Primary Central Nervous System Tumors (eBook)

Pathogenesis and Therapy

Andrew D. Norden, David A. Reardon, Patrick C. Y. Wen (Herausgeber)

eBook Download: PDF

2010 | 2011
XIV, 570 Seiten
Humana Press (Verlag)
978-1-60761-166-0 (ISBN)

Infos

This comprehensive, yet practical, text is a ready collection of the most up-to-date information on primary CNS tumors. Authored by a carefully selected group of the world's leading clinicians and scientists, the book is divided into three sections. The opening chapters cover general principles, including epidemiology, pathogenesis, tumor stem cells, supportive care, complications of therapy, and quality of life. The remaining two sections are comprised of treatment-oriented chapters covering the spectrum of gliomas and rarer tumor types. Each of these chapters presents multi-disciplinary therapeutic approaches and addresses specific disease concerns. Throughout, the authors incorporate the cutting-edge advances in molecular biology and genomics that are revolutionizing neuro-oncology. The result is an important clinical resource which provides evidence-based data and interpretation essential to intelligent therapeutic decision making.

Inhalt

Preface 6
Contents 7
Contributors 9
Part I General Principles 14
1 Epidemiology and Risk Factors 15
Introduction 15
Gliomas 16
Population Epidemiology 16
Survival and Prognosis 17
Risk Factors 19
Hormonal and Reproductive Factors 19
Ionizing Radiation 20
Cellular Telephone Usage 20
Other Possible Environmental or Behavioral Risk Factors 21
Genetic Factors 22
Familial Aggregation 22
Polymorphisms in Genes Relevant to Cancer 23
Infections and Immunologic Factors 24
Meningiomas 25
Population Epidemiology 25
Exogenous Risk Factors 26
Ionizing Radiation 26
Hormones 26
Association with Breast Cancer 28
Head Trauma 28
Family History 28
Genetic Polymorphisms 29
Conclusion 29
References 30
2 Molecular Pathogenesis 38
Introduction 38
Gliomas 39
Low-Grade and Intermediate-Grade Gliomas 39
Diffuse Astrocytoma, WHO Grade II 39
Anaplastic Astrocytoma 41
Oligodendroglioma and Anaplastic Oligodendroglioma 42
Glioblastoma 42
Secondary GBM 42
Primary GBM 43
Key Functional Pathways in Glioma Pathogenesis 43
Molecular Classification and Clinically Relevant Subtypes of Glioblastoma 46
Prognostic and Predictive Markers 49
Cell of Origin and the Tumor Stem Cell Hypothesis 49
Mouse Models 49
Tumor Stem Cells 50
References 51
3 Cellular Origins of Malignant Glioma: The Cancer Stem Cell Polemic 56
Introduction 56
Glioma Stem Cells 58
Glioma Stem Cell Caveats 59
Astrocytes or Astrocyte Progenitors as Cell of Origin for Glioma 60
''Restricted'' Neural Progenitors as Cell of Origin for Glioma 61
Multipotent Neural Progenitors as Cell of Origin 61
Conclusion 62
References 62
4 Principles of Supportive Care 65
Cerebral Edema 65
Complications of Corticosteroids 69
Gastrointestinal Complications 69
Musculoskeletal Complications 70
Psychiatric Complications 71
Immunosuppressive Effects and Infectious Complications of Corticosteroids 71
Other Steroid Side Effects 73
Novel Therapies for Cerebral Edema 73
Seizures 73
Epidemiology and Pathophysiology 73
Prophylactic Treatment 74
AED Interactions with Antineoplastic Agents 75
Surgical Management of Seizures 78
Thromboembolic Complications 78
Epidemiology and Pathophysiology 78
Diagnosis 79
Prophylactic Treatment 79
Symptomatic Treatment 80
Intracranial Hemorrhage 82
Neurocognitive Symptoms 82
Fatigue 82
Cognitive Impairment 83
Depression and Anxiety 84
