 VARIABILITY IN PHARMACOKINETICS/ PHARMACODYNAMICS......Page 223 DOSE-ADAPTATION USING PHARMACOKINETIC/PHARMACODYNAMIC PRINCIPLES......Page 227 PHARMACOGENOMICS OF TUMOR RESPONSE......Page 230 PHARMACOGENOMICS OF CHEMOTHERAPY DRUG TOXICITY......Page 233 CONCLUSIONS AND FUTURE DIRECTIONS......Page 235 CLASSIFICATION......Page 236 CLINICAL PHARMACOKINETICS/ PHARMACODYNAMICS......Page 240 THERAPEUTIC USES......Page 241 TOXICITIES......Page 242 ALKYLATING AGENT–STEROID CONJUGATES......Page 243 RECENT DEVELOPMENTS......Page 244 PLATINUM COMPLEXES AFTER CISPLATIN......Page 246 CELLULAR RESPONSES TO PLATINUM-INDUCED DNA DAMAGE......Page 248 MECHANISMS OF RESISTANCE......Page 249 CLINICAL PHARMACO LOGY......Page 250 TOXICITY......Page 252 ANTIFOLATES......Page 255 5-FLUOROPYRIMIDINES......Page 257 CAPECITABINE......Page 259 CYTARABINE......Page 260 6-THIOPURINES......Page 261 CLADRIBINE......Page 262 CLOFARABINE......Page 263 TOPOISOMERASE INHIBITORS AS INTERFACIAL POISONS......Page 265 Topoisomerase I Inhibitors : Camptothecins and Beyond......Page 267 TOPOISOMERASE II INHIBITORS: INTERCALATORS AND NONINTERCALATORS......Page 270 FUTURE DIRECTIONS......Page 273 TAXANES......Page 275 VINCA ALKALOIDS......Page 279 MITOTIC MOTOR PROTEIN INHIBITORS......Page 281 MECHANISMS OF RESISTANCE TO MICROTUBULE INHIBITORS......Page 282 EARLY SUCCESSES: TAR GETING CANCERS WITH WELL-KNOWN KINASE MUTATI ONS (BCR-ABL, KIT, HER2)......Page 284 COMBINATIONS OF KINASE INHIBITORS TO INDUCT RESPONSE AND PREVENT RESISTANCE......Page 292 SPECULATI ONS ON THE FUTURE ROLE OF KINASE INHIBITORS IN CANCER MEDICINE......Page 293 EPIGENETIC ABNORMALITIES AND GENE EXPRESSION CHANGES IN CANCER......Page 295 HISTONE DEACETYLASE INHIBITORS......Page 299 EPIGENETIC THERAPY FOR HEMATOLOGIC MALIGNANCIES......Page 301 NEW APROACHES TO EPIGENETIC THERAPY......Page 303 PROTEASOME INHIBITORS......Page 305 PROTEASOME INHIBITORS IN CANCER......Page 306 BRCA1 AND BRCA2 MUTATIONS AND DNA REPAIR......Page 310 INITIAL CLINICAL RESULTS TESTING SYNTHETIC LETHALITY OF PARP INHIBITORS AND BRCA MUTATION......Page 311 MECHANISMS OF RESISTANCE TO PARP INHIBITORS......Page 312 PROSPECTS......Page 313 L-ASPARAGINASE......Page 314 PROCARBAZINE......Page 315 SIROLIMUS AND TEMSIROLIMUS......Page 316 THALIDOMIDE, LENALIDOMIDE, AND POMALIDOMIDE......Page 317 SELECTIVE ESTROGEN RECEPTOR MODULATORS......Page 325 AROMATASE INHIBITORS......Page 329 GONADOTROPIN-RELEASING HORMONE ANALOGS......Page 331 ANTIANDROGENS......Page 332 OTHER SEX STEROID THERAPIES......Page 333 OTHER HORMONAL THERAPIES......Page 335 UNDERSTANDING THE ANGIOGENIC PROCESS......Page 337 DRUG DEVELOPMENT OF ANGIOGENESIS INHIBITORS......Page 338 CLINICAL UTILITY OF APPROVED ANTIANGIOGENIC AGENTS IN CANCER THERAPY......Page 340 BIOMARKERS OF ANTIANGIOGENIC THERAPY......Page 344 RESISTANCE TO ANTIANGIOGENIC THERAPY......Page 345 MODIFIED ANTIBODY-BASED MOLECULES......Page 347 UNCONJUGATED ANTIBODIES......Page 349 IMMUNOCONJUGATES......Page 350 ANTIBODIES APPROVED FOR USE IN SOLID TUMORS......Page 351 ANTIBODIES USED IN HEMATOLOGIC MALIGNANCIES......Page 352 CONCLUSION......Page 353 ASSESSING RESPONSE......Page 355 ALTERNATE RESPONSE CRITERIA......Page 358 DETERMINING OUTCOME......Page 360 PART IV Cancer Prevention and Screening......Page 368 