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Multiforme
DR.KATTA CHARU GOUTHAM REDDY
Glioblastom
a
Multiforme
Definition
Glioblastoma
multiforme (GBM),
also known as
glioblastoma and
grade IV astrocytoma,
is the most common
and most aggressive
cancer that begins
within the brain.
Objectives
1.Anatomy
2.Physiology
3.Natural History of Disease
4.Diagnostic Work Up
5.Classification
6.Disease Management by Stage
7.Radiation Treatment Techniques
8.Sequelae of Treatment
9.Follow Up
10.Recurrence Management
Anatomy-Cerebrum
The cerebrum is the largest part of the
brain.
The cerebrum is made up of the
1. Two cerebral hemispheres and
their cortices, (the outer layers of
grey matter)
2. Underlying regions of white matter
3. Subcortical structures
(hippocampus, basal ganglia and
olfactory bulb)
Cerebral Cortex
The cerebral cortex, the outer layer
of gray matter of the cerebrum
Surface of folds to create gyri
(ridges) and sulci (furrows) to
increase the surface area.
The cerebral cortex is classified into
four lobes:
Frontal,
Parietal,
Temporal,
Occipital Lobes(Calcirine Sulcus
Divides occipital and Parietal
Subcortical Structures-Basal
Ganglia
The basal ganglia (or basal nuclei)
comprise multiple subcortical nuclei
1. dorsal striatum (caudate ,putamen)
2. ventral striatum (nucleus
accumbens . olfactory tubercle),
3. globus pallidus,
4. ventral pallidum,
5. substantia nigra
6. subthalamic nucleus
Microscopic Anatomy
Cell Type
Function
Neuron
Oligodendroc
yte
Myelination of CNS
neuron
Astrocyte
Multiple functions
Microglia
Macrophages of Brain
Ependymal
Cells
movement of CSF,
separate ventricles and
the CSF from the
neuronal environment
Astrocytes
1. Structural Framework For Neuronal
Cells
2. Integrity Of The Bloodbrain Barrier
3. Taking Up, Storing And Releasing
Some Neurotransmitters
4. Neuronal Guidance During
Development
5. Adult Neurogenesis.
6. Presenting Antigen To The Immune
System
Functions
Frontal
1.
2.
3.
4.
Memory Formation
Emotion
Decision Making
Personality
processing, integration,
interpretation, etc. of Vision
and Vision Stimuli
Speech
Area
Function
Defect
Brocas Area
Left Frontal
Lobe
Controls facial
neurons,
speech, and
language
comprehension
ability to
comprehend
speech, but the
decreased r ability
to speak and form
words
Wernicke Area
Left Temporal
Lobe
Language
comprehension.
Words and
sentences are not
understood,
sentence formation
non-sensical
Arcuate
Fasuculus
A white matter
Brocas Area
and Wernickes
Area.
Allows for
coordinated,
comprehensible
speech
Conduction Aphasia
- auditory
comprehension and
speech articulation
are preserved,
difficult to repeat
heard speech
Motor Functions
Area
Functions
Premotor Cortex
(Precentral Gyrus)
Primary
Site involved with
Somatosensory Cortex processing of tactile and
Postcentral Gyrus)
proprioceptive
information.
Somatosensory
Association Cortex
Limbic System
1. Emotional brain :Emotional and
motivational aspects of behavior.
2. Provides emotional component to
learning process: Especially the
amygdala.
3. Associated with memory
Especially the hippocampus.
4. Associated with pain/pleasure,
rage
Molecular Pathogenesis of
Glioma
Oncogenes
EGFR
(Epidermal Derived
growth Factor
Receptor)
PGDFR
Platelet Derived
Growth Factor
Receptor
Molecular changes in
Glioblastoma
Gene
Function
LOH
Loss of heterozygosity on chromosome arm 10q is the most frequent gene alteration it occurs in
60-90% of cases. specific for glioblastoma multiforme associated with poor survival.
p53
The p53 gene appears to be deleted or altered in approximately 25-40% of all glioblastoma
multiform, more commonly in secondary glioblastoma multiformes.