Summary 84
References 85
5 Principles of Clinical Trial Design and Response Assessment 95
Introduction 95
Phase 0 Trials 96
Phase I Trials 98
Cytotoxic Agents 98
Novel Agents 100
Limitations 101
Phase II Trials 101
Cytotoxic Agents 101
Novel Agents 102
Secondary Evaluations 103
Limitations 103
Phase III Clinical Trials 104
Special Challenges of Brain Tumor Trials 104
Drug Selection 104
Neuropathology 105
Response Assessment and Endpoints 106
Historical Controls 108
Conclusion 109
References 109
6 Complications of Therapy 113
Pharmaceutical Therapy 113
Systemic Therapies 114
Conventional Chemotherapeutic Agents 114
Molecularly Targeted Agents 125
Anti-epileptic Therapy Issues 126
Local/Regional Therapies 126
Complications After Radiation Therapy for CNS Neoplasms 127
Introduction 127
Acute Toxicities 128
Fatigue 128
Local Symptoms 128
Craniospinal Axis Radiation 129
Subacute Toxicity 130
Pseudoprogression 130
Somnolence Syndrome 133
Lhermitte's Sign 133
Neurologic Late Toxicity 133
Brain Necrosis 134
Spinal Cord Myelopathy 134
Optic Neuropathy 135
Ototoxicity 136
Other Cranial Nerve Injury 136
Stroke-Like Migraine Attacks 137
Multiple Sclerosis-Related Toxicity 138
Non-neurologic Late Toxicity 138
Endocrinopathy 139
Vasculopathy 139
Secondary Neoplasm 139
Conclusion 140
References 141
7 Neuropsychological Function and Quality of Life 152
Neurocognitive Function 152
Impact of the Tumor on Neurocognitive Function 153
Treatment Effects 154
Effects of Adjuvant Medications and Medical Complications 155
Patient Care and Management 156
Neurocognitive Interventions and Pharmacotherapy 156
Neurocognitive Interventions 157
Pharmacotherapy 157
Methylphenidate 157
Modafinil 160
Donepezil 160
Alpha-Tocopherol (Vitamin E) 161
Symptoms and Quality of Life in Brain Tumor Patients 162
Overview of QOL and Symptoms 162
Overview of Common Symptoms 163
Fatigue 163
Pathophysiology/Etiologic Contributors and Assessment 164
Interventions 165
Mood Disturbance 166
Pathophysiology/Etiology and Assessment 167
Interventions 168
New Paradigms: Sleep--Wake Cycle Disturbance and Symptom Clusters 169
Impact on the Patient and Family 169
Conclusions 169
References 170
Part II Gliomas 180
8 Low-Grade Gliomas 181
Epidemiology 181
Pathology and Pathogenesis 182
Astrocytic Tumors 182
Molecular Genetics of Low-Grade Gliomas 184
Clinical Presentations 186
Imaging 186
Prognostic Factors 188
Surgical Management 189
Innovations in Surgical Management of Gliomas 191
Radiation Therapy 193
Chemotherapy 195
Conclusions 196
References 196
9 High-Grade Astrocytomas 203
Introduction 203
Epidemiology 204
Pathology and Pathogenesis 204
Management of Newly Diagnosed High-Grade Astrocytomas 209
Surgical Management 209
Carmustine Wafers 209
Radiation Therapy 210
Chemotherapy 211
Temozolomide 211
HGA in the Elderly 214
Management of Recurrent HGA 215
Diagnosis of Recurrence 215
Surgical Resection 216
Locoregional Therapy 217
Re-irradiation 217
Salvage Chemotherapy 218
Novel Treatment Approaches 219
Molecularly Targeted Therapy 219
Anti-angiogenic Therapy 223
Other Molecular Targets 227
Other New Treatment Approaches 228
Conclusions 229
References 229
10 Anaplastic Oligodendrogliomas and Mixed Gliomas 241
Introduction 241
Incidence, Clinical Presentation, Localization 242
Pathology and Genetics 242
Histology 242
Genetics 244
Diagnosis 245
Prognosis 247
Histology 247
Genotype 247
Clinical Characteristics 247
Treatment 247
Surgery 248
Radiotherapy 248
Chemotherapy 248
Chemotherapy at Recurrence 249
