Biological and Clinical Landscape of Meningiomas (Advances in Experimental Medicine and Biology, 1416)

"Meningiomas are tumors that originate from the arachnoidal cap cells of the leptomeninges. With an incidence rate of 8.36 per 100, 000 population, they are the most common primary central nervous system (CNS) tumors, accounting for a third of all cases. The World Health Organization (WHO) classification has traditionally categorized meningiomas into 15 different histopathological subtypes and three clinical grades. Tumors are classified as WHO grades 1, 2 or 3 based largely on histopathological features such as mitotic activity, presence of brain invasion, and other atypical features. However, there is increasing recognition of the limitations of histopathology including but not limited to: confounding factors such as sampling bias in a heterogeneous tumor, and technical factors related to the experience of the grading pathologist. Even with careful histologic grading, there remains significant variability in recurrence rates within each tumor grade. As more studies have uncovered the molecular features of meningiomas, novel biological alterations have helped refine classification schemes that more accurately reflect patient outcomes. This book reviews the current state of knowledge on the genomic and epigenomic landscape of meningiomas in order to identify the roles of genomic aberrations on diagnosis, prognosis, and treatment of meningiomas in addition to mainstays of surgical management, radiation therapy, and potential novel chemotherapies. Written by a team of world-renowned experts in neurosurgery, neuropathology, radiology, and radiation-oncology, this book is the definitive resource on meningioma management and investigation for both clinicians and scientists alike." Foreword Acknowledgments Contents About the Contributors Paradigm Shift in the Treatment of Meningiomas 1 Treatment Timeline 2 Epidemiology 3 Treatment 4 Histology, Grading, and Molecular Biology 5 Status Quo References Clinical Presentation and Prognosis 1 Clinical Presentation 1.1 General Symptoms Epilepsy/Seizures Headache and Raised Intracranial Pressure Cognitive Function and Psychiatric Manifestations 1.2 Focal Symptoms Cranial Nerve Deficits Cortical Compression Syndromes 1.3 Incidental Meningiomas 2 Prognosis 2.1 Histological Grade 2.2 Extent of Resection 2.3 Anatomical Location Skull Base Tumors Venous Sinus Invasion 2.4 Molecular Factors and Prognosis NF2 TRAF7, AKT1, and KLF4 Smoothened PI3KCA POLR2 TERT FOXM1 2.5 Epigenetic Changes: Methylation-Based Classification 3 Conclusions and Future Directions References Imaging Characteristics of Meningiomas 1 Imaging Findings in Meningioma on Anatomical CT and MRI 2 Alternative Imaging Methods 3 Advanced MRI 4 Most Relevant Clinical Applications for Advanced MRI 4.1 Differential Diagnosis 5 Meningioma Grading 6 Meningioma Relapse Risk Stratification 7 Molecular PET Imaging 8 Selected Tracers for PET Imaging in Meningioma Patients 8.1 Glucose PET 9 PET Ligands for Somatostatin Receptors 10 Amino Acid PET Tracers 11 Clinical Applications for PET Imaging 11.1 Meningioma Detection and Delineation 12 Radiotherapy Planning 13 Diagnosis of Meningioma Relapse 14 PET-Based Theranostics in Patients with Meningioma 15 Conclusions References Histopathology of Meningiomas 1 Introduction 2 Gross Pathology 3 Intraoperative Cytology 4 Histological