Therapy of Malignant Brain Tumors, 1987

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.

1 Pathology of Human Intracranial Neoplasia.- I. Introduction.- II. Basic Principles of Neurooncology.- 1. General Biology of Brain Tumors.- 2. Microvasculature and Blood-Brain Barrier (BBB).- 3. Immunological Responses.- III. Classification and Grading.- IV. Epidemiology.- V. Special Neurooncology.- 1. Tumors of Neuroepithelial Tissue.- A. Glial Tumors or Gliomas.- 1. Astrocytic Tumors.- 2. Oligodendroglial Tumors.- 3. Ependymal Tumors.- 4. Mixed Gliomas.- 5. Glioblastomatous Tumors.- 6. Choroid Plexus Tumors.- B. Pineal Cell Tumors.- C. Neuronal Tumors.- D. Embryonal Tumors.- 1. “Primitive” Neuroectodermal Tumors NOS.- 2. PNET with Differentiation.- 3. Medulloblastoma, NOS, and with Differentiation.- 2. Tumors of Nerve Sheath (Nerve Sheath Cells).- A. Neurilemmoma.- B. Neurofibroma.- C. Anaplastic Nerve Sheath Tumors.- 3. Tumors of Meningeal and Related (Mesenchymal) Tissues.- A. Meningiomas.- 1. Meningioma NOS.- 2. “Papillary” Meningioma.- 3. Anaplastic Meningioma.- 4. Meningio-Angiomatosis.- B. Primary Melanocytic Tumors.- C. Meningeal Sarcomatous Tumors.- 1. Meningeal Sarcoma and Primary Meningeal Sarcomatosis.- 2. Fibrosarcoma.- 3. Sarcoma with Glio(blastomatous) Component (“Sarcoglioma”).- 4. Rhabdomyosarcoma and Leiomyosarcoma.- 5. Mesenchymal Chondrosarcoma.- 6. Xanthosarcoma.- 4. Primary Malignant Lymphomas.- 5. Tumors of Blood Vessel Origin.- A. Hemangioblastoma.- B. Hemangiopericytoma.- C. Neoplastic “Angioendotheliosis (Angioendotheliomatosis)”—Intravascular Lymphomatosis.- 6. Germ Cell Tumors.- A. Germinoma.- B. Embryonal Carcinomas.- C. Choriocarcinoma and Endodermal Sinus Tumor.- D. Teratomas.- 7. Malformative Tumors.- A. Craniopharyngioma.- B. Rathke Cleft Cyst.- C. Epidermoid and Dermoid Cyst.- D. Colloid Cysts of the Third Ventricle (Paraphyseal) or Neuroepithelial Cyst.- E. Enterogenous and Respiratory Cyst.- F. Other Cysts.- G. Lipoma.- H. Granular Cell Tumors (Choristoma).- I. Hamartomas.- 1. Hypothalamic Neuronal Hamartoma.- 2. Glial Hamartoma.- 3. Meningioangioneurinomatosis.- 8. Tumors of Neuroendocrine Origin.- A. Pituitary Tumors.- 1. Pituitary Adenomas.- 2. Pituitary Carcinoma.- 9. Local Extension from Regional Tumors.- A. Chemodectoma (Paraganglioma).- B. Chordoma.- C. Chondroma, Osteochondroma, Chondrosarcoma.- D. Olfactory Neuroblastoma (Esthesioneuroblastoma).- 10. Metastatic Tumors.- 11. Unclassified Tumors.- References.- 2 Neurosurgery of Malignant Brain Tumors.- I. Introduction and Historical Retrospect.- II. General Neurosurgery.- a) Diagnosis by Means of Noninvasive and Invasive Measures.- 1. Methods for Measurements of Intracranial Pressure.- 2. Ventriculography with Positive Contrast Medium.- 3. CT-controlled Stereotactic Tumor Biopsy.- b) Preoperative and Postoperative Monitoring.- c) Associated Perioperative Procedures and Palliative Operations.