Adjuvant Chemotherapy in Newly Diagnosed AOT 251
Upfront Chemotherapy in Newly Diagnosed AOT 252
References 253
11 Ependymomas 257
Introduction 257
Pathology and Classification 259
Prognostic Factors 259
Incidence and Epidemiology 260
Molecular Profiles 261
Chromosomal Abnormalities 261
Molecular Pathway Abnormalities 262
Gene Array-Based Profiles 262
Epigenetic Studies 262
Ependymoma Stem Cells 263
Implications for Prognosis and Treatment 263
Treatment 263
Intracranial Tumors 263
Spinal Cord Ependymomas 265
Future Directions 266
Conclusions 266
References 267
12 Uncommon Gliomas in Adults: Brainstem Gliomas, Pilocytic Astrocytomas, and Pleomorphic Xanthoastrocytomas 271
Introduction 271
Epidemiology 271
Clinical Presentation/Diagnosis 273
Pathology/Classification 274
Prognostic Factors 275
Treatment 275
Diffuse Tumors 275
Focal Tumors 277
Pilocytic Astrocytoma 278
Introduction 278
Epidemiology 278
Clinical Presentation/Diagnosis 278
Pathology/Classification 279
Prognostic Factors 280
Treatment 281
Pleomorphic Xanthoastrocytoma 281
Introduction 281
Epidemiology 281
Clinical Manifestations/Diagnosis 282
Pathology/Classification 283
Prognostic Factors 283
Treatment 284
References 284
Part III Other Tumor Types 291
13 Pediatric Tumors 292
Epidemiology 292
Pediatric Brain Tumors and Genetic Syndromes 293
Presentation of Pediatric Central Nervous System Tumors 296
Direct Compression of Brain Tissue 296
Obstructive Hydrocephalus Causing Increased Intracranial Pressure 297
Gliomas 297
Glioma Location Often Predicts Presentation 298
Supratentorial and Cerebellar Astrocytomas 298
Optic Pathway/Hypothalamic Gliomas 298
Thalamic Gliomas 298
Midbrain and Brainstem Astrocytomas 299
Glioma Grade Often Predicts Prognosis and Treatment 299
Low-Grade Astrocytomas 299
High-Grade Astrocytomas 301
Imaging 302
Histology 304
Treatment 305
Ependymoma 307
Embryonal Tumors 310
Medulloblastoma 310
Supratentorial PNET 314
Pineoblastoma 314
Choroid Plexus Tumors 315
Germ Cell Tumors 317
Craniopharyngioma 320
Late Effects 321
Surgery 322
Radiation Therapy 322
Chemotherapy 323
References 324
14 Primary Central Nervous System Lymphoma 340
Primary CNS Lymphoma 340
Pathobiology 340
Clinical Features 341
Diagnostic Evaluation 342
Neuroimaging 344
Prognostic Markers 345
Treatment of Immunocompetent Patients with PCNSL 346
Corticosteroids 346
Radiation 346
Combined Modality Therapy 347
Chemotherapy Alone 351
Intrathecal Chemotherapy 352
High-Dose Chemotherapy with Stem Cell Rescue 352
Salvage Therapy 352
Neurotoxicity 353
Treatment of HIV-Related PCNSL 354
References 355
15 Meningiomas 361
Historical Perspective and Epidemiology 361
Clinical Presentation 362
Neuroradiology 362
Pathology and Molecular Genetics 365
Natural History 368
Treatment 369
Surgery 369
Radiotherapy 371
Hormonal Therapy 371
Biochemotherapy 372
Targeted Therapy 373
Conclusions 375
References 377
16 Pituitary Adenomas 382
Epidemiology 382
Pathogenesis 383
Classification 384
Clinical Presentation 387
Functional Pituitary Tumors 388
Diagnosis 390
Endocrine Testing 390
Imaging 391
Medical Therapy 392
Pituitary Hormone Replacement 392
Surgical Treatment 395
Radiation Therapy and Radiosurgery 397
Prognosis 398
Quality of Life 398
Conclusions 399
References 399
17 Vestibular Schwannomas 406
Introduction 406
Observation 408
Surgical Resection 410
Radiotherapy 412
Chemotherapy 414
Conclusion 415
References 415
18 Medulloblastomas 419
Introduction 419
Incidence 419
Survival 420
Risk Factors 421
Pathology and Biology 421