Variants and Grading 4.1 Meningothelial Meningioma 4.2 Fibrous/Fibroblastic Meningioma 4.3 Transitional Meningioma 4.4 Psammomatous Meningioma 4.5 Angiomatous/Vascular Meningioma 4.6 Microcystic Meningioma 4.7 Secretory Meningioma 4.8 Lymphoplasmacyte-Rich Meningioma 4.9 Metaplastic Meningiomas 4.10 WHO Grade 2 and Grade 3 Meningiomas 4.11 Atypical Meningioma 4.12 Clear Cell Meningiomas 4.13 Chordoid Meningioma 4.14 Anaplastic/Malignant Meningioma 4.15 Papillary Meningioma 4.16 Rhabdoid Meningioma 4.17 Rare Morphological Variants 5 Immunohistochemistry 6 Electron Microscopy 7 Differential Diagnosis References Skull Base Meningiomas 1 Introduction 2 Meningiomas of the Anterior Skull Base 2.1 Olfactory Grove Meningiomas 2.2 Meningiomas of the Planum Sphenoidale 2.3 Tuberculum Sellae Meningiomas 2.4 Orbital or Spheno-Orbital Meningiomas 3 Meningiomas of the Middle Skull Base 3.1 Clinoidal Meningiomas 3.2 Medial Sphenoid Wing Meningiomas 3.3 Cavernous Sinus Meningiomas 3.4 Middle Fossa/Temporobasal Meningiomas and Meningiomas of the Lateral and Middle Third of the Lesser Sphenoid Wing 4 Meningiomas of the Posterior Fossa Skull Base 4.1 Petrosal Retromeatal Meningiomas 4.2 Meatal or Cerebellopontine Angle Meningiomas 4.3 Petroclival Meningiomas 4.4 Meningiomas of the Jugular Tubercle and Jugular Foramen 4.5 Meningiomas of the Foramen Magnum 5 Final Conclusions References Spinal Meningiomas 1 Introduction 2 Epidemiology 3 Pathology 4 Genomic Landscape of Spinal Meningiomas 5 Clinical Presentation 6 Diagnosis 7 Treatment 7.1 Surgical Resection 7.2 Adjuvant Therapy 7.3 Emerging Therapies 8 Conclusion References Surgical Therapy of Non-Skull Base Meningiomas 1 Introduction 2 Preoperative Considerations 2.1 Indications for Treatment 2.2 Preoperative Assessment 3 Surgical Considerations Based on Location 3.1 Convexity Meningiomas 3.2 Parasagittal Meningiomas 3.3 Parafalcine Meningiomas 3.4 Tentorial Meningiomas 3.5 Intraventricular Meningiomas 4 Conclusion References Radiotherapy for Meningioma 1 Evolution of Radiotherapy for Meningioma 2 Radiotherapy Modalities and Techniques 2.1 Stereotactic Radiosurgery (SRS) 2.2 3D-Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) 2.3 Particle Therapy 2.4 Brachytherapy 3 Target Delineation and Dose Prescription 3.1 Stereotactic Radiosurgery 3.2 External Beam Radiotherapy (IMRT and 3D-CRT) 4 Radiotherapy Outcomes 4.1 Primary Fractionated Radiotherapy 4.2 Adjuvant External Beam Radiotherapy for Meningioma 4.3 Stereotactic Radiosurgery 4.4 Brachytherapy 5 Toxicity 6 Practical Considerations and Guidance References Stereotactic Therapies for Meningiomas 1 General Aspects of Meningiomas 2 Wait-and-Scan Strategy and Multimodal Management 3 Microsurgical Resection 4 Radiation Therapy 5 Stereotactic Radiosurgery 5.1 History of Stereotactic Radiosurgery 5.2 Indications for Stereotactic Radiosurgery 5.3 Therapeutical Dose and Dose Constraints 6 Stereotactic Radiosurgery for Benign Meningiomas (WHO 1) 6.1 Particular Anatomical Locations Petroclival Meningiomas Cavernous Sinus Meningiomas 7 Atypical and Anaplastic Meningioma WHO 2 and 3 7.1 Atypical Meningioma WHO 2 7.2 Anaplastic Meningiomas WHO 3 8 Brachytherapy for Meningiomas References Advances in Central Nervous System Tumor Classification 1 Importance of Molecular Classification of CNS Tumors 2 The WHO Meningioma Classification – Current State 3 Molecular Classification of