TOBACCO USE PREVALENCE AND THE EVOLUTION OF TOBACCO PRODUCTS......Page 369 THE CLINICAL EFFECTS OF SMOKING ON THE CANCER PATIENT......Page 370 ADDRESSING TOBACCO USE BY THE CANCER PATIENT......Page 373 FUTURE CONSIDERATIONS......Page 379 PATIENTS AT HIGH RISK FOR BREAST CANCER......Page 382 HEREDITARY DIFFUSE GASTRIC CANCER......Page 384 SURGICAL PROPHYLAXIS OF HEREDITARY OVARIAN AND ENDOMETRIAL CANCER......Page 386 HEREDITAR Y ENDOMETRIAL CANCER (LYNCH SYNDRO ME)......Page 387 MULTIPLE ENDOCRINE NEOPLASIA TYPE 2......Page 388 FAMILIAL ADENOMATOUS POLYPOSIS, MYH-ASSOCIATED POLUPOSIS, AND LYNCH SYNDRO ME......Page 391 PRECLINICAL DEVELOPMENT OF CANCER RISK–REDUCING AGENTS......Page 397 CLINICAL DEVELOPMENT OF CANCER RISK–REDUCING AGENTS......Page 399 MICRONUTRIENTS......Page 401 ANTI-INFLAMMATORY DRUGS......Page 407 EPIGENETIC TARGETING AGENTS (SELECTIVE ESTROGEN RECEPTOR MODULATORS, 5α-STEROID REDUCTASE INHIBITORS, POLYAMINE INHIBITORS)......Page 408 SIGNAL TRANSDUCTION MODIFIERS......Page 411 MULTIAGENT APPROACHES TO CANCER RISK REDUCTION......Page 413 ASSESSING SCREENING TESTS AND OUTCOMES......Page 417 PROBLEMS WITH RANDOMIZED TRIALS......Page 419 BREAST CANCER......Page 420 Colon Cancer Screening......Page 425 Other Cancers of the Gastrointestinal Tract......Page 426 GYNECOLOGIC CANCER......Page 427 LUNG CANCER SCREENING......Page 429 PROSTATE CANCER SCREENING......Page 430 SKIN CANCER SCREENING......Page 432 WHO IS A CANDIDATE FOR CANCER GENETIC COUNSELING?......Page 436 COMPONENTS OF THE CANCER GENETIC COUNSELING SESSION......Page 437 ISSUES IN CANCER GENETIC COUNSELING......Page 440 RECENT ADVANCES AND FUTURE DIRECTIONS......Page 442 PART V Practice of Oncology......Page 444 PHASE 1 CLINICAL TRIALS......Page 445 PHASE 2 CLINICAL TRIALS......Page 447 DESIGN OF PHASE 3 CLINICAL TRIALS......Page 451 FACTORIAL DESIGNS......Page 454 ANALYSIS OF PHASE 3 CLINICAL TRIALS......Page 456 META-ANALYSIS......Page 460 INTRODUCTION......Page 463 MOLECULAR MECHANISMS IN Head and Neck Squamous Cell Carcinoma......Page 465 CANCER STEM CELLS......Page 466 NATURAL HISTORY......Page 469 STAGING......Page 470 MANAGEMENT......Page 471 NECK......Page 472 CHEMOTHERAPY......Page 474 GENERAL PRINCIPLES OF COMBINING MODALITIES......Page 477 CHEMOTHERAPY AS PART OF CURATIVE TREATMENT......Page 478 FOLLOW-UP......Page 483 LIP......Page 484 FLOOR OF THE MOUTH......Page 485 ORAL TONGUE......Page 486 GINGIVA AND HARD PALATE (INCLUDING RETROMOLAR TRIGONE)......Page 488 PATTERNS OF SPREAD......Page 490 TREATMENT: BASE OF TONGUE......Page 491 TREATMENT: TONSILLAR AREA......Page 492 TREATMENT: SOFT PALATE......Page 493 PATTERNS OF SPREAD......Page 494 DIFFERENTIAL DIAGNOSIS AND STAGING......Page 495 TREATMENT: SUPRAGLOTTIC LARYNX CARCINOMA......Page 496 TREATMENT: SUPRAGLOTTIC LARYNX CANCER......Page 497 ANATOMY......Page 498 STAGING......Page 499 TREATMENT......Page 500 ANATOMY......Page 501 TREATMENT......Page 502 NASAL VESTIBULE, NASAL CAVITY, AND PARANASAL SINUSES......Page 504 PARAGANGLIOMAS......Page 509 MAJOR SALIVARY GLANDS......Page 510 MINOR SALIVARY GLANDS......Page 514 SUPPORT DURING TREATMENT AND REHABILITATION OF THE CHEMORADIATION PATIENT......Page 521 RESOURCES FOR REHABILITATION OF HEAD AND NECK CANCER PATIENTS......Page 527 MOLECULAR CHANGES IN