An Overview of Glioblastoma (GBM)

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. Increased metabolic demand Necrosis Microvascular proliferation 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

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: • Visual impairment • Brainstem: • Double vision • Problems swallowing • Changes in speech

7. Brain Tumor Symptoms • Irritation • Seizures • Pressure • 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: 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

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. SUPPRESSION OF ENDOGENOUS CELLULAR IMMUNITY GBM 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?