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An Overview of Glioblastoma (GBM)
Marci Klaassen, MSN and Allen Waziri, MDDepartment 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:– Visual impairment
• Brainstem:– 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
• Post-operative pain• Anti-epileptic medications• High potency steroids• Treatment planning• Wound healing• Ramifications of diagnosis:
– Emotional– Social– Financial
Side Effects
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
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 cancerRequirements for an effective immune
response (and therefore effective immunotherapy):
Source of antigenClearly present in GBM – EGFRvIII, etc.
Immuno-Accessible environmentIs the brain a site of immunoprivilege? Not
really.
Functional Immune System
Nov 2011
Neutrophil activation
SUPPRESSION OF ENDOGENOUS CELLULAR IMMUNITY
SUPPRESSION OF ENDOGENOUS CELLULAR IMMUNITY
SUPPRESSION OF VACCINES/IMMUNOTHERAPY
SUPPRESSION OF VACCINES/IMMUNOTHERAPY
GBMGBM
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?