Download GBM

An Overview of Glioblastoma (GBM)
Marci Klaassen, MSN and Allen Waziri, MD
Department of Neurosurgery
University of Colorado School of Medicine
Background
Glioblastoma : the miserable truth
• The most common primary brain tumor (~300 new cases in Colorado per
year)
• Incidence is highest in patients 45-55 years old – “prime of life”
• Median survival 15 months with best current therapy
• Hallmarks of tumor:
– Aggressive, infiltrative growth with necrosis of tumor (hypoxia)
– Significant vasogenic edema
– Copious microvascular proliferation
Increased metabolic demand
Necrosis
Microvascular proliferation
Basic pathology and physiology
• GBM starts from cells of the brain (stem cells?)
• Demonstrates infiltrative growth – “like mixing black and white sand
together” – makes differentiation from normal brain extremely difficult
• Most of the time occurs spontaneously (“primary”), but can also arise
from more low grade gliomas (“secondary)
• Virtually ALL low-grade tumors will progress to GBM, and clinical course
at that point is identical
• Few known risk factors
– Rare genetic traits (Li-Fraumini syndrome, etc.)
– Exposure to ionizing radiation (i.e. childhood treatment, etc.)
– No good data for association with cell phone use
Clinical Presentation
Rapidly progressive neurological symptoms depending
on the location of the tumor:
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Seizure
Headache
Frontal lobe:
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Parietal lobe:
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Emotional lability
Memory loss
Visual impairment
Occipital lobe:
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Altered sensation
Language/reading disturbances
Problems with spatial orientation
Difficulty with calculations
Temporal lobe:
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Paralysis
Language/writing disturbances
Personality /cognitive changes
Visual impairment
Brainstem:
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Double vision
Problems swallowing
Changes in speech
Brain Tumor Symptoms
• Irritation
– Seizures
• Pressure
– Edema
– Direct mass effect
• Destruction
Standard Treatment
Treatment of glioblastoma
Prognosis -> poor.
Treatment:
Surgery (debulking/cytoreductive)
Radiation (fractionated/IMRT)
Chemotherapy (Temodar, Avastin)
Tumor recurrence
Experimental therapy
DEATH (mean 15.4 months)
New treatment options are desperately needed
Clinical Course
Recovery from Surgery
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Post-operative pain
Anti-epileptic medications
High potency steroids
Treatment planning
Wound healing
Ramifications of diagnosis:
– Emotional
– Social
– Financial
Side Effects
Chemotherapy:
Radiation Therapy:
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Short-term:
•Hair loss
•Skin irritation
•Nausea
•Fatigue
Long-term:
•Neurological compromise
•Radiation necrosis
Nausea/vomiting
Constipation
Headache
Rash
Fatigue
Joint pain
Myelosuppression
– Anemia
– Infection
– Bleeding
Disease Progression
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Tumor recurrence
Additional treatment
Progression of neurological symptoms
Decreased ability to function independently
Death
Experimental Therapy
Experimental options for GBM
• “Biological” agents
– Designed to target specific receptors/growth
factors/pathways
– May be antibody, small molecule, etc. mediated
• Loco-regional therapy
– Gliadel wafers, brachytherapy
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Convection-enhanced delivery
Virotherapy
Nanoparticles
Immunotherapy – tumor vaccines, immunomodulation
Advantages of immunotherapy
Sensitivity, specificity and “memory”
“Natural” – the response of evolution to cancer
Requirements for an effective immune response
(and therefore effective immunotherapy):
Source of antigen
Clearly present in GBM – EGFRvIII, etc.
Immuno-Accessible environment
Is the brain a site of immunoprivilege? Not really.
Functional Immune System
Nov 2011
SUPPRESSION OF ENDOGENOUS
CELLULAR IMMUNITY
GBM
Neutrophil
activation
SUPPRESSION OF
VACCINES/IMMUNOTHERAPY
A Randomized Placebo-Controlled Trial Exploring the Efficacy of
Oral Arginine Supplementation to Improve Cellular Immune
Function in Patients with Glioblastoma Multiforme
Thank you – questions?