Neurological Complications of Systemic Cancer and Antineoplastic Therapy 2e Herbert B. Newton (editor), Mark G. Malkin (editor)

Neurological Complications of Systematic Cancer and Antineoplastic Therapy,A really cool book Second Edition provides an expanded, updated and in-depth review of common manifestations related to neurology that occur in patients with systemic cancer. These include brain metastases, spinal cord compression, cerebrovascular events, and leptomeningeal disease. The book also discusses neurological complications related to treatments such as radiation and chemotherapy and is an essential reference for the practicing neurologist and oncologist. Sections in this new release cover the pathophysiology and molecular biology of cancer and the metastatic phenotype, Metastatic spread to cranial and peripheral nerves and brachial and lumbosacral plexuses, Metabolic and nutritional disorders, CNS infections, Neurological complications of immunotherapy and bone marrow transplants, Neurological complications of new molecular agents and immuno-modulatory drugs, and more. Summarizes the neurologic effects of both cancer and cancer treatment Provides scientific and clinical information relevant to research and treatment Identifies neurological complications by tumor type and tumor therapy Covers GI, lung, breast, gynecological, head and neck cancers, and more Includes radiotherapy, chemotherapy, immunotherapy, and new drugs Contains melanoma, lymphoma, sarcoma, myeloma, leukemia, and more Front Cover Neurological Complications of Systemic Cancer and Antineoplastic Therapy Copyright Dedication Contents Contributors About the editors Preface Section I Metastatic neurological complications Chapter 1 Common symptoms at presentation of nervous system metastases 1 Introduction 2 Brain metastases 2.1 Headache 2.2 Seizures 2.3 Alerted mental status/neurocognitive symptoms 2.4 Focal neurologic deficits 3 Leptomeningeal disease 4 Spinal cord metastases 5 Epidural spinal cord metastases/epidural spinal cord compression 6 Cauda equina syndrome 7 Neoplastic and radiation plexopathy 8 Conclusion References Chapter 2 Neuroimaging of systemic metastatic disease 1 Technical considerations 2 Anatomic locations 2.1 Brain parenchyma 2.2 Calvarium and skull base 2.3 Dura 2.4 Leptomeningeal 2.5 Miscellaneous intracranial metastases 2.6 Spine 2.7 Malignant and treatment-induced plexopathy 3 Intracranial complications of systemic disease 3.1 Posterior reversible encephalopathy syndrome 3.2 Methotrexate-induced leukoencephalopathy 3.3 Cytarabine-induced vasospasm 3.4 Immune checkpoint inhibitor-induced hypophysitis 3.5 Progressive multifocal leukoencephalopathy 3.6 Autoimmune and paraneoplastic encephalitis 3.7 Radiation necrosis and pseudoprogression 3.8 Radiation-induced arteriopathy 3.9 Stroke-like migraine attacks after radiation therapy syndrome Acknowledgment References Chapter 3 Nonimaging evaluation of patients with nervous system metastases 1 Introduction 2 Electroencephalography 2.1 Epilepsy 2.2 Nonepileptiform changes 3 Evoked potentials 3.1 Diagnostic utility 3.2 Intraoperative utility 3.2.1 SSEPs 3.2.2 MEPs 4 Electromyography and nerve conduction studies 4.1 Spine tumors: Radiculopathy 4.2 Peripheral nerve tumors: Plexopathies and neuropathies 4.2.1 Plexopathies 4.2.2 Neuropathies 5 Nerve biopsy 6 Cerebrospinal fluid 6.1 Opening pressure 6.2 Laboratory analysis 6.2.1 Chemistries and cell counts 6.2.2 Other small molecules and proteins 6.3 Flow cytometry and cytology 6.4 Liquid biopsy 6.4.1 Circulating tumor cells 6.4.2 Nucleic acids 7 Conclusion Disclosures References Chapter 4 Biology and pathophysiology of central nervous system metastases 1 Introduction 2 Molecular biology of neoplasms 2.1 Growth factor signaling—PDGF and PDGFR 2.2 Growth factor signaling—FGF and FGFR 2.3 Growth factor signaling—IGF and IGFR 2.4 Growth factor signaling—EGF 2.5 Growth factor signaling—MAPK