Diagnosis 423
Staging 423
Prognosis 423
Treatment 425
Neurosurgery 426
Radiation Therapy 426
Quality of Radiation Therapy 427
Chemotherapy 428
Standard-Risk Medulloblastoma 428
High-Risk Medulloblastoma 431
General Recommendations for the Management of Medulloblastoma 432
Late Sequelae 433
Long-Term Sequelae 433
Follow-Up 434
References 434
19 Pineal Region Tumors 438
Introduction 438
Brief History of the Pineal Gland 438
Anatomy and Physiology of the Pineal Gland 438
Overview of Tumors of the Pineal Region 439
Presentation of Pineal Tumors 440
Germ Cell Tumors: Pathology and Diagnosis 440
Imaging 440
Pathology and Immunohistochemistry of Germ Cell Tumors 441
Germinomas 441
Teratomas 441
Yolk Sac Tumor 442
Embryonal Carcinomas 442
Choriocarcinomas 442
Genetics of Germ Cell Tumors 442
CSF and Serum Analysis of Germ Cell Tumors 443
Prognosis of Germ Cell Tumors 443
Pineal Parenchymal Tumors: Pathology and Diagnosis 443
Imaging 444
Pathology of PPTs 444
Pineocytomas 444
Pineoblastomas 445
Pineal Parenchymal Tumor of Intermediate Differentiation 445
Genetics of PPTs 446
Prognosis 446
Miscellaneous Tumor Types 446
Glioma 446
Meningioma 447
Papillary Tumor of the Pineal Region 447
Metastases to the Pineal Gland 447
Treatment of Pineal Region Tumors 448
Treatment of Hydrocephalus 448
Treatment of Germ Cell Tumors 448
Germinomas 448
Non-germinomatous Germ Cell Tumors 450
Treatment of Pineal Parenchymal Tumors 450
Pineocytomas 450
Pineoblastomas 451
Pineal Parenchymal Tumors of Intermediate Differentiation 453
Pineal Gliomas 453
Meningiomas 453
Ependymomas 454
Conclusion and Future Directions 454
References 455
20 Genetic Syndromes 459
Introduction 459
Neurofibromatosis 461
Overview 461
Epidemiology 461
Clinical Genetics 461
Molecular Genetics and Pathogenesis 462
NF1, Neurofibromin 462
Mutations 462
Genetic Testing 462
Clinical Features 463
Diagnostic Criteria 463
Developmental Expression of Phenotype 463
Associated Tumors 463
Neurofibromas 463
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) 464
Gliomas 465
Management 465
Neurofibromas 466
MPNSTs 466
Glioma 467
Future Directions 467
Neurofibromatosis 468
Overview 468
Epidemiology 468
Clinical Genetics 468
Molecular Genetics and Pathogenesis 469
Mutations 469
Genetic Testing 469
Clinical Features 469
Diagnostic Criteria 469
Associated Tumors 470
Management 470
Initial Evaluation 470
Subsequent Evaluation 471
Future Directions 472
Tuberous Sclerosis Complex 472
Overview 472
Epidemiology and Clinical Genetics 473
Molecular Genetics and Pathogenesis 473
Clinical Features 473
Presentation 473
Diagnostic Criteria 473
Genetic Testing 474
Screening 474
Associated Tumors 474
Cortical Tubers 475
Subependymal Nodules 475
SEGAs 475
Other Malignancies 476
Prognosis and Future Directions 477
Von Hippel-Lindau Disease 477
Overview 477
Clinical Overview 477
Epidemiology and Clinical Genetics 477
Molecular Genetics and Pathogenesis 478
VHL, pVHL 478
Mutations 478
Clinical Features 478
Diagnostic Criteria 478
Genetic Testing 479
Screening 479
Associated Tumors 479
CNS Hemangioblastoma 479
Other Malignancies 481
Prognosis 482
Future Directions 482
Cowden Syndrome 482
Overview 482
Molecular Genetics and Pathogenesis 483
Clinical Features 483
Diagnostic Criteria 483
Associated Tumors: LDD 484
Management 485
Li- 
485 
Overview 485
Molecular Genetics and Pathogenesis 485
Clinical Features 485
Presentation 485
Diagnostic Criteria 486
Management 486
Turcot Syndrome 486
Overview 486
Clinical Presentation 486
