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 Necrosis Microvascular proliferation Increased metabolic demand

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: 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

Brain Tumor Symptoms Irritation Pressure Destruction Seizures 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 Post-operative pain Anti-epileptic medications High potency steroids Treatment planning Wound healing Ramifications of diagnosis: Emotional Social Financial

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

Disease Progression 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 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

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

Thank you – questions?