Oligodendroglioma: Clinical Presentation, Pathology, Molecular Biology, Imaging, and Treatment

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Oligodendroglioma:

Clinical Presentation, Pathology, Molecular
Biology, Imaging, and Treatment
Copyright
Dedication
Contributors
Foreword
Section A: Clinical presentation and quality of life
1
Clinical presentation in adults-Brain
	Epidemiology
	Tumor classification
	Clinical features
		Mutant IDH and seizure
	Prognosis and survival outcomes
		RTOG 9802
		EORTC 26951 and RTOG 9402
	References
2
Clinical presentation of spinal oligodendrogliomas
	Introduction
	Clinical presentation
	Imaging
	Other studies
		Pathology
		Lumbar puncture
		Molecular signatures
	Conclusion
	References
3
Oligodendrogliomas-Atypical clinical presentations
	Introduction
	Optic pathway
	Ciliary body/retina
	Pineal region
	Primary intraventricular (IV) ODG
	Cerebellum
	Brainstem
	Congenital presentation
	Leptomeningeal involvement
	Gliomatosis cerebri
	Spinal cord
	Metastatic ODG to extracranial/extraneural sites
	References
4
Clinical presentation of pediatric oligodendrogliomas
	Introduction
	References
5
Seizures, oligodendrogliomas, and brain-tumor-related epilepsy
	Introduction
	Definition of epilepsy
	Epilepsy in oligodendroglioma: Epidemiology and incidence
	Detection, classification and documentation of seizures
	Epileptogenesis, biomarkers and seizures
	Pharmacoresistance
	Impact of AEDs
	Pharmacological interaction
	Impact of antitumor therapy on seizure control
	Quality of life in BTRE patients
	Neurocognitive evaluation and possible rehabilitative programs
	Choice of AEDs
	Prophylaxis
	Health economics and BTRE
	Conclusions
	References
	Further Reading
6
Living with oligodendroglioma
	Physical factors in QoL
		Treatment-related symptoms
		Functional status
		Seizures
		Headaches
		Nausea
		Fatigue
		Sleep
		Nutrition
		Exercise
	Cognitive-behavioral factors in QoL
		Cognitive impairment
			Surgery
			Radiotherapy
			Chemotherapy
			Seizures
		Employment
		Driving
		Cognitive rehabilitation
	Psychosocial factors in QoL
		Emotional distress
		Stress and coping
		Social support and caregiver burden
	Interventions
	References
Section B: Pathology and molecular biology
7
Origin and development of oligodendroglioma
	Introduction
	Cell of origin
	Cell division and fate decision
	Mechanism of regulation: stem cell niches
	Preclinical models
	Conclusion
	References
8
Histopathology and molecular biology of oligodendrogliomas
	Introduction
	Gross appearance
	Histologic appearance
	Grading
	Clinically relevant molecular markers
	Differential diagnosis
		Diffuse astrocytoma
		Oligoastrocytoma/mixed glioma
		Pilocytic astrocytoma
		Papillary glioneuronal tumor
	Dysembryoplastic neuroepithelial tumor
	Ganglioglioma
	Central neurocytoma
	Clear cell ependymoma
		Rosette-forming glioneuronal tumor of the fourth ventricle
		Inflammatory related lesions
	References
9
The role of biomarkers in the diagnosis and treatment of oligodendrogliomas
	Introduction
	Biology
	Treatment
	Summary recommendations
	Ongoing challenges and future directions
	Conclusions
	References
10
Prospects of translational proteomics and protein microarrays in oligodendroglioma
	Introduction
	Source of biospecimen understates proteome discovery
	Proteomic technologies for data acquisition
		Gel-based proteomics
		Mass spectrometry
			Instrumentation
			Proteomic approaches
			Quantitation strategies in proteomics
		Protein microarrays
			Types of protein arrays
			Microarray analysis
	Proteomics in oligodendroglioma research
	Conclusions
	References
11
Pathology of pediatric oligodendroglioma
	Introduction
	Clinical signs and symptoms
	Neuroimaging
	Pathology (gross and microscopic)
	Molecular
	Differential diagnosis
	Prognosis and treatment
	References
Section C: Neuro-imaging
12
CT imaging of oligodendroglioma
	Introduction
	References
13
Routine and advanced magnetic resonance imaging of oligodendrogliomas
	Introduction
	Diagnostic imaging of diffuse gliomas
		Basic principles
		Technical considerations
	Unique imaging features of oligodendrogliomas
		Lobar distribution
		Cortical involvement
		Margin
		Enhancement
		Multifocality
		Calcification
		Heterogeneous appearance
		Growth rate
		Response to treatment
	Advanced imaging of diffuse gliomas
	Features of advanced imaging in oligodendrogliomas
	Imaging in clinical trials
	Conclusion
	References
14
Advanced [11C]methionine and [18F]FDG positron emission tomography for diagnosis, treatment, and follow-up of ...