PRENEOPLASIA......Page 529 PROTOONCOGENES, GROWTH FACTOR SIGNALING, AND GROWTH FACTOR– TARGETED THERAPIES......Page 531 THE TECHNOLOGY OF GENOMIC ANALYSES OF LUNG CANCER......Page 533 TUMOR SUPPRESSOR GENES AND GROWTH SUPPRESSION......Page 534 OTHER PUTATIVE TUMOR SUPPRESSORS......Page 535 OTHER BIOLOGIC ABNORMALITIES IN LUNG CANCER......Page 536 microRNAS IN LUNG CANCER DIAGNOSTICS AND THERAPY......Page 537 miRNA PROFILING IN LUNG CANCER......Page 538 INVASION, METASTASIS, AND ANGIOGENESIS......Page 539 MOLECULAR TOOLS IN THE LUNG CANCER CLINIC......Page 540 INCIDENCE AND ETIOLOGY......Page 542 ANATOMY AND PATHOLOGY......Page 545 PREVENTION AND SCREENING......Page 549 DIAGNOSIS......Page 551 STAGE EVALUATION......Page 552 MANAGE MENT BY STAGE......Page 555 SPECIAL CLINICAL SITUATION S......Page 573 PALLIATIVE CARE......Page 575 CONCLUSION......Page 577 SMALL CELL LUNG CANCER......Page 583 TY PICAL AND ATY PICAL CARCINOID TUMORS......Page 599 LARGE CELL NEUROENDOCRINE CARCINOMA......Page 602 THYMOMA......Page 607 THYMIC CARCINOMA......Page 608 THYMIC CARCINOID......Page 613 GERM CELL TUMORS......Page 614 MOLECULAR BIOLOGY OF ESOPHAGEAL CANCER......Page 617 MOLECULAR BIOLOGY OF GASTRIC CANCER......Page 619 ETIOLOGIC FACTORS AND PREDISPOSING CONDITIONS......Page 621 APPLIED ANATOMY AND HISTOLOGY......Page 624 DIAGNOSTIC STUDIES AND PRETREATMENT STAGING......Page 626 PATHOLOGIC STAGING......Page 628 TREATMENT......Page 629 STAGE-DIRECTED TREATMENT RECOMMENDATIONS......Page 655 ANATOMIC CONSIDERATIONS......Page 660 PATHOLOGY AND TUMOR BIOLOGY......Page 661 CLINICAL PRESENTATION AND PRETREATMENT EVALUATION......Page 662 PRETREATMENT STAGING......Page 663 STAGING, CLASSIFICATION, AND PROGNOSIS......Page 665 TREATMENT OF LOCALIZED DISEASE......Page 668 TECHNICAL TREATMENT-RELATED ISSUES......Page 679 TREATMENT OF ADVANCED DISEASE (STAGE IV)......Page 681 SURGERY IN TREATMENT OF META STATIC GASTRIC CANCER......Page 687 RADIATION FOR PALLIATION......Page 688 ETIOLOGY......Page 690 EPIDEMIOLOGY OF GASTRIC CANCER......Page 691 SCREENING AND MANAGEMENT OF CANCER RISK IN HDGC......Page 692 OTHER HEREDITARY CANCER SUSCEPTIBILITY SYNDROMES WITH INCREASED GASTRIC CANCER RISK......Page 693 CONCLUSIONS......Page 695 COMMON MOLECULAR CHANGES......Page 698 EPIDEMIOLOGY......Page 704 EXOCRINE PANCREATIC CANCERS......Page 705 ENDOCRINE PANCREATIC CANCERS......Page 709 STAGE I AND II: LOCALIZED PANCREATIC DUCTAL ADENOCARCINOMA......Page 710 STAGE III: LOCALLY ADVANCED DISEASE......Page 719 EMERGING ROLE OF STEREOTACTIC BODY RADIOTHERAPY......Page 722 STAGE IV: METASTATIC DISEASE......Page 723 FUTURE DIRECTIONS AND CHALLENGES......Page 727 CONCLUSION......Page 730 SELECTED GENES THAT MAY CAUSE PANCREATIC CANCER......Page 732 EMPIRIC RISK COUNSELING AND MANAGEMENT......Page 734 GENETIC ALTERATIONS IN LIVER CANCER......Page 737 MUTATIONAL LANDSCAPE OF GENETIC ALTERATIONS IN HCC: THE NEXT GENERATION......Page 738 THE MICROENVIRONMENT OF LIVER CANCER......Page 740 CLASSIFICATION AND PROGNOSTIC PREDICTION OF HEPATOCELLULAR CARCINOMA......Page 741 CONCLUSION AND PERSPECTIVE......Page 742 ETIOLOGIC FACTORS......Page 743 DIAGNOSIS......Page 745 TREATMENT OF HEPATOC ELLULAR CARCINOMA......Page 746 ADJUVANT AND NEOADJUVANT THERAPY......Page 749 TREATMENT OF OT HER PRIMARY LIVER