Meningiomas 4 Molecular Signatures to Predict Meningioma Recurrence and Progression 5 Management Implications 6 The Future of CNS (or Meningioma) Tumor Classification 6.1 Liquid Biopsy 6.2 Radiogenomics 7 Final Remarks – Merging the Future with the Present Bibliography Genomic Landscape of Meningiomas 1 Introduction 2 Genomic Alterations in Meningiomas 2.1 Copy Number Alterations 3 Gene Mutations 3.1 Neurofibromin-2 (NF2) 4 TRAF7, AKT1, KLF4 5 Hedgehog Signaling Pathway 6 PIK3CA 7 POLR2A 8 SWI/SNF, SMARCB1, SMARCE1 9 BAP1 10 TERT 11 FOXM1 12 CDKN2A/B 13 Multiomic Classification of Meningiomas 14 Conclusion References Radiation-Induced Meningiomas 1 Introduction 2 Epidemiology 3 Pathology 4 Clinical Presentation 4.1 Signs and Symptoms 5 Location and Multiplicity 6 Genomics 7 Management 7.1 Surgery 8 Stereotactic Radiosurgery 9 Observation/Conservative Management 10 Recurrence and Progression 11 Conclusions References The Epigenetic Landscape of Meningiomas 1 Introduction 2 Epigenetic Changes 2.1 Altered DNA Methylation 3 MicroRNA Expression 4 Histone and Chromatin Modifications 5 The Meningioma Enhancer Landscape 6 Conclusion References Immune Profiling of Meningiomas 1 Introduction 2 Tumor Microenvironment of Meningiomas 3 PD-L1 in Meningiomas 4 Conclusions and Future Directions References Preclinical Models of Meningioma 1 Meningioma Cells Lines as Work Horse Models for Cancer Research 2 The Mutational Landscape of Meningioma Cell Lines 3 Xenograft Models for Preclinical Assessment of Anticancer Drugs 3.1 Heterotopic Xenograft Models 3.2 Orthotopic Xenograft Models and Imaging Methods 4 Genetically Engineered Mouse Models to Mimic Meningioma Progression 4.1 Ex Vivo Models for Precision Medicine References Novel Medical Therapies in Meningiomas 1 Introduction 2 Breakthroughs in Meningioma Biology 2.1 Meningioma Genetics 2.2 Meningioma Immunobiology 3 Prior Studies of Systemic Agents in Meningiomas 3.1 Chemotherapy 3.2 Growth Hormone 3.3 Somatostatin 3.4 Hormonal Therapy 3.5 Interferons 4 Novel Molecular Targets and Emerging Systemic Therapies in Meningiomas 4.1 Novel Small Molecule Inhibitors 4.2 Immunotherapy 4.3 Other Novel Approaches 5 Conclusion References Immunotherapy for Meningiomas 1 Introduction 1.1 Immune Checkpoint Inhibition 1.2 Vaccination 1.3 Cellular Therapies 1.4 T Cell Engaging Therapies and Immune Conjugates 1.5 Oncolytic Virotherapy 2 Conclusion References Health-Related Quality of Life in Intracranial Meningioma: Current Evidence and Future Directions 1 Introduction 2 Impact of the Tumor 2.1 Comparison with Healthy Controls and Normative Data 2.2 Comparison with Other Brain Tumor Patients 3 Impact of Treatment 3.1 Surgery 3.2 Radiotherapy 4 Determinants for HRQoL: Internal Factors 4.1 Association Between Symptoms, Global HRQoL, and Survival 4.2 Biological Variables: Tumor Characteristics and Comorbidities 4.3 Sociodemographic Characteristics 5 Interventions to Improve HRQoL: External Factors 5.1 Interventions for Patients to Improve Symptoms and Impairments 5.2 Interventions for Patients to Improve Activity Limitations and Participation Restrictions 6 Caregiver Burden 6.1 Intervention for Caregivers 7 Future Directions 7.1 Initiatives to Standardize the Design, Analysis, Reporting, and Interpretation of HRQoL Results in Meningioma 7.2 Survivorship Issues (Long-Term Follow-Up) 7.3 Improving Meningioma Care 8 Conclusions References Index