- 1. Ventriculo-atrial Drainage.- 2. Ventriculo-peritoneal Drainage.- 3. Ventriculo-cisternal Drainage (Interventriculostomy).- 4. Ventriculo-cisternal Drainage.- 5. Implantation of an Ommaya Reservoir.- 6. Preliminary Ventricular Drainage.- 7. Perioperative Administration of Antibiotics.- d) General Operative Technique.- e) Special Technical Aids.- 1. The Operating Microscope.- 2. Use of the Laser in Neurosurgery.- 3. Electrocoagulation.- 4. The Use of Ultrasound.- 5. Microsurgical Instruments and Suture Material.- III. Special Neurosurgery.- a) Tumors of the Supratentorial Space.- Tumors of the Cerebral Hemisphere.- Intraventricular Lesions.- Midline Intrinsic Brain Tumors.- b) Tumors of the Posterior Fossa.- IV. Significance of the Surgical Measures and Critical Assessment of Their Results.- References.- 3 Neurosurgical Interventions for Intracranial Metastases.- Data on the Morbidity.- Indications for Operation.- Operative Technique.- Results of Operation.- References.- 4 Stereotactic Biopsy and Technique of Implantation (Instillation) of Radionuclids.- 1. Biopsy for Differentiation of Intracranial Processes and Optimization of Therapy.- a) Technique of CT (MRI) Stereotaxy for Biopsy and Implantation of Radioisotopes.- b) Technique of Biopsy.- c) Clinical Results of Biopsy.- d) Consecutive Procedures After Biopsy.- 2. Curie (Brachy-Curie) Therapy (BCiT).- a) Radiobiology of the Low-Dose Rate CiT.- b) Radiobiology of High-Dose Rate Brachy-Curie Therapy (BCiT).- 3. Techniques of Implantation of Radionuclides.- a) Curie Therapy.- b) Technique of Brachy-Curie Therapie (BCiT).- c) Contact Radiation Devices.- 4. Results of BCiT.- 5. New Results of BCiT.- 6. The Place of BCiT in the Treatment Plan.- 7. Indications for Curie (Brachy-Curie) Therapy and Combined Radiotherapy.- References.- 5 Radiation Therapy of Brain Tumors.- 1. Introduction.- 2. Fundamentals of Radiotherapy.- 2.1 Radiation Sensitivity and Radioresistance.- 2.2 Types of Radiation.- 2.3 Radiation Dose.- 2.3.1 Definitions.- 2.3.2 The Effect of the Dose on Tumor Control.- 2.4 Treatment Volume.- 2.4.1 Glioblastoma Multiforme.- 2.4.2 Medulloblastoma.- 2.4.3 Ependymoma.- 2.4.4 Pineal Tumors and Suprasellar Germinomas.- 2.5 Dose per Fraction.- 2.5.1 Hyperfractionation.- 2.5.2 Accelerated Fractionation.- 2.5.3 Acceleration by Hyperfractionation.- 2.6 Chemical Radiosensitizers.- 2.7 Hypoxic Cell Radiosensitizers.- 2.8 Heavy Particle Beam Irradiation.- 2.9 Hyperthermia.- 2.10 Brachytherapa (Permanent and Removable Radioactive Implants).- 2.11 Focal Radiosurgery.- 3. Radiotherapeutic Technique.- 3.1 Radiation Treatment Planning.- 3.1.1 Typing and Grading.- 3.1.2 Tumor Volume.- 3.1.3 Target Volume.- 3.1.4 Dosimetry.- 3.1.5 Simulation and Localization of the Treatment Portals.- 3.2 Technical Setting Devices.- 3.3 Interstitial Brachytherapy Technique.- 3.3.1 Erlangen Implantation Technique.- 3.3.2 Temporary Implantation.