Therapy of Malignant Brain Tumors

515 Pages·1986·36.832 MB·English

by  Prof. Dr. K. Jellinger (auth.), Prof. Dr. Kurt Jellinger (eds.)

Therapy of Malignant
Brain Tumors
Edited by
Kurt Jellinger
Springer-Verlag Wien New York
Prof. Dr. Kurt JeUinger
Ludwig Boltzmann Institute of Clinical Neurobiology
Lainz Hospital, Vienna, Austria
This work is subject to copyright.
All rights are reserved, whether the whole or part of the material is concerned, specifically those of
translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or
similar means, and storage in data banks.
© 1987 by Springer-Verlag/Wien
Softcover reprint of the hardcover 1st edition 1987
Product Liability: The publisher can give no guarantee for information about drug dosage and
application thereof contained in this book. In every individual case the respective user must check its
accuracy by consulting other pharmaceutical literature.
With 111 Figures
ISBN-13: 978-3-7091-8878-1 e-ISBN-13: 978-3-7091-8876-7
DOl: 10.1007/978-3-7091-8876-7
Foreword
The tumors of the brain similar to other pathological changes of that particular
organ claim for a separate position in scientific medicine regarding biology,
morphology, features of clinical manifestation, diagnostics and therapy. During the
past years due to rapid progress in basic neurosciences and medical biotechnics the
situation of the neuroclinician in front of brain tumors has been dramatically
changed. The prerequisites for early and accurate diagnosis as well as for successful
treatment also of malignant neoplasms have increased and remarkably improved.
At the same time the information necessary for an appropriate pragmatic use of the
available cognitive methods and therapeutic means increased along the same scale
and is permanently being critically modified or changed due to fundamental new
insights which come up in always shorter intervals. These facts necessitate the
preparation of publications in which the state of the art is presented in possible
completeness, systematic order and proper disposability for rational management
and therapeutic strategies.
The primary aim of the present book is to serve these purposes. With 8 chapters
the collective of competent authors deal on the biology, pathology and immunology
of malignant brain tumors of adults and of children including relevant basic and
recent data of experimental research; further on the available methods of therapy:
neurosurgery, radiology and chemotherapy, the fundamental principals of their
efficacy and the differing models of single respective combined application, in
comprehensive critical form. In all contributions a well-matched balance and
complementarity between mediation of the relevant basic knowledge and in
formation about the given practical experiences and results of thorough evaluation
is achieved. The present publication appears suitable to promote future competent
management and broader better results in the complex field of multimodal brain
tumor therapy.
For the exemplary realization of the challenging concept of this book which
also presents an equally high standard of contributions from the scientific and the
didactic point of view, the editor, Prof. Dr. K. Jellinger, merits great appreciation.
I would like to wish this publication the proper full success through all field ofthe
clinical neurosciences.
Vienna, November 1986 F. Seitelberger
Contents
1 Pathology of Human Intracranial Neoplasia .
By K. Jellinger
I. Introduction. . . . . . . . . . . . . . . . 1
II. Basic Principles of Neurooncology .. : 2
1. General Biology of Brain Tumors. 2
2. Microvasculature and Blood-Brain Barrier (BBB) 5
3. Immunological Responses 7
III. Classification and Grading. 9
IV. Epidemiology. . . . . . . . . . 23