pathway 2.6 PI3K/PTEN/AKT signaling pathway 2.7 mTOR signaling pathway 2.8 Angiogenesis signaling pathways—VEGF 2.9 Apoptosis and other pathways 3 Mechanisms of brain metastasis 3.1 Epithelial-mesenchymal transition 3.2 SNAIL proteins 3.3 Zinc finger E-box binding (ZEB) proteins 3.4 TWIST proteins 3.5 FOX proteins 3.6 KLF proteins 3.7 Other EMT factors 4 Biological mechanisms of the metastatic cascade 5 Blood–brain barrier 6 Genetics of metastases 6.1 Suppressors of metastasis 6.2 Clinically actionable mutations in brain metastases 6.3 CDK pathway 6.4 PI3K/AKT pathway 6.5 Oxidative phosphorylation pathway 6.6 YAP1 6.7 FGFR 6.8 MMP13 6.9 SPOCK1 6.10 Caveolin-1 6.11 Other genes 7 Conclusion Disclosure References Chapter 5 Intracranial metastases 1 Introduction and epidemiology 2 Pathology 3 Clinical presentation 4 Neuroimaging 5 Surgical therapy 6 Radiation therapy 7 Chemotherapy References Further reading Chapter 6 Neurosurgical approaches to the treatment of intracranial metastases 1 Background 2 Initial approach 2.1 Presentation and tissue diagnosis 2.2 Stereotactic biopsy 2.3 Craniotomy 2.4 Tubular retractor 3 Tumor resection 3.1 En bloc 3.2 Supratotal 3.3 Piecemeal 3.4 Patients with multiple brain metastases 4 Surgical adjuncts 4.1 Fluorescence 4.2 Neuronavigation 4.3 Intraoperative imaging 4.4 Intraoperative brain mapping 5 Other neurosurgical techniques 5.1 Stereotactic radiosurgery 5.2 Laser interstitial thermal therapy 6 Management of recurrence—When to repeat resection 7 Management of CNS metastases in uncommon locations 7.1 Skull base metastases 7.2 Dural metastases 7.3 Leptomeningeal disease 8 Conclusion Disclosures References Chapter 7 Epidural metastasis and spinal cord compression 1 Introduction 2 Epidemiology 3 Pathophysiology 4 Clinical presentation 4.1 Pain 4.2 Motor dysfunction 4.3 Sensory 4.4 Dysautonomia 5 Diagnosis 5.1 Magnetic resonance imaging 5.2 Computed tomography 5.3 CT myelography 5.4 Radionucleotide bone scan 5.5 Radiography 6 Prognosis 7 Treatment 7.1 Corticosteroids 7.2 Surgery 7.3 Conventional radiotherapy 7.4 Stereotactic body radiation therapy 7.5 Systemic therapy 8 Conclusion References Chapter 8 Leptomeningeal metastasis 1 Introduction 2 Prognosis 3 Anatomy 4 Pathogenesis 5 Clinical presentation 6 Diagnostic studies/staging 6.1 CSF examination 6.2 Neuroimaging 7 Treatment 7.1 Radiation therapy 7.2 Chemotherapy and targeted therapies 7.2.1 Intra-CSF therapy 7.2.2 Methotrexate 7.2.3 Cytarabine (Ara-C) 7.2.4 ThioTEPA 7.2.5 Topotecan 7.2.6 Etoposide 7.2.7 Miscellaneous intra-CSF agents 7.3 Systemic chemotherapy and targeted agents 7.3.1 Chemotherapeutic agents 7.3.2 Molecularly targeted therapies 7.4 Hormone therapy 7.5 Immunotherapy 8 Summary References Chapter 9 Cranial nerve involvement by metastatic cancer 1 Introduction 2 Clinical presentation of cranial nerve involvement 2.1 Bony metastases 2.2 Calvarial metastases 2.3 Skull base metastases 2.4 Mandibular metastases 2.5 Orbital metastases 2.6 Facial nerve involvement 2.7 Cranial nerve involvement arising from cancer of the neck or chest 3 Typical imaging findings of cranial nerve involvement 4 Cancers of special interest 4.1 Cancers of the head and neck 4.2 Squamous cell carcinoma 4.3 Nasopharyngeal carcinoma 4.4 Adenoid cystic carcinoma 4.5 Primary cutaneous neoplasms of the head and neck region 4.6 Other solid tumors of importance 4.7 Prostate cancer 4.8 Breast cancer 4.9 Hematologic involvement 4.9.1 Lymphoma 4.9.2 Leukemia 5 Summary References Chapter 10 Cancer-related plexopathies 1 Introduction 2 Review of plexus anatomy 2.1 Cervical plexus 2.2 Brachial plexus 2.3 Lumbosacral plexus 3 Plexopathy 3.1 Cervical plexopathy 3.2 Brachial plexopathy 3.3 Lumbosacral plexopathy 4 Diagnosis of plexopathy in patients with cancer 4.1 Neurologic differential diagnosis 4.2 Oncologic differential diagnosis 4.2.1 Cancer-related plexopathy 4.2.2 Treatment-related plexopathy 5 Diagnostic