TUMORS......Page 759 ANATOMY OF THE BILIARY TRACT......Page 762 CHOLANGIOCARCINOMA......Page 763 GALLBLADDER CANCER......Page 773 SMALL BOWEL CANCER......Page 781 ADENOCARCINOMA......Page 783 CARCINOID TUMORS......Page 786 SMALL BOWEL LYMPHOMA......Page 787 GASTROINTESTINAL STROMAL TUMORS......Page 788 OTHER MESENCHYMAL TUMORS......Page 789 METASTATIC CANCER TO THE SMALL BOWEL......Page 790 ANATOMY AND PATHOLOGY......Page 792 SCREENING......Page 794 DIAGNOSIS......Page 795 STAGING......Page 796 MANAGEMENT BY STAGE......Page 797 PALLIATIVE CARE......Page 801 MULTISTEP MODELS OF COLORECTAL TUMORIGENESIS......Page 804 INHERITED SYNDRO MES OF INCREASED CANCER RISK HIGHLIGHT EARLY EVENTS AND CRITICAL PAT HWAY S IN COLORECTAL TUMORIGENESIS......Page 805 ONCOGENE AND TUMOR SUPPRESSOR GENE MUTATION S IN COLORECTAL CANCER PROGRE SSION......Page 809 THE MUTATIONAL LANDSCAPE OF COLORECTAL CANCER......Page 812 SUMMARY......Page 813 EPIDEMIOLOGY......Page 815 ETIOLOGY: GENETIC AND ENVIRONMENTAL RISK FACTORS......Page 816 FAMILIAL COLORECTAL CANCER......Page 818 ANATOMY OF THE COLON......Page 820 DIAGNOSIS OF COLORECTAL CANCER......Page 821 SCREENING FOR COLORECTAL CANCER......Page 822 STAGING AND PROGNOSIS OF COLORECTAL CANCER......Page 823 APPROACHES TO SURGICAL RESECTION OF COLON CANCER......Page 829 SURGICAL MANAGEMENT OF COMPLICATIONS FROM PRIMARY COLON CANCER......Page 831 POLYPS AND STAGE I COLON CANCER......Page 832 STAGE II AND STAGE III COLON CANCER......Page 833 TREATMENT OF STAGE II PATIENTS......Page 835 TREATMENT OPTIONS FOR STAGE III PATIENTS......Page 837 FOLLOW-UP AFTER MANAGEMENT OF COLON CANCER WITH CURATIVE INTENT......Page 839 MANAGEMENT OF UNRESECTABLE METASTATIC DISEASE......Page 840 MOLECULAR PREDICTIVE MARKERS......Page 855 Adenomatous Polyposis......Page 860 HAMARTOMATOUS POLY POSIS......Page 863 CONCLUSIONS......Page 865 TUMOR SCREENING......Page 866 Acknowledgment......Page 868 ANATOMY......Page 870 STAGING......Page 871 SURGERY......Page 873 PREOPERATIVE RADIATION THERAPY......Page 879 WHICH PATIENTS SHOULD RECEIVE ADJUVANT THERAPY?......Page 881 CONCURRENT CHEMOTHERAPY......Page 883 MANAGEMENT OF UNRESECTABLE PRIMARY AND LOCALLY ADVANCED DISEASE (T4)......Page 884 RADIATION THERAPY TECHNIQUE......Page 885 EPIDEMIOLOGY AND ETIOLOGY......Page 889 PATHOLOGY......Page 890 PROGNOSTIC FACTORS......Page 892 TREATMENT OF LOCALIZED SQUAMOUS CELL CARCINOMA......Page 893 TREATMENT OF OTHER SITES AND PATHOLOGIES......Page 900 VON HIPPEL-LINDAU DISEASE......Page 904 BIRT-HOGG-DUBÉ SYNDROME......Page 906 HEREDITARY LEIOMYO MATOSIS AND RENAL CELL CARCINOMA......Page 907 CONCLUSION......Page 909 PATHOLOGY OF RENAL CELL CARCINOMA......Page 912 DIFFERENTIAL DIAGNOSIS AND STAGING......Page 913 HEREDITARY KIDNEY CANCER SYNDRO MES, GENETICS, AND MOLECULAR BIOLOGY......Page 914 TREATMENT OF LOCALIZED RENAL CELL CARCINOMA......Page 916 TREATMENT OF LOCALLY ADVANCED RENAL CELL CARCINOMA......Page 920 SURGICAL MANAGEMENT OF ADVANCED RENAL CELL CARCINOMA......Page 923 SYSTEMIC THERAPY FOR ADVANCED RENAL CELL CARCINOMA......Page 924 Acknowledgments......Page 929 KEY MOLECULAR ALTERATION S IN STAGE Ta UROTHELIAL CARCINOMA......Page 932 KEY MOLECULAR ALTERATION S IN INVASIVE UROTHELIAL CARCINOMA......Page 936 INFORMATION FROM EXOME SEQUENCING......Page 