	Updated diagnostic criteria for oligodendrogliomas
	Clinical management of oligodendrogliomas
	Limitations of anatomic imaging
	PET in neuro-oncology
	[18F]FDG PET in neuro-oncology
	Amino acid PET in neuro-oncology
	Distinguishing tumor from nonneoplastic etiologies
	Differentiating oligodendrogliomas from astrocytomas
	Differentiation of low grade from anaplastic oligodendrogliomas
	Prognostic value of [11C]methionine PET
	Guiding stereotactic biopsy
	Defining tumor margins and surgical planning
	Role of [11C]methionine in radiation therapy and chemotherapy
	Tumor surveillance
	Conclusion
	References
15
Neuroimaging of pediatric oligodendrogliomas
	Epidemiology
	Location
	Clinical presentation
	Prognostic indicators
	Molecular analysis
	Neuroimaging
	Advanced neuroimaging
	Role of positron emission tomography (PET)
	Differential diagnosis
		Ganglioglioma
		Dysembryoplastic neuroepithelial tumor (DNET)
		Pleomorphic xanthoastrocytoma (PXA)
		Pilocytic astrocytoma
		Desmoplastic infantile ganglioglioma
	Management
	Follow-up imaging
	References
Section D: Surgical therapy
16
Oligodendrogliomas: Basic techniques in surgery
	Introduction
	Preoperative work-up
		Preoperative clinical testing
		Diagnostic imaging
		Image-guided stereotactic craniotomy and neuronavigation
		Anesthesia and systemic considerations for brain surgery
	Surgical resection
	Summary
	References
17
Oligodendrogliomas: Advanced techniques in surgery
	Introduction
	Surgical management
	Biopsy
	Biopsy technique
	Open surgical resection
		Preoperative planning
			Imaging
			Magnetic resonance imaging
			Functional MRI
			Magnetoencephalogram
			High-definition Fiber tracking
		Additional testing
		Advanced operative techniques
			Asleep craniotomy
			Awake craniotomy
			Anesthesia considerations
			Local anesthesia/scalp blocks
			Initial surgical steps (incision, craniotomy, and Dural opening)
			Intraoperative mapping and stimulation/electrocorticography
			Positive and negative mapping
			Intraoperative adjuncts
			Neuronavigation
			Chemiluminescence for resection of low-grade gliomas
			Intraoperative imaging adjuncts
			Laser interstitial thermal therapy
			Postoperative management
			Follow-up
	Summary
	References
18
Surgical management of 1p/19q co-deleted oligodendrogliomas WHO grade II and III
	Introduction
		Isocitrate dehydrogenase mutated, 1p/19q co-deleted oligodendrogliomas WHO grade II and III
		Tumor characteristics
	Preoperative diagnostic workup
		Magnetic resonance imaging
		Advanced imaging techniques
	The surgical perspective
	Microsurgical tumor resection
		Prognostic impact of surgery
		The risk of surgery
		Stereotactic biopsy
	Interstitial iodine-125 brachytherapy
	Future perspectives
	Conclusion
	Disclaimers
	Competing interests/disclosure
	References
19
Surgical results in anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA)
	Introduction
	Imaging
	Role of surgery
	Surgical outcomes
	Surgical adjuncts
	Conclusions
	References
20
Surgical management of pediatric oligodendroglioma
	Introduction
	Epidemiology and presentation
	Molecular and histologic classification and relevance to surgery
	Radiographic features
	Preoperative care and preparation
	Goals of surgery
	Surgical approaches and techniques
	Postoperative care
	Adjuvant therapy
	Outcomes
	Surveillance and recurrence
	Surgical clinical trials and research frontiers
	Conclusion
	References
Section E: Radiation therapy
21
Basic principles of brain tumor radiotherapy
	Introduction
		Primary CNS neoplasms
		Radiation therapy
		Foundations of radiotherapy: The 5 ``Rs´´
	Initial diagnosis and surgical management of brain tumors
	Steps in modern radiotherapy (Table 1)
		Patient simulation
		Treatment planning
		Dose reporting
		Quality assurance
		Initiation of treatment
		On-treatment visits and follow-up
		Specific treatment techniques
			Low-grade infiltrative astrocytomas and oligodendrogliomas
			High-grade gliomas
				Glioblastoma
				Anaplastic astrocytoma
			Radiation side effects
			Surveillance imaging
				Pseudo-progression
				Radionecrosis
			Recurrent glioma
	Future directions and conclusion
	References
22
Standard external beam radiation therapy for oligodendroglioma
	Introduction
	Practice of RT
		Low-grade gliomas: observation versus RT
		Low-grade gliomas: temozolomide alone
		Low-grade gliomas: RT versus chemotherapy
		Low- and high-grade gliomas: RT and chemotherapy
			Grade 2 gliomas and PCV chemotherapy
			Grade 3 gliomas and PCV chemotherapy
			Temozolomide with RT
		RT fractionation and dose
		RT: simulation, target volume, dose, treatment planning, and techniques
		Toxicities of RT
	References
23
Stereotactic radiosurgery in the management of oligodendroglioma
	Introduction
	Basics of radiosurgery