studies 5.1 Imaging 5.2 Electromyography 5.3 Treatment of cancer-related plexopathy 6 Cancers of special interest 6.1 Lung cancer 6.2 Breast cancer 7 Supportive treatment of cancer-related plexopathy 8 Summary References Section II Nonmetastatic neurological complications Chapter 11 Cerebrovascular complications of malignancy 1 Epidemiology of cerebrovascular disease in malignancy 1.1 Ischemic stroke 1.2 Intracranial hemorrhage 2 Direct tumor effects and intracranial hemorrhage 3 Direct tumor effects and cerebral infarction 4 Coagulation disorders 4.1 Hemorrhagic diatheses and disseminated intravascular coagulation 4.2 Microangiopathic hemolytic anemia 4.3 Nonbacterial thrombotic endocarditis 4.4 Cerebral intravascular coagulation 5 Cancer-related infectious disease and stroke: Septic cerebral infarction 6 Infectious vasculitis 7 Complications of cancer treatment 7.1 Chemotherapy 7.2 Radiation therapy 7.3 Hematopoietic stem-cell transplantation 8 Conclusion References Chapter 12 Metabolic and nutritional nervous system dysfunction in cancer patients☆ 1 Introduction 2 Metabolic and toxic encephalopathy 2.1 Organ failure 2.2 Electrolyte abnormalities 2.3 Hypoglycemia 2.4 Hyperglycemia 2.5 Vitamin deficiency 2.6 Endocrine disorders 2.7 Septic encephalopathy 2.8 Drug reactions 2.9 Drug intoxications 3 Tumor lysis syndrome 4 Cancer anorexia-cachexia syndrome 5 Nutritional myelopathy 6 Peripheral neuropathy 7 Nutritional and toxic myopathy 8 Immunotherapy side effects 8.1 Myositis 8.2 Hepatotoxicity 8.3 Pneumonitis 8.4 Endocrinopathies 8.5 Neuropathies 8.6 Aseptic meningitis 9 CAR-T cell complications References Chapter 13 Central nervous system infections in cancer patients 1 Introduction 2 Approach to cancer patients with suspected CNS infection 2.1 Five clinical challenges 2.2 Diagnostic approach to potential CNS infection 2.2.1 Use epidemiologic clues 2.2.2 Recognize clinical syndromes on physical examination 2.2.3 Exclude noninfectious conditions mimicking CNS infection 2.2.4 Order cost-effective laboratory studies 3 High-risk patient groups 3.1 Transplant recipients (hematopoietic stem cell and solid organ) 3.1.1 Infections according to time from transplantation Early posttransplant period (0–30 days) 3.1.2 Six special situations 3.2 Neurosurgical patients 3.2.1 Recent neurosurgery group 4 Management of common CNS infections 4.1 General medical management issues 4.2 Bacterial meningitis 4.3 Endocarditis 4.4 Fungal infections 4.5 Viral infections 4.5.1 Varicella-zoster virus 4.5.2 Human herpesvirus 6 4.5.3 Progressive multifocal leukoencephalopathy 5 Vaccine-preventable infections: The COVID-19 pandemic and cancer patients 6 Conclusions References Chapter 14 Diagnosis and treatment of paraneoplastic neurological disorders 1 Introduction 2 Pathogenesis 3 Clinical diagnosis 3.1 Clinical symptoms 3.2 Cerebrospinal fluid 3.3 Radiographic assessment 3.4 Tissue sampling 4 Antineuronal antibodies 5 Treatment 5.1 Antibody-mediated to cell membrane antigens 5.2 Autoantibodies directed against intracellular neuronal proteins (cytotoxic T-cell-mediated process) 5.3 Other possible options 5.4 Additional considerations 6 Underlying malignancy 7 Paraneoplastic disorders and immune checkpoint inhibitors 8 Paraneoplastic neurological disorders 8.1 Paraneoplastic cerebellar degeneration 8.2 PEM and focal encephalitis 8.3 Paraneoplastic limbic encephalopathy 8.4 Brainstem encephalitis 8.5 Myelitis 8.6 Opsoclonus-myoclonus 8.7 Stiff-person syndrome 8.8 Lambert-Eaton myasthenic syndrome 8.9 Paraneoplastic sensory neuronopathy 8.10 Paraneoplastic neuropathies 8.11 Vasculitis of the nerve and muscle 8.12 Myasthenia gravis 8.13 Dermatomyositis 8.14 Paraneoplastic visual syndromes 9 Conclusion References Section III Neurological complications of specific neoplasms Chapter 15 Neurological complications of lung cancer 1 Introduction 1.1 Epidemiology 1.2 Tumor classification 1.3 General