V. Special Neurooncology. . . . . 24
I. Tumors of Neuroepithelial Tissue . 24
A. Glial Tumors or Gliomas . . 27
1. Astrocytic Tumors. . . . . 27
2. Oligodendroglial Tumors . 35
3. Ependymal Tumors . . . . 36
4. Mixed Gliomas . . . . . . 38
5. Glioblastomatous Tumors 39
6. Choroid Plexus Tumors. 42
B. Pineal Cell Tumors. 43
C. Neuronal Tumors . . . . . 44
D. Embryonal Tumors . . . . 45
1. "Primitive" Neuroectodermal Tumors NOS. 47
2. PNET with Differentiation . . . . . .. . . . 47
3. Medulloblastoma, NOS, and with Differentia JOn 48
2. Tumors of Nerve Sheath (Nerve Sheath Cells) . 51
A. Neurilemmoma.. . . . . . . . . . 52
B. Neurofibroma . . . . . . . . . . . . . . . . 52
C. Anaplastic Nerve Sheath Tumors. . . . . . 52
3. Tumors of Meningeal and Related (Mesenchymal) Tissues 53
A. Meningiomas. . . . . . . . 53
1. Meningioma NOS. . . . 53
2. "Papillary" Meningioma 54
3. Anaplastic Meningioma. 54
4. Meningio-Angiomatosis . 54
B. Primary Melanocytic Tumors . 55
C. Meningeal Sarcomatous Tumors 56
1. Meningeal Sarcoma and Primary Meningeal Sarcomatosis. 56
2. Fibrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . 56
3. Sarcoma with Glio{blastomatous) Component ("Sarcoglioma"). 56
4. Rhabdomyosarcoma and Leiomyosarcoma . 56
5. Mesenchymal Chondrosarcoma 56
6. Xanthosarcoma . . . . . . . . . . . . . . . . 57
VIII Contents
4. Primary Malignant Lymphomas. 57
5. Tumors of Blood Vessel Origin 58
A. Hemangioblastoma. . . . . . 58
B. Hemangiopericytoma . . . . 58
C. Neoplastic "Angioendotheliosis (Angioendotheliomatosis)"-
Intravascular Lymphomatosis. 59
6. Germ Cell Tumors . . . . . 59
A. Germinoma........ . . . 59
B. Embryonal Carcinomas . . . . 60
C. Choriocarcinoma and Endodermal Sinus Tumor 60
D. Teratomas. . . . . . 60
7. Malformative Tumors. . 60
A. Craniopharyngioma 61
B. Rathke Cleft Cyst . 61
C. Epidermoid and Dermoid Cyst . 61
D. Colloid Cysts of the Third Ventricle (Paraphyseal) or Neuroepithelial
Cyst. . . . . . . . . . . . . . . . . . 61
E. Enterogenous and Respiratory Cyst 62
F. Other Cysts. . . . . . . . . . . . . . 62
G. Lipoma. . . . . . . . . . . . . . . . 62
H. Granular Cell Tumors (Choristoma) . 62
I. Hamartomas.............. 62
1. Hypothalamic Neuronal Hamartoma 62
2. Glial Hamartoma . . . . . . . 63
3. Meningioangioneurinomatosis 63
8. Tumors of Neuroendocrine Origin. 63
A. Pituitary Tumors. . . . 63
I. Pituitary Adenomas . . . . . 63
2. Pituitary Carcinoma. . . . . 64
9. Local Extension from Regional Tumors 64
A. Chemodectoma (Paraganglioma) . . 64
B. Chordoma . . . . . . . . . . . . . . 64
C. Chondroma, Osteochondroma, Chondrosarcoma . 64
D. Olfactory Neuroblastoma (Esthesioneuroblastoma) . 65
10. Metastatic Tumors . 65
II. Unclassified Tumors 66
References . . . . . . . . . . . . 67
2 Neurosurgery of Malignant Brain Tumors 91
By D. Voth
I. Introduction and Historical Retrospect. . . . . . . . . . . . . . . 91
II. General Neurosurgery . . . . . . . . . . . . . . . . . . . ..... 91
a) Diagnosis by Means of Noninvasive and Invasive Measures. 91
I. Methods for Measurements of Intracranial Pressure 93
2. Ventriculography with Positive Contrast Medium. 94
3. CT-controlled Stereotactic Tumor Biopsy ..... . 95
b) Preoperative and Postoperative Monitoring ...... . 96
c) Associated Peri operative Procedures and Palliative Operations. 96
1. Ventriculo-atrial Drainage. . . . . . . . . . . . . . .. 96
2. Ventriculo-peritoneal Drainage ............ . 98
3. Ventriculo-cisternal Drainage (Interventriculostomy) . 100
Contents IX
4. Ventriculo-cisternal Drainage. . . . 102
5. Implantation of an Ommaya Reservoir 102
6. Preliminary Ventricular Drainage. . . . 103
7. Perioperative Administration of Antibiotics. 103
d) General Operative Technique. 104