939 MULTI PLE TUMOR SUBGROUPS DEFINED BY MOLECULAR PROFILING......Page 940 ACKNOWLEDGEMENTS......Page 941 UROTHELIAL CANCERS......Page 943 CANCER OF THE BLADDER......Page 945 CANCERS OF THE RENAL PELVIS AND URETER......Page 957 GENETIC SUSCEPTIBILITY TO RENAL CELL CARCINO MA......Page 964 GENETIC TESTING AND COUNSELING......Page 967 SUMMARY......Page 969 ANDROGEN RECEPTOR BIOLOGY AND THERAPY......Page 970 ADDITIONAL PATHWAY S FREQUENTLY ALTERED DURING DISEASE PROGRE SSION......Page 972 E26 transformation specific (ETS) GENE FUSIONS AND THE MOLECULAR SUBTYPES OF PROSTATE CANCER......Page 974 EMERGING AREAS IN PROSTATE CANCER BIOLOGY AND THERAPY......Page 975 INCIDENCE AND ETIOLOGY......Page 979 ANATOMY AND PATHOLOGY......Page 981 SCREENING......Page 984 DIAGNOSIS, RISK ASSESSMENT, AND STATE ASSIGNMENT......Page 986 MANAGEMENT BY CLINICAL STATES......Page 991 PALLIATION......Page 1020 FUTURE DIRECTIONS......Page 1021 CANCER OF T HE MALE URETHRA......Page 1028 CARCINO MA OF THE FEMALE URETHRA......Page 1029 CANCER OF THE PENIS......Page 1030 HISTO LOGY......Page 1035 BIOLOGY......Page 1037 STAGING......Page 1039 MANAGEMENT OF CLINICAL STAGE I DISEASE......Page 1042 MANAGEMENT OF CLINICAL STAGE II (LOW TUMOR BURDEN)......Page 1044 MANAGEMENT OF STAGE II WITH HIGH TUMOR BURDEN AND STAGE III DISEASE......Page 1045 MANAGEMENT OF RECURRENT DISEASE......Page 1047 TREATMENT SEQUELAE......Page 1048 OT HER TESTICULAR TUMORS......Page 1049 OVARIAN CANCER......Page 1052 ENDOMETRIAL CANCER......Page 1056 CERVIX, VAGINAL, AND VULVAR CANCERS......Page 1057 CARCINOMA OF THE VAGINA......Page 1060 CARCINOMA OF THE VULVA......Page 1065 CARCINOMA OF THE CERVIX......Page 1071 ENODOMETRIAL CARCINOMA......Page 1095 UTERINE SARCOMAS......Page 1107 LYNC H SYNDRO ME (ALSO KNOWN AS HEREDITARY NONPOLYPOSIS COLORECTAL CANCER SYNDROME)......Page 1112 HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CARCINOMA......Page 1113 CONCLUSION......Page 1114 INDICATIONS FOR TREATMENT......Page 1116 PRETREATMENT EVALUATION......Page 1117 TREATMENT......Page 1118 PSYCHOSOCIAL ISSUES......Page 1120 EPITHELIAL OVARIAN CANCER......Page 1122 BORDERLINE TUMORS......Page 1139 GERM CELL TUMORS OF THE OVARY......Page 1140 SEX CORD–STROMAL TUMORS......Page 1142 PRIMARY PERITONEAL SEROUS CARCINOMA......Page 1143 FALLOPIAN TUBE CANCER......Page 1144 HEREDITARY BREAST AND OVARIAN CANCER SYNDROM (THE BRCA1 AND BRCA2 GENES)......Page 1147 LYNCH SYNDROME......Page 1149 NEWER GENES......Page 1150 CONCLUSION......Page 1151 HEREDITARY BREAST CANCER......Page 1154 SOMATIC CHANGES IN BREAST CANCER......Page 1157 TRANSCRIPTIONAL PROFILING OF BREAST CANCER......Page 1158 ESTROGEN RECEPTOR PATHWAY......Page 1160 SUMMARY......Page 1162 RISK FACTOR S FOR BREAST CANCER......Page 1164 MANAGEMENT OF THE HIGH-RISK PATIENT......Page 1167 LOBULAR CARCINOMA IN SITU......Page 1169 DUCTAL CARCINOMA IN SITU......Page 1170 STAGING......Page 1172 PATHOLOGY OF BREAST CANCER......Page 1174 LOCAL MANAGEMENT OF INVASIVE CANCER......Page 1175 MANAGEMENT OF THE AXILLA......Page 1183 POSTMASTECTO MY RADIATION THERAPY......Page 1184 PROGNOSTIC AND PREDICTIVE FACTORS IN BREAST CANCER......Page 1185 ADJUVANT SYSTEMIC THERAPY......Page 1187 FOLLO W-UP FOR BREAST CANCER SURVIVORS......Page 1191 SPECIAL THERAPEUTIC