oncologic management 1.3.1 Nonsmall cell lung cancer Localized disease Locally advanced disease Metastatic disease Targeted therapies Immunotherapy Cytotoxic chemotherapy 1.3.2 Small cell lung cancer 2 Direct complications of lung cancer 2.1 Parenchymal brain metastases 2.1.1 Epidemiology 2.1.2 Molecular pathogenesis 2.1.3 Clinical manifestations 2.1.4 Diagnosis 2.1.5 Treatment Surgery Radiation therapy Systemic therapy Nonsmall cell lung cancer Targeted therapy Immunotherapy Cytotoxic chemotherapy Small cell lung cancer 2.1.6 Prognosis 2.2 Spinal cord metastases 2.3 Leptomeningeal metastases 2.3.1 Incidence by tumor type 2.3.2 Manifestations 2.3.3 Diagnosis Radiologic findings Lumbar puncture 2.3.4 Management Systemic therapy Targeted therapy EGFR mutations ALK rearrangement Cytotoxic chemotherapy Immunotherapy Radiation therapy Ventriculoperitoneal shunting 2.3.5 Prognosis 2.4 Dural-based metastases 2.4.1 Intracranial epidural space 2.4.2 Spinal epidural space Epidural spinal cord compression Incidence Signs and symptoms Pain Weakness Other symptoms Radiologic findings and diagnosis Mri Other imaging modalities Management Glucocorticoids Surgery Radiation therapy Chemotherapy Approach to recurrent disease Prognosis 2.5 Plexus and peripheral nerve metastases 2.5.1 Brachial plexus Manifestations Radiologic findings Diagnosis Treatment Prognosis 3 Indirect complications of lung cancer 3.1 Paraneoplastic neurologic syndromes 3.1.1 Manifestations of paraneoplastic neurologic syndromes in lung cancer patients Limbic encephalitis Paraneoplastic cerebellar degeneration Opsoclonus-myoclonus Subacute sensory neuropathy and dorsal root ganglionopathy Autonomic neuropathy Lambert-Eaton myasthenic syndrome (LEMS) Polymyositis/dermatomyositis 3.1.2 Management 3.2 Treatment-related complications 3.2.1 Immunotherapy References Chapter 16 Neurological complications of breast cancer☆ 1 Introduction 2 Metastatic complications 2.1 Skull 2.2 Dural metastasis 2.3 Leptomeningeal metastasis 2.4 Brain 2.5 Spinal epidural 2.6 Spinal cord 2.7 Optic nerve 2.8 Uvea 2.9 Pituitary 2.10 Brachial plexus 2.11 Lumbosacral plexus 3 Nonmetastatic complications 3.1 Metabolic disorders 3.2 Cerebrovascular disease 3.2.1 Disseminated intravascular coagulation 3.2.2 Thrombotic microangiopathy 3.2.3 Nonbacterial thrombotic endocarditis 3.2.4 Cerebral vein thrombosis 3.2.5 Intravascular mucin 3.2.6 Intracerebral hemorrhage 3.3 Infections 3.4 Complications of chemotherapy 3.4.1 Intrathecal chemotherapy 3.4.2 Ocular complications of tamoxifen 3.4.3 Other complications of chemotherapy 3.5 Complications of radiotherapy 3.5.1 Brachial plexus 3.6 Complications of surgery 3.6.1 Intercostobrachial neuralgia 3.6.2 Other complications of surgery 3.7 Paraneoplastic syndromes 3.7.1 Cerebellar degeneration 3.7.2 Opsoclonus-myoclonus syndrome 3.7.3 Limbic encephalitis 3.7.4 Stiff-person syndrome 3.7.5 Sensory and sensorimotor neuropathy 3.7.6 Motor neuron disease 3.7.7 Other paraneoplastic syndromes 4 Regional approach to the diagnosis of neurological symptoms 5 Conclusion References Chapter 17 Neurological complications of melanoma 1 Introduction 2 Neurological complications of malignant melanoma 2.1 Introduction 2.2 Clinical presentation 2.2.1 Incidence and clinical features 2.2.2 Brain metastases from malignant melanoma Symptoms and signs Diagnosis Therapy of brain metastases 2.2.3 Spinal metastases from metastatic melanoma 2.2.4 Leptomeningeal metastases from metastatic melanoma 2.2.5 Peripheral nerve complications 2.2.6 Survival and cause of death 2.2.7 l -dopa therapy and malignant melanoma 2.2.8 Paraneoplastic syndromes 3 Neurological complications of noncutaneous melanomas 3.1 Primary nervous system melanoma 3.2 Metastatic ocular melanoma References Chapter 18 Neurological complications of lymphoma 1 Introduction 1.1 Central nervous system prophylaxis 2 Intracranial metastases 2.1 Parenchymal disease 2.2 Meningitic