	Clinical use of radiosurgery for LGG
		SRS: upfront approach
		SRS for recurrent LGG (reirradiation)
		Radiosurgery treatment planning, delivery, and techniques
	References
24
Proton beam therapy for oligodendroglioma
	Introduction
	Background on protons
	The Role of Radiation Therapy for Oligodendroglioma
	Initial experience with proton therapy
	Neurocognitive outcomes
	Neuroendocrine outcomes
	Secondary malignancy
	Pseudo-progression and radiation treatment effect
	Technological improvements
	Cost
	Conclusions
	References
25
Interstitial brachytherapy treatment for oligodendrogliomas
	Introduction
	History of brain brachytherapy
		Procedure
		Isotopes
		Imaging advancement
	Rationale of brachytherapy
	Brachytherapy procedure
	Brachytherapy in gliomas
	Brachytherapy in oligodendrogliomas
	Brachytherapy for pediatric patients
	GliaSite brachytherapy
	Gliasite efficacy and safety (recurrent setting)
	Gliasite in the upfront setting
	Gliasite conclusion
	Brain brachytherapy toxicity and limitations
	Conclusion
	References
26
The role of radiation in pediatric oligodendrogliomas
	Introduction
	Treatment of pediatric oligodendrogliomas
	Clinical trial data-Grade II oligodendrogliomas
	Clinical trial data-Grade III anaplastic oligodendrogliomas
	Radiotherapy considerations
	Radiation therapy techniques
	Late effects of radiation
	Current best practices for radiotherapy in pediatric oligodendrogliomas
	References
Section F: Chemotherapy and immunotherapy
27
Basic principles of brain tumor chemotherapy
	Introduction
	Tumor burden and cell kill
	Gompertzian growth
	Drug resistance
	Cell-cycle specificity of chemotherapy agents
	Dose intensity
	Adjuvant and neoadjuvant chemotherapy
	Combination therapy
	Clinical trials
		Phase I trials
		Phase II trials
		Phase III trials
		Phase IV trials
	Assessment of response to chemotherapy
	Challenges of drug delivery
		Blood-brain barrier
		Efflux pumps
		DNA repair enzymes
	Strategies for improved CNS drug delivery
		Osmotic and chemical disrupt of the BBB
		MRI-guided focused ultrasound
		Radiation-induced BBB disruption
		Laser interstitial thermotherapy-induced BBB disruption
	BBB circumvention
		Drug modification
		Targeting receptor-mediated transporters
		Cancer-directed gene therapy
		Convection-enhanced delivery
		Implantable devices
		Intracerebrospinal fluid chemotherapy
	References
28
The use of PCV chemotherapy in oligodendrogliomas
	Background
	Evidence that led to definitive trials
	Retrospective insights
	Definitive trials
	Further discussion: Treatment of recurrent oligodendroglioma: Temozolomide or PCV? Either?
	Ongoing studies
	Deferred treatment
	Future directions
	Conclusion
	References
29
Temozolomide chemotherapy for oligodendroglial tumors
	Introduction
	TMZ for low-grade oligodendroglial tumors
	TMZ for anaplastic oligodendroglial tumors
	TMZ vs PCV for oligodendrogliomas
	References
30
Miscellaneous chemotherapy approaches to oligodendroglial tumors
	References
31
Molecular Therapy for Oligodendrogliomas
	Introduction
	The current status of systemic therapy for treatment of oligodendroglial tumors
	IDH inhibitors
	Everolimus
	PARP inhibitors
	Glutaminase inhibition
	Immunotherapy approaches
	Other promising targets
		DNA hypermethylation
		TERT activation
		Nicotinamide phosphoribosyltransferase inhibition
	Conclusions
	References
32
Bevacizumab for recurrent anaplastic oligodendroglial tumors
	Introduction
	Overview of oligodendroglial tumor classification integrating molecular characteristics
	Overview of oligodendroglial tumor treatment in the adjuvant and recurrent settings
	Bevacizumab use in glioblastoma
		Mechanism of action
		Dosing schedule in glioblastoma
		Toxicities
		Bevacizumab-related toxicities in glioblastoma
	Bevacizumab use in oligodendroglial tumors
	Practical issues regarding bevacizumab administration
		Which patients?
		Timing of bevacizumab administration and discontinuation
		Response assessment
	Conclusion
	References
33
Pediatric oligodendroglioma
	Introduction
	Epidemiology
	Clinical presentation
	Anatomy
	Histology
	Molecular drivers
	Therapy
		Surgery
		Chemotherapy
	Prognosis and outcome
	Conclusion
	References
34
Immune checkpoint blockade in glioma
	Introduction
	What are immune checkpoints?
	Predictors of checkpoint modulation efficacy
		Tumor mutational burden
		PD-1/PDL-1 expression
		T-cell infiltration
	Checkpoint combination strategies
		Dual-checkpoint blockade
		Radiation therapy
		Tumor vaccines
		Oncolytic virotherapy
	Challenges to checkpoint modulation in Glioma
		Toxicity
		Accurate evaluation of treatment response
		Preclinical models
	Oligodendrogliomas and immunotherapy: Future directions
	References
Index
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