an overview of glioblastoma (gbm) marci klaassen, msn and allen waziri, md department of...

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?