disease: Leptomeningeal metastases 2.3 Intravascular lymphomatosis 3 Spinal cord processes 3.1 Intramedullary spinal cord metastases 3.2 Epidural lymphoma 4 Peripheral nervous system disease 4.1 Neurolymphomatosis 4.2 Cranial neuropathies 4.3 Nerve root disease, plexopathies, and other peripheral neuropathies 5 Paraneoplastic neurological syndromes 5.1 Cerebellar degeneration 5.2 Limbic encephalitis 5.3 Neuromuscular junction syndromes 5.3.1 Lambert-Eaton and myasthenic syndrome 5.4 Dermatomyositis and polymyositis References Chapter 19 Neurologic complications of the leukemias 1 Introduction 2 Diagnostic considerations 3 The acute leukemias 3.1 Acute lymphocytic leukemia 3.2 Acute myeloid leukemia 4 The chronic leukemias 4.1 Chronic lymphocytic leukemia 4.2 Chronic myelogenous leukemia 5 Conclusion References Chapter 20 Neurological complications of systemic cancer of the head and neck 1 Introduction 2 Local and locoregional complications 2.1 Local growth 2.2 Lymphatic spread 2.3 Perineural spread 3 Distant metastases 3.1 Cerebral metastases 3.2 Spinal metastases 4 Leptomeningeal carcinomatosis 4.1 The nonmetastatic complications 4.2 Metabolic complications 4.2.1 Wernicke encephalopathy 4.3 Paraneoplastic syndromes 4.4 Complications associated with treatment 4.4.1 Surgery 4.4.2 Treatment/exercises 4.4.3 Radiotherapy-linked complications 4.4.4 Dysphagia 5 Medical therapy 5.1 Cisplatin 5.2 Carboplatin 5.3 Paclitaxel and docetaxel 5.4 Fluorouracil (5-FU) 5.5 Immunotherapy 6 Syncope in patients with head and neck cancer References Further reading Chapter 21 Neurological complications of gynecological cancers 1 Introduction 2 Local/regional spread of gynecological cancers to the lumbosacral plexus 3 Distant CNS metastases from gynecological cancers 3.1 Spine metastases from gynecological cancers: Symptoms, testing, treatment 3.2 Brain metastases: Symptoms, testing, treatment 3.3 Calvarial, dural, and leptomeningeal metastases: Symptoms, testing, treatment 4 Paraneoplastic syndromes due to gynecological cancers 5 Neurological complications associated with treatment of gynecological cancers 5.1 Complications of gynecological cancer surgery 5.2 Neurological complications of gynecological radiation therapy 5.3 Neurological complications of gynecological cancer systemic therapy 6 Conclusion References Chapter 22 Neurological complications of GI cancers 1 Overview of gastrointestinal cancers 1.1 Esophageal cancer 1.2 Gastric cancer 1.3 Hepatocellular cancer 1.4 Gallbladder and biliary tract cancer 1.5 Pancreatic cancer 1.6 Colorectal cancer 1.6.1 Genetic syndromes of colorectal and CNS neoplasms 1.7 Neuroendocrine tumors (carcinoid tumors) 2 Neurological complications of GI cancers 2.1 Brain metastasis 2.1.1 Brain metastasis from esophageal cancer 2.1.2 Brain metastasis from gastric cancer 2.1.3 Brain metastasis from hepatocellular cancer 2.1.4 Brain metastasis from gallbladder and biliary tract cancer 2.1.5 Brain metastasis from pancreatic cancer 2.1.6 Brain metastasis from colorectal cancer 2.2 Leptomeningeal metastasis 2.2.1 Leptomeningeal metastasis from esophageal cancer 2.2.2 Leptomeningeal metastasis from gastric cancer 2.2.3 Leptomeningeal metastasis from other GI cancers 2.3 Spinal cord compression 2.4 Plexopathy 2.5 Paraneoplastic neurological syndromes 2.5.1 PNS from esophageal cancer 2.5.2 PNS from gastric cancer 2.5.3 PNS from hepatocellular carcinoma 2.5.4 PNS from cancers of the gallbladder and biliary tract 2.5.5 PNS from pancreatic cancer 2.5.6 PNS from colorectal cancer 2.6 Metabolic and cerebrovascular complications 2.7 Pain management 3 Common systemic treatment regimens for GI cancers and their neurological complications 3.1 Chemotherapy 3.1.1 Fluoropyrimidines 3.1.2 Platinum 3.1.3 Taxanes 3.1.4 Gemcitabine 3.1.5 Irinotecan 3.1.6 Trifluridine/tipiracil 3.2 Targeted therapy 3.2.1 Vascular endothelial growth factor (VEGF) inhibitor 3.2.2 Human epidermal