e) Special Technical Aids. . . . . . . . . 107
I. The Operating Microscope . . . . 107
2. Use of the Laser in Neurosurgery 108
3. Electrocoagulation......... 108
4. The Use of Ultrasound . . . . . . 108
5. Microsurgical Instruments and Suture Material. 108
III. Special Neurosurgery. . . . . . . . . . . 108
a) Tumors of the Supratentorial Space 109
Tumors of the Cerebral Hemisphere 109
Intraventricular Lesions . . . . . 110
Midline Intrinsic Brain Tumors. . . 112
b) Tumors of the Posterior Fossa . . . 113
IV. Significance of the Surgical Measures and Critical Assessment of Their Results 119
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 121
3 Neurosurgical Interventions for lntracranial Metastases . 130
By D. Voth
Introduction . . . . . . . . 130
Data on the Morbidity . . 130
Indications for Operation . 131
Operative Technique. 131
Results of Operation. 132
References . . . . . . 132
4 Stereotactic Biopsy and Technique of Implantation (Instillation)
of Radionuclids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
By F. Mundinger
1. Biopsy for Differentiation ofIntracranial Processes and Optimization of Therapy 134
a) Technique of CT (MRI) Stereotaxy for Biopsy and Implantation of
Radioisotopes . . . . . . . 136
b) Technique of Biopsy . . . . . . . . . 141
c) Clinical Results of Biopsy. . . . . . . 144
d) Consecutive Procedures After Biopsy 145
2. Curie (Brachy-Curie) Therapy (BCiT) . . 147
a) Radiobiology of the Low-Dose Rate CiT. 150
b) Radiobiology of High-Dose Rate Brachy-Curie Therapy (BCiT) 152
3. Techniques of Implantation of Radionuc1ides. . 154
a) Curie Therapy. . . . . . . . . . . . . . . . . 154
b) Technique of Brachy-Curie Therapie (BCiT) 157
c) Contact Radiation Devices. 158
4. Results of BCiT . . . . . . . . . . . . . . . 164
5. New Results of BCiT . . . . . . . . . . . . 170
6. The Place of BCiT in the Treatment Plan . 177
7. Indications for Curie (Brachy-Curie) Therapy and Combined Radiotherapy. 182
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
x Contents
5 Radiation Therapy of Brain Tumors. 195
By R. Sauer
1. Introduction.................... 195
2. Fundamentals of Radiotherapy. . . . . . . . . . 196
2.1 Radiation Sensitivity and Radioresistance 196
2.2 Types of Radiation. 198
2.3 Radiation Dose. . . . . . . . . . . . . . . 199
2.3.1 Definitions............. 199
2.3.2 The Effect of the Dose on Tumor Control 199
204 Treatment Volume . . . . . . . . . 200
204.1 Glioblastoma Multiforme . 200
204.2 Medulloblastoma..... 201
204.3 Ependymoma ..... ~ . . 201
20404 Pineal Tumors and Suprasellar Germinomas 201
2.5 Dose per Fraction. . . . . . . . . . 202
2.5.1 Hyperfractionation.......... 202
2.5.2 Accelerated Fractionation. . . . . . 202
2.5.3 Acceleration by Hyperfractionation 203
2.6 Chemical Radiosensitizers . . . . 203
2.7 Hypoxic Cell Radiosensitizers . . 204
2.8 Heavy Particle Beam Irradiation. 205
2.9 Hyperthermia........... 206
2.10 Brachytherapa (Permanent and Removable Radioactive Implants). 206
2.11 Focal Radiosurgery. . . . . . . . . . . . . . . . . . . . . . . . . . . 207
3. Radiotherapeutic Technique . . . . . 207
3.1 Radiation Treatment Planning. 207
3.1.1 Typing and Grading. 207
3.1.2 Tumor Volume. 208
3.1.3 Target Volume. . . . 209
3.1.4 Dosimetry...... 209
3.1.5 Simulation and Localization of the Treatment Portals. 210
3.2 Technical Setting Devices. . . . . . . . . . 210
3.3 Interstitial Brachytherapy Technique . . . 213
3.3.1 Erlangen Implantation Technique 214
3.3.2 Temporary Implantation 215
3.3.3 Permanent Implantation. 215
4. Special Radiotherapy of Brain Tumors 217
4.1 Low-Grade Astrocytomas. . . . 217
4.2 High-Grade Astrocytomas (Glioblastomas). 217
4.3 Oligodendrogliomas.............. 221
404 Unbiopsied Tumors (Deep-seated Unverified Tumors) 221