EGFR
more common in primary glioblastoma, with mutations appearing in 40-50% of these tumours
MDM2
Amplification or overexpression of MDM2 constitutes an alternative mechanism to escape from p53regulated control
Overexpression of MDM2 is the second most common gene mutation in glioblastoma
multiformes and is observed in 10-15% of patients
PDGF
The PDGF gene acts as a major mitogen for glial cells by binding to the PDGF receptor (PDGFR).
Amplification or overexpression of PDGFR is typical (60%) in the pathway leading to secondary
glioblastomas.
PTEN
PTEN (also known as MMAC and TEP1) encodes a tyrosine phosphatase located at band 10q23.3.
cellular phosphatase, turning off signaling pathways, is consistent with possible tumor-suppression
action.
When phosphatase activity is lost because of genetic mutation, signaling pathways can become
activated constitutively, resulting in aberrant proliferation.
PTEN mutations have been found in as many as 20% of glioblastomas, more commonly in primary
glioblastoma multiformes
Primary
Secondary
Definition
De novo
From LGG
Age
Older
Younger
(<45)
Genetics
EGFR
P53 PGDF
overexpressi IDH1
on
mutation
Clinical
worse
Better
Corpus
Callosum
Other Pathways
of spread
Ependymal,
Subpial Spinal Cord Metastasis
Intramedullary
Meningeal Spread
Extra neural Metastases
Clinical Presentation
Generalized
Focal
1. Headache
1.
2.
3.
4.
4.Unilateral Weakness
5.Mental changes
because of
Weakness
Language dysfunction,
Sensory loss
Hemorrhage
Physical Examination
Aspect
Points to be noted
Consciousness
Digress of Alertness
Symptoms of raised of intracranial
pressure
Visual Symptoms
Field of Vision
Normal
Speech
Sensory Examination
Motor Examination
Imaging
Objectives
Initial diagnosis of neoplasia
Characterization of cell type
Anatomical localization
Staging tumor extent
Assistance in planning treatment
Biopsy guidance
Monitoring response to
treatment
CT Scan
1. Histological heterogeneity of these
lesions is reflected in the CT
appearances.
2. The typical finding is of a mass with a
thick ring of contrast enhancement
with surrounding low-density
edematous change.
3. Central low density indicates necrosis
and is seen in 95% of tumors.
4. Inhomogeneous patchy
enhancement throughout the mass
may be observed
Classification
Nonparametric recursive partitioning
analysis classified of patients into groups
with similar outcomes in malignant gliomas.
Age : Patients <50 years fare best
KPS 70
Normal Mental Status
Abnormal Mental Status
Molecular Classification of
Glioma
Treatment
Algorithm of
Glioblastoma
Multiforme
General Management-Cerebral
Edema
Glucocorticoids are used to control neurologic signs and symptoms caused by
cerebral edema.
Lower doses of steroids (e.g., 2 to 4 mg dexamethasone) twice daily have
been shown to be as effective as higher doses. Prolonged steroid use is
associated with multiple medical problems, and therefore steroids should be
discontinued or tapered to the lowest dose necessary, as soon as possible.
Dexamethasone is the most common corticosteroid used for historical
reasons and because of minimal mineral-corticoid effects.
As with all corticosteroids, a slow taper is necessary to prevent a rebound in
cerebral edema and also to allow the pituitaryadrenal axis to recover
General Management-Seizures
Patients with seizures require
anticonvulsants.
Prophylactic anticonvulsant use (in
patients who have never experienced a
seizure) remains controversial,
although practice guidelines from the
American Academy of Neurology
recommended against their use
because of lack of data.
Surgery
Goal is the safe removal of the largest possible
volume of tumor to establish a diagnosis and
relieve mass effect.
Frameless image-guided neuronavigation
systems are employed to localize subcortical
tumors along with intraoperative ultrasound
and MRI.
tumors may be removed en bloc via
circumferential dissection, but more frequently,
resection is effected in piecemeal fashion
Patients are routinely monitored in an intensive
care unit following a craniotomy. The first MRI is
obtained within 24 to 48 hours after surgery
before postoperative changes set in. The extent
of resection can be determined in this manner.