growth receptor 2 (HER2/neu) inhibitor 3.2.3 Multitarget tyrosine kinase inhibitor (TKI) 3.2.4 Epidermal growth factor receptor (EGFR) kinase inhibitor 3.2.5 BRAF inhibitor 3.2.6 Fibroblast growth factor receptor (FGFR) kinase inhibitor 3.2.7 Isocitrate dehydrogenase 1 (IDH 1) inhibitor 3.2.8 Neurotrophic tropomyosin-related kinase (NTRK) inhibitor 3.3 Immunotherapy 3.3.1 Immune checkpoint (ICP) inhibitors Permissions summary References Chapter 23 Neurologic complications associated with genitourinary cancer 1 Introduction 2 Prostate cancer 2.1 Epidural spinal cord compression 2.2 Brain metastases 2.3 Base of the skull metastases 2.4 Paraneoplastic syndromes 2.5 Treatment-related complications 3 Uterus 3.1 Uterine cervix 3.2 Uterine body 4 Ovarian cancer 4.1 Brain metastases 4.2 Leptomeningeal metastases 4.3 Paraneoplastic syndromes 4.4 Treatment-related complications 5 Renal carcinoma 5.1 Brain metastases 5.2 Epidural spinal cord compression 5.3 Paraneoplastic syndromes and leptomeningeal metastases 5.4 Treatment-related complications 6 Germ cell testicular cancer 6.1 Brain metastases 6.2 Epidural spinal cord compression 6.3 Paraneoplastic syndromes 6.4 Treatment-related complications 7 Bladder carcinoma 7.1 Brain metastases 7.2 Leptomeningeal metastases 7.3 Spinal cord complications 7.4 Lumbosacral plexopathy 7.5 Paraneoplastic syndromes 8 Conclusion References Chapter 24 Sarcoma and the nervous system 1 Introduction 2 Primary CNS sarcomas 2.1 DICER1-associated central nervous system sarcoma 2.2 Solitary fibrous tumor of the nervous system/hemangiopericytoma 2.3 Primary CNS histiocytic sarcoma 2.4 Kaposi’s sarcoma 2.5 Ewing’s sarcoma 2.6 Leiomyosarcoma 2.7 Angiosarcoma 2.8 Radiation-induced sarcomas affecting the CNS 3 Primary sarcomas of the peripheral nervous system 3.1 Malignant peripheral nerve sheath tumors 4 Extra-CNS sarcoma affecting the nervous system 4.1 Chordoma 4.2 Chondrosarcoma 4.3 Osteosarcoma 5 CNS metastases from extra-CNS sarcoma 6 Neurologic toxicities from sarcoma treatments 6.1 Peripheral neuropathy 6.2 Hearing loss 6.3 Central nervous system complications 7 Conclusions References Chapter 25 Neurological complications of multiple myeloma 1 Introduction 2 Central nervous system complications 2.1 Spinal cord compression 2.2 Central nervous system myelomatosis 2.3 Hyperviscosity syndrome 2.4 Toxic metabolic encephalopathy 2.4.1 Uremia 2.4.2 Hypercalcemia 3 Peripheral nervous system complications 3.1 Compression, infiltration, and numb chin syndrome 3.2 Multiple myeloma-associated peripheral neuropathy 3.3 Treatment-emergent peripheral neuropathy 3.3.1 Proteasome inhibitors 3.3.2 Thalidomide 3.4 Other plasma cell dyscrasias 3.4.1 Amyloidosis 3.4.2 POEMS syndrome 3.4.3 Waldenström’s macroglobulinemia 4 Conclusion References Chapter 26 Neurologic complications in the treatment of childhood malignancies 1 Introduction 2 Part I: Acute complications of cancer treatment 2.1 Systemic chemotherapy 2.1.1 Seizures 2.1.2 Stroke 2.1.3 Encephalopathy 2.1.4 Posterior reversible encephalopathy syndrome (PRES) 2.1.5 Peripheral neuropathy 2.1.6 Ototoxicity 2.2 Radiation therapy 2.2.1 Early effects (< 1 month)—Encephalopathy 2.2.2 Subacute effects (1–6 months)—Postradiation somnolence syndrome 2.3 Hematopoietic stem cell transplantation 2.3.1 Acute effects (< 6 months) 2.4 Novel agents: Immune-based therapies 2.4.1 T-cell-based immunotherapy 2.4.2 Immune checkpoint inhibitors 2.4.3 Vaccines 2.4.4 Viral therapies 3 Part II: Late effects of cancer treatment 3.1 Systemic chemotherapy 3.1.1 Neurocognitive sequelae 3.1.2 Chemotherapy-induced peripheral neuropathy (CIPN) 3.1.3 Ototoxicity 3.2 Radiation therapy 3.2.1 Neurocognitive defects 3.2.2 Cardiovascular injury: Stroke, moyamoya 3.2.3 SMART syndrome 3.2.4 Vascular malformations: Cavernous malformation, aneurysms 3.2.5 Endocrinopathies Growth hormone deficiency Gonadotrophin deficiency Adrenocorticotropic hormone