PROBLEMS......Page 1192 METASTATIC DISEASE......Page 1195 BRCA 1 AND BRCA 2......Page 1204 TP53......Page 1206 COWDEN SYNDRO ME (PHOSPHATE AND TENSIN HOMOLOG )......Page 1207 Moderateand Low-Penetrance Breast Cancer Genes......Page 1209 CONCLUSION......Page 1210 THE MULTIPLE ENDOCRINE NEOPLASIA SYNDRO MES......Page 1213 THYROID CARCINOMAS......Page 1218 FUTURE DIRECTIONS......Page 1220 THYROID NODULES......Page 1222 DIFFERENTIATED THYROID CANCER......Page 1224 TREATMENT OF DIFFERENTIATED THYROID CANCER......Page 1227 ANAPLASTIC THYROID CARCINOMA......Page 1230 MEDULLARY THYROID CANCER......Page 1231 THYROID LY MPHOMA......Page 1233 CHILDREN WITH THYROID CARCINOMA......Page 1234 ANATOMY AND PATHOLOGY......Page 1236 DIAGNOSIS......Page 1237 MANAGEMENT OF PARATHYROID CANCER......Page 1238 PROGNOSIS......Page 1239 OVERVIEW AND PATHOPHYSIOLOGY OF THE ADRENAL GLAND......Page 1242 INCIDENCE AND EPIDEMIOLOGY......Page 1243 DIAGNOSIS OF ADRENAL NEOPLASIA......Page 1244 IMPORTANT CONSIDERATIONS IN PERIOPERATIVE MANAGEMENT OF ADRENAL TUMORS......Page 1246 Management of Recurrent or Metastatic Malignant Pheochromocytoma......Page 1247 SURVEILLANCE AND ADJUVANT THERAPY FOR ADRENOCORTICAL CARCINOMA......Page 1248 MANAGEMENT OF METASTATIC OR UNRESECTABLE ADRENOCORTICAL CARCINOMA......Page 1249 Acknowledgments......Page 1250 CLASSIFICATION , HISTOPATHOLOGY , MOLECULAR GENETICS......Page 1252 DIAGNOSIS AND MANAGEMENT OF PANCREATIC NEUROENDOCRINE TUMORS......Page 1255 ADDITIONAL CLINICAL CONSIDERATIONS......Page 1262 SURGERY PITFALLS......Page 1263 GENERAL PRINCIPLES OF NEUROENDOCRINE TUMOR DIAGNOSIS, STAGING, AND MANAGEMENT......Page 1265 DIAGNOSIS, STAGING, AND MANAGEMENT BY PRIMARY TUMOR SITE......Page 1267 DIAGNOSIS AND MANAGEMENT OF CARCINOID SYNDROME......Page 1269 ANTITUMOR MANAGEMENT......Page 1270 MANAGEMENT OF LIVER METASTASES......Page 1271 CONCLUSIONS......Page 1272 MULTIPLE ENDOCRINE NEOPLASIA TYPE 1......Page 1274 MULTIPLE ENDOCRINE NEOPLASIA TYPE 2, TYPE 3, AND FA MILIAL MEDULLARY THYROI D CANCER......Page 1277 MULTIPLE ENDOCRINE NEOPLASIA TYPE 4......Page 1279 MULTIPLE ENDOCRINE NEOPLASIA TYPE 1......Page 1281 MULTIPLE ENDOCRINE NEOPLASIA TYPE 2......Page 1282 PHOSPHATASE AND TENSIN HOMOLOG ON CHRO MOSOME 10......Page 1283 SDHX/TMEM127/MAX......Page 1284 VON HIPPEL-LINDAU AND PHEOCHRO MOCYTO MA......Page 1285 TRANSLOCATION-ASSOCIATED SOFT TISSUE SARCOMAS......Page 1288 COMPLEX SOFT TISSUE SARCOMA TYPES......Page 1294 CARTILAGINOUS TUMORS......Page 1296 OSTEOSARCOMA......Page 1297 FUTURE DIRECTIONS: NEXT-GENERATION SEQUENCING AND FUNCTIONAL SCREENS......Page 1298 INCIDENCE AND ETIOLOGY......Page 1300 ANATOMIC AND AGE DISTRIBUTION AND PATHOLOGY......Page 1301 DIAGNOSIS AND STAGING......Page 1313 MANAGE MENT BY PRESENTATION STATUS, EXTENT OF DISEASE, AND ANATOMIC LOCATION......Page 1317 PALLIATIVE CARE......Page 1336 FUTURE DIRECTIONS......Page 1337 INCIDENCE AND ETIOLOGY......Page 1339 ANATOMY AND PATHOLOGY......Page 1340 DIAGNOSIS......Page 1341 MANAGEMENT BY DIAGNOSIS AND STAGE......Page 1344 CONTINUING CARE: SURVEILLANCE AND PALLIATION......Page 1357 GENERAL APPROACH TO MANAGEMENT OF SKIN CANCER......Page 1361 TOPICAL THERAPY FOR SKIN CANCER......Page 1364 CLINICAL FEATURES OF ACTINIC KERATOSIS......Page 1365 TREATMENT OF ACTINIC KERATOSIS......Page 