- 3.3.3 Permanent Implantation.- 4. Special Radiotherapy of Brain Tumors.- 4.1 Low-Grade Astrocytomas.- 4.2 High-Grade Astrocytomas (Glioblastomas).- 4.3 Oligodendrogliomas.- 4.4 Unbiopsied Tumors (Deep-seated Unverified Tumors).- 4.5 Tumors of the Brain Stem.- 4.6 Pineal Tumors and Suprasellar Germinomas.- 4.7 Cerebral and Cerebellar Astrocytomas in Children.- 4.8 Medulloblastoma.- 4.9 Ependymoma.- 4.10 Pituitary Adenomas.- 4.10.1 GH-secreting Adenomas (Acromegaly).- 4.10.2 ACTH-secreting Adenomas (Cushing’s Syndrome).- 4.10.3 Nelson’s Syndrome (NS).- 4.10.4 Prolactin-secreting Adenomas (Prolactinomas).- 4.10.5 Hormonally Inactive Adenomas and Giant Adenomas.- 4.11 Craniopharyngioma.- 4.12 Optic Gliomas.- 4.13 Meningiomas.- 4.14 Brain Metastases.- 5. Complications of Radiotherapy.- 5.1 Definition.- 5.1.1 Acute Reaction.- 5.1.2 Early Delayed Reaction.- 5.1.3 Late Reaction.- 5.2 Incidence of Radiation Injuries.- 5.3 Symptomatology.- 5.3.1 Acute Reaction.- 5.3.2 Early Delayed Reaction.- 5.3.3 Late Delayed Reaction.- 5.3.3.1 Brain.- 5.3.3.2 Spinal Cord.- 5.4 Radiation Tolerance of the Central Nervous System.- 5.4.1 Radiation Dose.- 5.4.1.1 Brain.- 5.4.1.2 Spinal Cord.- 5.4.2 Radiation Volume.- 5.4.3 Interaction with Chemotherapeutics.- 5.5 Conclusions.- References.- 6 Principles of Chemotherapy in Brain Neoplasia.- I. Introduction.- II. Basic Principles.- A. Cell Cycle.- B. Tumor Cell Kinetics.- C. Anatomic Considerations.- D. Prognostic Factors in Brain Tumors.- E. Cancer Pharmacokinetics.- F. Chemotherapeutic Principles.- G. Drug Classifications.- III. Specific Therapeutic Agents.- A. Alkylating Agents.- 1. Nitrogen Mustards.- a) Cyclophosphamide.- b) Mechlorethamine.- c) Melphalan.- d) Chlorambucil.- 2. Dacarbazine.- 3. Nitrosoureas.- 4. Streptozotocin.- 5. Thiotepa.- B. Antimetabolites.- 1. Folic Acid Analogs.- Methotrexate (MTX).- 2. Pyrimidine Analogs.- a) Fluorouracil (5-FU).- b) Cytarabine.- 3. Purine Analogs.- C. Natural Products.- 1. Vinca Alkaloids.- 2. Antibiotics.- a) Dactinomycin.- b) Doxorubicin.- c) Bleomycin.- d) Mithramycin.- e) Mitomycin.- 3. Enzymes.- Asparaginase.- D. Miscellaneous Agents.- 1. Cisplatin.- 2. Hydroxyurea (HU).- 3. Procarbazine.- 4. Etoposide.- E. Hormones.- 1. Tamoxifen.- 2. Steroids.- IV. Practical Pharmacologic Considerations.- A. Combination Chemotherapy.- B. Drug Resistance.- C. Neurotoxicity.- 1. Peripheral Neuropathy.- 2. Myopathy.- 3. Arachnoiditis/Myelopathy.- 4. Acute Encephalopathy.- 5. Chronic Encephalopathy.- 6. Acute Cerebellar Syndrome.- 7. Syndrome on Inappropriate Antidiuretic Hormone.- V. Histopathologic Effects of Brain Tumor Chemotherapy.- VI. Modes of Drug Administration.- A. Intraarterial Administration.- B. Intrathecal Administration.- C. Intratumoral Administration.- D. Liposome Drug Delivery.- VII. Blood-Brain Barrier Disruption (BBBD).- VIII. Drug Rescue Techniques.- IX. Radiation Sensitizers.