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

2. Background

3. Glioblastoma : the miserable truth
The most common primary brain tumor (~300 new cases in Colorado per year)
Incidence is highest in patients 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
Necrosis
Microvascular proliferation
Increased metabolic demand

4. 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

5. Clinical Presentation

6. 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:
Brainstem:
Double vision
Problems swallowing
Changes in speech

7. Brain Tumor Symptoms Irritation Pressure Destruction Seizures Edema
Direct mass effect
Destruction

8. Standard Treatment

9. 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

10. Clinical Course

11. Recovery from Surgery Post-operative pain Anti-epileptic medications
High potency steroids
Treatment planning
Wound healing
Ramifications of diagnosis:
Emotional
Social
Financial

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

13. Disease Progression Tumor recurrence Additional treatment
Progression of neurological symptoms
Decreased ability to function independently
Death

14. Experimental Therapy

15. 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

16. 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

17. Nov 2011

18. GBM SUPPRESSION OF ENDOGENOUS CELLULAR IMMUNITY Neutrophil activation
SUPPRESSION OF VACCINES/IMMUNOTHERAPY

19. A Randomized Placebo-Controlled Trial Exploring the Efficacy of Oral Arginine Supplementation to Improve Cellular Immune Function in Patients with Glioblastoma Multiforme

20. Thank you – questions?