1366 Basal Cell Carcinoma......Page 1367 BASAL CELL CARCINOMA SUBTYPES......Page 1368 HISTOLOGY......Page 1369 Squamous Cell Carcinoma......Page 1370 CLINICAL FEATURES OF SQUAMOUS CELL CARCINOMA AND ITS VARIANTS......Page 1371 CLINICAL BEHAVIOR OF SQUAMOUS CELL CARCINOMA......Page 1372 TREATMENT......Page 1373 IMMUNOSUPPRESSION AND NONMELANOMA SKIN CANCER......Page 1374 TREATMENT......Page 1375 HISTOLOGY......Page 1376 CLINICAL PRESENTATION......Page 1377 RECURRENCE AND METASTATIC RISK......Page 1378 Sebaceous Carcinoma......Page 1379 Atypical Fibroxanthoma And Malignant Fibrous Histiocytoma......Page 1380 Carcinoma Metastatic to Skin......Page 1381 THE RAS-RAF-MAP KINASE PATHWAY......Page 1384 THE MEPK PATHWAY AND THERAPEUTIC RESISTANCE......Page 1388 MELANIN SYNTHESIS PATHWAY......Page 1390 MOLECULAR GENETICS OF MElaNOMA: LOO KING AHEAD......Page 1391 MOLECULAR BIOLOGY OF MELANOMA......Page 1393 EPIDEMIOLOGY......Page 1396 ANATOMIC DISTRIBUTION......Page 1397 ETIOLOGY AND RISK FACTORS......Page 1398 PREVENTION AND SCREENING......Page 1399 DIAGNOSIS OF PRIMARY MELANOMA......Page 1400 GENERAL CONSIDERATIONS IN CLINICAL MANAGEMENT OF A NEWLY DIAGNOSED CUTANEOUS MELANOMA (STAGE I–II)......Page 1405 CLINICAL TRIALS TO DEFINE MARGINS OF EXCISION FOR PRIMARY CUTANEOUS MELANOMAS......Page 1406 SURGICAL STAGING OF REGIONAL NODES......Page 1407 MANAGEMENT......Page 1410 SPECIAL CONSIDERATIONS IN MANAGEMENT OF PRIMARY MELANOMAS......Page 1412 CLINICAL FOLLOW-UP FOR INTERMEDIATETHICKNESS AND THICK MELANOMAS (STAGE IB–IIC)......Page 1413 REGIONALLY METASTATIC MELANOMA (STAGE III): LYMPH NODE METASTASIS, SATELLITE LESIONS, AND IN-TRANSIT METASTASES......Page 1414 MANAGEMENT OF REGIONAL METASTASES IN PATIENTS WITH VISCERAL OR OTHER DISTANT DISEASE......Page 1417 ADJUVANT SYSTEMIC THERAPY (STAGES IIB, IIC, and III)......Page 1418 MANAGEMENT OF DISTANT METASTASES OF MELANOMA (STAGE IV)......Page 1423 EXPERIMENTAL IMMUNOLOGIC THERAPIES FOR METASTATIC MELANOMA......Page 1433 RADIATION THERAPY FOR METASTATIC MELANOMA (STAGE IV)......Page 1435 HEREDITARY SKIN CANCER AND THE NEUROFI BRO MATO SES......Page 1442 CONCLUSION......Page 1448 GLIOMAS......Page 1450 MENINGIOMAS......Page 1452 MEDULLOBLASTOMAS......Page 1454 EPENDYMAL TUMORS......Page 1456 SUMMARY......Page 1457 EPIDEMIOLOGY OF BRAIN TUMORS......Page 1459 CLASSIFICATION......Page 1460 ANATOMIC LOCATION AND CLINICAL CONSIDERATIONS......Page 1462 NEURODIAGNOSTIC TESTS......Page 1463 SURGERY......Page 1464 RADIATION THERAPY......Page 1465 CHEMOTHERAPY AND TARGETED AGENTS......Page 1467 SPECIFIC CENTRAL NERVOUS SYSTEM NEOPLASMS......Page 1468 OPTIC, CHIASMAL, AND HYPOTHALAMIC GLIOMAS......Page 1476 BRAINSTEM GLIOMAS......Page 1478 GANGLIOGLIOMAS......Page 1479 EPENDYMOMA......Page 1480 MENINGIOMAS......Page 1481 PRIMITIVE NEUROECTODERMAL OR EMBRYONAL CENTRAL NERVOUS SYSTEM NEOPLASMS......Page 1484 PINEAL REGION TUMORS AND GERM CELL TUMORS......Page 1486 PITUITARY ADENOMAS......Page 1488 CRANIOPHARYNGIOMAS......Page 1490 VESTIBULAR SCHWANNOMAS......Page 1491 GLOMUS JUGULARE TUMORS......Page 1492 HEMANGIOBLASTOMAS......Page 1493 CHORDOMAS AND CHONDROSARCOMAS......Page 1494 SPINAL AXIS TUMORS......Page 1496 TUMOR SUPPRESSOR GENES......Page 1503 SDH DEFICIENT GIST......Page 1505 NEUROBLASTOMA......Page 