- X. Monoclonal Antibodies.- XI. Special Cases in CNS Tumor Therapy.- A. Primary CNS Lymphomas.- B. Primitive Neuroectodermal Tumors.- C. Germ Cell Tumors.- D. Brain Metastases.- XII. Experimental Drugs.- XIII. Drug Protocols.- XIV. Conclusion.- References.- 7 Results of Chemotherapy of Malignant Brain Tumors in Adults.- 1. Diagnostics.- 1.1 Clinical Findings.- 1.2 Laboratory Findings.- 1.3 Cerebrospinal Fluid.- 1.4 EEG.- 1.5 Radioisotopic Brain Scan.- 1.6 Positron-Emission Tomography (PET).- 1.7 Angiography.- 1.8 Computer-assisted Tomography (CT).- 1.9 Nuclear Magnetic Resonance Imaging (MRI).- 1.10 Biopsy.- 1.11 Follow-up Examinations.- 1.12 Neurotoxicity.- 1.13 Neuropathological Classification.- 2. Results and Indications of Chemotherapy.- 2.1 Preliminary Remarks.- 2.2 Malignant Gliomas.- 2.2.1 Phase III Trials.- 2.2.2 Prognostic Factors.- 2.2.3 Phase II Studies in Malignant Gliomas.- 2.3 Malignant Ependymomas (WHO Grades III and IV).- 2.4 Primary Cerebral Malignant Lymphomas.- 2.5 Medulloblastomas in Adults.- 2.6 Pinealoblastomas.- 2.7 Germ Cell Tumors.- 2.8 Brain Metastases.- 2.9 Leptomeningeal Cancer, Neoplastic Meningiosis.- 3. Summary and Conclusions.- References.- 8 Malignant Brain Tumors in Children.- Clinical Features.- Symptoms and Signs of Supratentorial Tumors.- I. Cerebral Hemispheres and Lateral Ventricles.- II. Basal Ganglia and Thalamus.- III. Tumors of the Third Ventricle, (Anterior) Hypothalamus and Visual Pathways.- IV. Tumors of the Pineal Area, the Posterior Part of the Third Ventricle and Quadrigeminal Plate.- V. Tumors of the Suprasellar Region and Sella turcica.- Symptoms and Signs of Infratentorial Tumors.- VI. Tumors of the Caudal Brain Stem.- VII. Tumors of the Fourth Ventricle and the Cerebellum.- Diagnostic Tests.- Neuroradiological Investigations.- Principles of Pediatric Neurooncology.- Evaluation of Therapeutic Results.- The Blood-Brain Barrier (BBB).- Iatrogenic BBB Disruption.- Treatment of Brain Tumors by Interferon.- Cytostatic Drugs.- Side-Effects of Combined Therapy.- 1. Radiotherapy.- 2. Chemotherapy.- 3. Side-Effects of Combined Treatment.- Special Pediatric Neurooncology.- I. Astrocytoma (ASCY).- II. Glioblastoma multiforme (GLB).- III. Oligodendroglioma (OLD).- IV. Ependymoma (EPDY).- 1. Supratentorial Ependymomas.- 2. Infratentorial Ependymomas.- V. Tumors of the Pineal Region.- Clinical Remarks on Tumors of the Pineal Region.- 1. Germ Cell Tumors.- 2. Tumors Derived from Pineal Parenchyma.- Treatment of Tumors of the Pineal Region.- Results of Combined Treatment.- VI. Primitive Neuro-ectodermal Tumors (PNETs).- VII. Medulloblastoma (MBL).- Diagnostic Procedures.- Treatment.- Course.- Prognosis.- Quality of Survival.- Medical Surveillance.- VIII Miscellaneous Tumors.- IX. Tumors of the Neonatal Period and of Infancy.- Symptoms and Signs of Tumors in the First Two Years of Life.- Treatment of Infantile Brain Tumors.- References.