Molecular Genetics and Pathogenesis 487
Diagnostic Criteria 487
Management 487
Gorlin Syndrome 488
Overview 488
Molecular Genetics and Pathogenesis 488
Clinical Features 488
Presentation 488
Diagnosis 489
Management 489
References 489
21 Rare Tumors 500
Introduction 500
Tumors of Neuroepithelial Tissue 500
Choroid Plexus Tumors 500
Choroid Plexus Papillomas 501
Choroid Plexus Carcinoma 501
Neuronal and Mixed Neuronal--Glial Tumors 502
Ganglioglioma and Gangliocytoma 502
Desmoplastic Infantile Astrocytoma and Desmoplastic Infantile Ganglioglioma 503
Dysplastic Gangliogliocytoma of the Cerebellum (Lhermitte--Duclos disease) 503
Cerebellar Liponeurocytoma 504
Central Neurocytoma and Extraventricular Neurocytoma 504
Papillary Glioneuronal Tumor 505
Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle 506
Dysembryoplastic Neuroepithelial Tumor 506
Intracranial and Intraspinal Paraganglioma 506
Embryonal Tumors 507
CNS Primitive Neuroectodermal Tumors 508
Supratentorial Primitive Neuroectodermal Tumor 508
Ependymoblastoma 509
Medulloepithelioma 509
CNS Ganglioneuroblastoma 509
CNS Atypical Teratoid/Rhabdoid Tumors 510
Other Neuroepithelial Tumors 510
Astroblastoma 510
Chordoid Glioma of the Third Ventricle 511
Angiocentric Glioma 511
Tumors of the Meninges 511
Mesenchymal Tumors 511
Tumors of Adipose Tissue 511
Intracranial Lipoma 511
Central Nervous System Angiolipoma 512
Central Nervous System Hibernoma 512
Liposarcoma 513
Fibrous Tumors 513
Solitary Fibrous Tumor 513
Fibrosarcoma 514
Malignant Fibrous Histiocytoma 514
Tumors of Cartilaginous Tissue: Chordoma, Chondrosarcoma 514
Primary Meningeal Hemangiopericytoma 515
Ewing--s Sarcoma -- Primitive Neuroectodermal Tumor 516
Primary Melanocytic Lesions 516
Primary Malignant Melanoma of the Central Nervous System 516
Melanocytoma 517
Melanocytosis and Melanomatosis 517
Cystic Lesions 517
Epidermoid Cyst 518
Dermoid Cyst 518
Colloid Cyst 518
Arachnoid Cyst 519
References 519
22 Spinal Tumors 530
Incidence and Prevalence of Primary Neoplasms of the Spine 530
Anatomical Distribution 531
Epidural Tumors 531
Intradural--Extramedullary Spinal Cord Tumors 531
Intramedullary Spinal Cord Tumors 532
Diagnostic Utilities 532
Imaging Studies 532
Biopsy 533
Laboratory Studies 533
Presentation, Diagnosis, and Management 534
Main Types of Epidural Spinal Cord Tumors 534
Chordomas 534
Chondrosarcomas 536
Osteosarcomas 538
Ewings Sarcoma and Peripheral Neuroectodermal Tumor 539
Multiple Myeloma and Plasmacytomas 540
Other Spinal Epidural Tumors 541
Intraspinal Extramedullary Spinal Cord Tumors 542
Presentation 542
Diagnosis 542
Types of Tumors 542
Prognosis and Management 543
Intramedullary Spinal Cord Tumors (ISCTs) 544
Presentation 544
Diagnosis 544
Main Types of Tumors 544
Prognosis and Management 546
References 547
Index 549

Produkt-Details

• Erscheint lt. Verlag: 15.12.2010
• Reihe/Serie: Current Clinical Oncology
• Reihe/Serie: Current Clinical Oncology
• Zusatzinfo: XIV, 570 p.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Chirurgie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Themenwelt: Medizinische Fachgebiete ► Radiologie / Bildgebende Verfahren ► Radiologie
• Schlagworte: Astrocytoma • brain tumor • Chemotherapy • CNS lymphoma • Ependymoma • Glioma • Hemangioblastoma • Medulloblastoma • Meningioma • neurosurgery • Oligodendogliomas • Pituitary adenoma • radiation therapy • Radiaton Oncology • Schwannoma
• ISBN-10: 1-60761-166-X / 160761166X
• ISBN-13: 978-1-60761-166-0 / 9781607611660