deficiencies Hypothyroidism Obesity 3.2.6 Secondary malignancy 3.3 Hematopoietic stem cell transplant 3.4 Novel agents: Immune-based therapies 4 Conclusion References Section IV Neurological complications of antineoplastic therapy Chapter 27 Neurological complications of radiation therapy 1 Introduction 2 Pathophysiology of neurological complications from radiation 3 Radiation-induced brain toxicity 3.1 Acute complications 3.2 Early-delayed complications 3.3 Late-delayed complications 4 Radiation-induced complications of spinal cord 4.1 Acute and early-delayed myelopathy 4.2 Late-delayed myelopathy 5 Radiation-induced nerve injury 5.1 Toxicity of cranial nerves after radiation 5.2 Radiation-induced brachial plexopathy 5.3 Radiation-induced lumbosacral plexopathy 6 Endocrinopathy after radiation therapy 7 Cerebrovascular complications after radiation treatment 8 Radiation-induced secondary malignancy 9 Conclusion References Chapter 28 Neurological complications of systemic cancer and antineoplastic therapy 1 Introduction 2 Mechanisms of neurotoxicity 3 Neurotixicity of specific agents 3.1 Alkylating agents 3.1.1 Nitrosoureas 3.1.2 Busulfan 3.1.3 Chlorambucil 3.1.4 Cyclophosphamide 3.1.5 Ifosfamide 3.1.6 Procarbazine 3.1.7 Temozolomide 3.1.8 Thiotepa 3.1.9 Other alkylating agents 3.2 Antimetabolites 3.2.1 2-Chlorodeoxyadenosine (cladribine) 3.2.2 Capecitabine 3.2.3 Cytosine arabinoside (Cytarabine, Ara-C) 3.2.4 Fludarabine 3.2.5 5-Fluorouracil (5-FU) 3.2.6 Gemcitabine 3.2.7 Hydroxyurea 3.2.8 Methotrexate 3.2.9 Pentostatin 3.3 Platinum compounds 3.3.1 Cisplatin 3.3.2 Carboplatin 3.3.3 Oxaliplatin 3.4 Antineoplastic antibiotics 3.5 Vinca alkaloids 3.6 Taxanes 3.6.1 Paclitaxel 3.6.2 Docetaxel 3.7 Topoisomerase inhibitors 3.7.1 Topotecan 3.7.2 Etoposide and teniposide 4 Targeted therapies 4.1 Monoclonal antibodies 4.1.1 Bevacizumab 4.1.2 Cetuximab 4.1.3 Iodine-131 tositumomab 4.1.4 Rituximab 4.1.5 Trastuzumab (Herceptin) 4.1.6 Brentuximab vedotin 4.1.7 Polatuzumab vedotin 4.1.8 Other monoclonal antibodies 4.2 Small-molecule tyrosine kinase inhibitors 4.2.1 BCR-Abl inhibitors 4.2.2 Epidermal growth factor receptor inhibitors 4.2.3 Vascular endothelial growth factor receptor (VEGFR) inhibitors 4.2.4 Anaplastic lymphoma kinase (ALK) inhibitors 4.2.5 Proteasome inhibitors 4.2.6 Neurotrophic tyrosine receptor kinase (NTRK) inhibitors 4.2.7 Other tyrosine kinase (TKI) inhibitors 5 Biological agents 5.1 Immune modulators 6 Chemotherapy-induced cognitive impairment 7 Conclusion References Chapter 29 Neurological complications of hematopoietic stem cell transplantation 1 Introduction 2 Neurologic complications associated with conditioning regimens 2.1 Alemtuzumab 2.2 Antithymocyte globulin (ATG) 2.3 Busulfan 2.4 Cyclophosphamide 2.5 Cytosine arabinoside 2.6 Fludarabine 2.7 Melphalan 2.8 Thiotepa 2.9 Total body irradiation (TBI) 3 Toxic-metabolic encephalopathy 4 Cerebrovascular complications 4.1 Intracranial hemorrhage (ICH) 4.2 Ischemic strokes 4.3 Transplant-associated thrombotic microangiopathy (TA-TMA) 5 CNS infections 5.1 Fungal 5.2 Parasitic 5.3 Viral 5.4 Bacterial 6 Neurologic complications associated with chronic graft versus host disease (GVHD) 7 Neurologic complications associated with immunosuppressive therapy 7.1 Corticosteroids 7.2 Calcineurin inhibitors 8 Neurocognitive dysfunction 9 Secondary malignancies 10 Conclusion References Chapter 30 Chemotherapy-induced peripheral neuropathy 1 Introduction 2 Pathophysiology of CIPN 3 Clinical presentation and diagnostic evaluation of CIPN 4 Clinical management of CIPN References Chapter 31 Neurological complications of immunotherapy and monoclonal antibody therapy 1 Introduction 2 Bevacizumab 2.1 Bevacizumab and cerebrovascular events 2.2 Bevacizumab and RPLS 2.3 Bevacizumab and optic neuropathy 3 Cetuximab and other anti-EGFR mAbs 3.1 Cetuximab and aseptic meningitis 3.2 Cetuximab and hypomagnesemia 3.3 Cetuximab and RPLS 3.4 