4.5 Tumors of the Brain Stem . . . . . . . . . . . . . . 222
4.6 Pineal Tumors and Suprasellar Germinomas. . . . 223
4.7 Cerebral and Cerebellar Astrocytomas in Children 2.25
4.8 Medulloblastoma.. 226
4.9 Ependymoma................... 230
4.10 Pituitary Adenomas. . . . . . . . . . . . . . . . 231
4.10.1 GH-secreting Adenomas (Acromegaly) 232
4.10.2 ACTH-secreting Adenomas (Cushing's Syndrome) . 235
4.10.3 Nelson's Syndrome (NS) . . . . . . . . . . . . 235
4.1004 Prolactin-secreting Adenomas (Prolactinomas) . . . 235
Contents XI
4.10.5 Hormonally Inactive Adenomas and Giant Adenomas. 237
4.11 Craniopharyngioma. 240
4.12 Optic Gliomas .. 242
4.13 Meningiomas . . . . 245
4.14 Brain Metastases . . 245
5. Complications of Radiotherapy. 250
5.1 Definition..... .... 250
5.l.l Acute Reaction .. 250
5.1.2 Early Delayed Reaction. 250
5.1.3 Late Reaction ..... 252
5.2 Incidence of Radiation Injuries 253
5.3 Symptomatology ....... . 253
5.3.1 Acute Reaction .... . 253
5.3.2 Early Delayed Reaction. 253
5.3.3 Late Delayed Reaction 254
5.3.3.1 Brain ..... . 254
5.3.3.2 Spinal Cord .. . 255
5.4 Radiation Tolerance of the Central Nervous System. 255
5.4.1 Radiation Dose ... 256
5.4.l.l Brain.... 256
5.4.1.2 Spinal Cord. 258
5.4.2 Radiation Volume .. 258
5.4.3 Interaction with Chemotherapeutics. 258
5.5 Conclusions. 259
References . . . . . . . . . . . . . . . . . . . . . . . . 259
6 Principles of Chemotherapy in Brain Neoplasia 277
By Mary K. Gumerlock and E. A. Neuwelt
I. Introduction. . . 277
II. Basic Principles. . . . . . 277
A. Cell Cycle . . . . . . 277
B. Tumor Cell Kinetics. 278
C. Anatomic Considerations . 279
D. Prognostic Factors in Brain Tumors. 281
E. Cancer Pharmacokinetics . . 282
F. Chemotherapeutic Principles 283
G. Drug Classifications ... 283
III. Specific Therapeutic Agents . 286
A. Alkylating Agents . . . . 286
1. Nitrogen Mustards . 286
a) Cyclophosphamide 286
b) Mechlorethamine 287
c) Melphalan .. 287
d) Chlorambucil 288
2. Dacarbazine.. 288
3. Nitrosoureas .. 288
4. Streptozotocin. 290
5. Thiotepa .... 290
B. Antimetabolites . . 290
1. Folic Acid Analogs 290
Methotrexate (MTX) . 290
XII Contents
2. Pyrimidine Analogs . . 291
a) Fluorouracil (5-FU). 291
b) Cytarabine. 292
3. Purine Analogs . 293
C. Natural Products ... 293
1. Vinca Alkaloids . 293
2. Antibiotics .... 294
a) Dactinomycin. 294
b) Doxorubicin. 294
c) Bleomycin .. 295
d) Mithramycin. 297
e) Mitomycin. 297
3. Enzymes ..... 298
Asparaginase. . . 298
D. Miscellaneous Agents 298
1. Cisplatin..... 298
2. Hydroxyurea (HU) 299
3. Procarbazine. 299
4. Etoposide .. 300
E. Hormones . . . 301
1. Tamoxifen. 301
2. Steroids... 302
IV. Practical Pharmacologic Considerations 303
A. Combination Chemotherapy 303
B. Drug Resistance . . . . . . 305
C. Neurotoxicity ....... . 306
1. Peripheral Neuropathy 307
2. Myopathy . . . . . . . 309
3. Arachnoiditis/Myelopathy 309
4. Acute Encephalopathy . . 310
5. Chronic Encephalopathy . 310
6. Acute Cerebellar Syndrome. 311
7. Syndrome on Inappropriate Antidiuretic Hormone. 312
V. Histopathologic Effects of Brain Tumor Chemotherapy. 312
VI. Modes of Drug Administration . 313
A. Intraarterial Administration. 314
B. Intrathecal Administration . 316
C. Intratumoral Administration 317
D. Liposome Drug Delivery .. 318
VII. Blood-Brain Barrier Disruption (BBBD) . 319
VIII. Drug Rescue Techniques. 323
IX. Radiation Sensitizers. . . . . . . . . . 324
X. Monoclonal Antibodies . . . . . . . . 325
XI. Special Cases in CNS Tumor Therapy 325
A. Primary CNS Lymphomas . . . . 325
B. Primitive Neuroectodermal Tumors 326
C. Germ Cell Tumors. 327
D. Brain Metastases. 328
XII. Experimental Drugs 329
XIII. Drug Protocols . 332
XIV. Conclusion 334
References . . . . . . . 336