1506 RHABDOMYOSARCOMA......Page 1507 HEREDITARY SYNDROMES ASSOCIATED WITH TUMORS OF CHILDHOOD LI-FRAUMENI SYNDROME......Page 1508 PREDICTIVE TESTING FOR GERM-LINE MUTATIONS AND CHILDHOOD CANCERS......Page 1509 MOLECULAR THERAPEUTICS......Page 1510 NEUROBLASTOMA......Page 1512 WILMS TUMOR......Page 1521 RETINOBLASTOMA......Page 1524 PEDIATRIC BONE SARCOMAS: OSTEOSARCOMA AND EWING SARCOMA......Page 1528 RHABDOMYOSARCOMA......Page 1535 HEPATOBLASTOMA......Page 1539 GERM CELL TUMORS......Page 1542 LEUKEMIAS......Page 1547 LYMPHOMAS......Page 1553 LONG-TERM, PALLIATIVE, AND HOSPICE CARE IN PEDIATRIC ONCOLOGY......Page 1556 THE CELL OF ORIGIN OF LYMPHOMA......Page 1558 GENERAL MECHANISMS OF GENETIC LESIONS IN LYMPHOMA......Page 1560 MOLECULAR PATHOGENESIS OF B-NHL......Page 1562 MOLECULAR PAT HOGENESIS OF T-CELL NON-HODGKIN LY MPHOMA......Page 1569 MOLECULAR PAT HOGENESIS OF HODGKIN LY MPHOMA......Page 1571 BIOLOGY OF HODGKIN’S LYMPHOMA......Page 1573 PATHOLOGY OF HODGKIN’S LYMPHOMA......Page 1574 DIFFERENTIAL DIAGNOSIS......Page 1578 EARLY-STAGE HODGKIN’S LYMPHOMA......Page 1580 ADVANCED-STAGE HODGKIN’S LYMPHOMA......Page 1582 SPECIAL CIRCUMSTANCES......Page 1587 TREATMENT......Page 1588 EPIDEMIOLOGY AND ETIOLOGY......Page 1599 BIOLOGIC BACKGROUND FOR CLASSIFICATION OF LYMPHOID NEOPLASMS......Page 1600 LYMPHOMA CLASSIFICATION: THE PRINCIPLES OF THE WORLD HEALTH ORGANIZATION (WHO) CLASSIFICATION OF LYMPHOID NEOPLASMS......Page 1603 PRINCIPLES OF MANAGEMENT OF NON-HODGKIN’S LYMPHOMA......Page 1605 SPECIFIC DISEASE ENTITIES......Page 1607 MATURE T-CELL AND NATURAL KILLER CELL NEOPLASMS......Page 1621 MYCOSIS FUNGOIDES AND THE SÉZARY SYNDROME......Page 1631 DIAGNOSIS AND STAGING......Page 1633 CLINICAL EVALUATION OF PATIENTS WITH CUTANEOUS LYMPHOMA......Page 1635 PRINCIPLES OF THERAPY OF MYCOSIS FUNGOIDES AND THE SÉZARY SYNDROME......Page 1636 SYSTEMIC THERAPY FOR MYCOSIS FUNGOIDES AND THE SÉZARY SYNDROME......Page 1639 OTHER CUTANEOUS LYMPHOMAS......Page 1641 STAGING......Page 1644 TREATMENT......Page 1645 ELUCIDATION OF GENETIC EVENTS IN ACUTE LEUKEMIA......Page 1649 MUTATIONS THAT TARGET CORE-BINDING FACTOR......Page 1652 CHROMOSOMAL TRANSLOCATIONS THAT TARGET THE RETINOIC ACID RECEPTOR ALPHA GENE......Page 1653 CHROMOSOMAL TRANSLOCATIONS THAT TARGET THE MLL GENE......Page 1654 MUTATIONS OF EPIGENETIC MODIFIERS......Page 1655 POINT MUTATIONS IN ACUTE LEUKEMIA......Page 1656 MUTATIONS IN TUMOR SUPPRESSOR GENES......Page 1657 MUTATION OF LYMPHOID DEVELOPMENT GENES IN ACUTE LYMPHOID LEUKEMIA......Page 1658 MUTATIONAL COMPLEMENTATION GROUPS IN ACUTE LEUKEMIAS......Page 1659 CONCLUSION......Page 1660 INTRODUCTION......Page 1662 ACUTE MYELOGENOUS LEUKEMIA......Page 1663 ACUTELY MPHOBLASTIC LEUKEMIA......Page 1674 CHRONIC MYELOID LEUKEMIA......Page 1684 CHRONIC LYMPHOCYTIC LEUKEMIA......Page 1687 Acknowledgments......Page 1689 PATHOGENESIS......Page 1691 DIAGNOSIS......Page 1692 THERAPY......Page 1693 ADVANCED PHASE DISEASE......Page 1699 MOLECULAR BIOLOGY......Page 1701 DIAGNOSIS......Page 1703 TREATMENT AND RESPONSE CRITERIA......Page 1705 NEW AND NOVEL TREATMENTS FOR CHRONIC LYMPHOCYTIC LEUKEMIA......Page 1713 LARGE GRANULAR LYMPHOCYTE LEUKEMIA......Page 1714 HAIRY CELL LEUKEMIA......Page 1715 EPIDEMIOLOGY......Page 1718 PAT HOGENESIS......Page 171