An Overview of Glioblastoma (GBM)
Marci Klaassen, MSN and Allen Waziri, MD
Department of Neurosurgery
University of Colorado School of Medicine

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

Rapidly progressive neurological symptoms depending on the location of the tumor:
• Seizure
• Headache
• Frontal lobe:
– Paralysis
– Language/writing disturbances
– Personality /cognitive changes
• Parietal lobe:
– Altered sensation
– Language/reading disturbances
– Problems with spatial orientation
– Difficulty with calculations
• Temporal lobe:
– Emotional lability
– Memory loss
– Visual impairment
• Occipital lobe:
– Visual impairment
• Brainstem:
– Double vision
– Problems swallowing
– Changes in speech

• Irritation
– Seizures
• Pressure
– Edema
– Direct mass effect
• Destruction

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

• Post-operative pain
• Anti-epileptic medications
• High potency steroids
• Treatment planning
• Wound healing
• Ramifications of diagnosis:
– Emotional
– Social
– Financial

Chemotherapy:
• Nausea/vomiting
• Constipation
• Headache
• Rash
• Fatigue
• Joint pain
• Myelosuppression
– Anemia
– Infection
– Bleeding
Radiation Therapy:
Short-term:
•Hair loss
•Skin irritation
•Nausea
•Fatigue
Long-term:
•Neurological compromise
•Radiation necrosis

• Tumor recurrence
• Additional treatment
• Progression of neurological symptoms
• Decreased ability to function independently
• Death

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
• Convection-enhanced delivery
• Virotherapy
• Nanoparticles
• Immunotherapy – tumor vaccines, immunomodulation

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

GBM
SUPPRESSION OF ENDOGENOUS
CELLULAR IMMUNITY
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