Other anti-EGFR mAbs 4 Trastuzumab 5 Rituximab and other anti-CD20 mAbs 5.1 Rituximab and PML 5.2 Rituximab and RPLS 5.3 Other anti-CD20 mAbs 6 Dinutuximab 7 Brentuximab vedotin 7.1 Brentuximab vedotin and peripheral neuropathy 7.2 Brentuximab vedotin and PML 8 Polatuzumab vedotin 9 Enfortumab vedotin 10 Trastuzumab emtansine 11 Blinatumomab 12 Interleukin-2 (IL2) 12.1 IL2 and acute/subacute encephalopathy 12.2 IL2 and peripheral neuropathies 13 Interferon alpha 13.1 Interferon alpha and subacute encephalopathy 13.2 Interferon alpha and chronic neuropsychiatric manifestations 13.3 Interferon alpha and peripheral neurotoxicities References Chapter 32 Neurologic complications of immune modulatory therapy 1 Introduction 2 Epidemiology 2.1 Neurologic immune-related adverse events from immune checkpoint blockade therapy 2.2 Neurotoxicity from chimeric antigen-receptor T cell therapy (ICANS) 3 Headache 4 Malignant cerebral edema 5 Peripheral nervous system 5.1 Neuropathy 5.1.1 Subacute to chronic onset: Cranial neuropathy; sensory and motor neuropathy resembling chronic inflammatory demyeli ... 5.1.2 Autonomic neuropathy 5.1.3 Mononeuritis multiplex 5.1.4 Guillain-Barré syndrome—Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 5.2 Myasthenia gravis and myositis 6 Central nervous system 6.1 Hypophysitis 6.2 Aseptic meningitis 6.3 Encephalitis, demyelination syndromes, and cerebellitis 7 CAR T cell-mediated neurotoxicity (immune effector cell-associated neurotoxicity syndrome) 8 Conclusion: Diverse presentation, kinetics, importance of multidisciplinary and early treatment, consideration of re-ch ... References Chapter 33 Neurological complications of steroids and of supportive care 1 Introduction 2 Corticosteroids 2.1 Steroid-induced myopathy 2.2 Epidural lipomatosis 2.3 Cognitive impairment 2.4 Major psychiatric disturbance 2.5 Minor neuropsychiatric symptoms 2.6 Steroid dosing 3 Seizures 3.1 Side effects of antiepileptic drugs 3.2 Drug interactions with AEDs 4 Vascular complications 5 Analgesics 5.1 Opioids 5.2 Nonsteroidal antiinflammatory drugs 5.3 Antiepileptic drugs and antidepressants 6 Antiemetics 7 Depression 8 Summary Acknowledgment References Section V Psychiatric, pain, psychosocial, and supportive care issues Chapter 34 Psychiatric aspects of care in the cancer patient 1 Introduction 2 Historical background 3 Common psychological responses to cancer 4 Epidemiology of psychiatric disorders in cancer patients 5 General principles of psychiatric assessment and treatment in patients with cancer 6 Delirium 7 Adjustment disorders 8 Anxiety disorders 9 Trauma and stressor-related disorders 10 Depressive disorders 10.1 Table for diagnostic criteria 11 Suicide assessment and management in cancer patients 12 Psychiatric considerations in cancer-related fatigue 13 Cancer survivors 14 Families issues and bereavement 15 Psychological issues for staff References Chapter 35 Chronic cancer pain syndromes and their treatment 1 Bone pain 1.1 Differential diagnosis 1.2 Multifocal or generalized bone pain 1.3 Vertebral syndromes 1.4 Back pain and epidural compression (see Chapter 7—Spinal Cord Compression) 1.5 Pain syndromes of the bony pelvis and hip 1.6 Arthritidis 1.6.1 Hypertrophic pulmonary osteoarthropathy 2 Pain syndromes of the viscera and miscellaneous tumor-related syndromes 2.1 Hepatic distention syndrome 2.2 Midline retroperitoneal syndrome 2.3 Intestinal obstruction 2.4 Peritoneal carcinomatosis 2.5 Malignant perineal pain 2.6 Adrenal pain syndrome 2.7 Ureteric obstruction 2.8 Ovarian cancer pain 2.9 Lung cancer pain 2.10 Other uncommon visceral pain syndromes 3 Headache and facial pain 3.1 Ear and eye pain syndromes 3.2 Uncommon causes of headache and facial pain 4 Neuropathic pain involving the peripheral nervous system 4.1 Painful radiculopathy 4.2 Plexopathies 5 Paraneoplastic nociceptive pain syndromes 6 Chronic pain syndromes associated with cancer thera