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An Overview of Glioblastoma (GBM). Marci Klaassen, MSN and Allen Waziri, MD Department of Neurosurgery University of Colorado School of Medicine. Background. Increased metabolic demand. Necrosis. Microvascular proliferation. Glioblastoma : the miserable truth.

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an overview of glioblastoma gbm

An Overview of Glioblastoma (GBM)

Marci Klaassen, MSN and Allen Waziri, MD

Department of Neurosurgery

University of Colorado School of Medicine

glioblastoma the miserable truth

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
basic pathology and physiology
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
rapidly progressive neurological symptoms depending on the location of the tumor
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
Brain Tumor Symptoms
  • Irritation
    • Seizures
  • Pressure
    • Edema
    • Direct mass effect
  • Destruction
slide9

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

recovery from surgery
Recovery from Surgery
  • Post-operative pain
  • Anti-epileptic medications
  • High potency steroids
  • Treatment planning
  • Wound healing
  • Ramifications of diagnosis:
    • Emotional
    • Social
    • Financial
side effects
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
disease progression
Disease Progression
  • Tumor recurrence
  • Additional treatment
  • Progression of neurological symptoms
  • Decreased ability to function independently
  • Death
experimental options for gbm
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
slide16

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

slide18

SUPPRESSION OF ENDOGENOUS CELLULAR IMMUNITY

GBM

Neutrophil activation

SUPPRESSION OF VACCINES/IMMUNOTHERAPY

slide19

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