Dr Kevin Patterson
TQEH
EPIDEMIOLOGY
SA CANCER REGISTRY 2003
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119 new cases “cancer of the
brain”(primary malignant tumours arising
in the brain)
67 male, 52 female
9 in the 15-19 age group
24 in 20-44 age group
Remainder (86) 45 + age group
CONT.
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50 (42%) in >65 yo age group
Incidence increases with age particularly
for high grade tumours
TYPES OF TUMOUR
RAH neurosurgical data 1977-98
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80 % Astrocytoma
20% variety of other tumours including
oligodendroglioma, ependymoma, medullo
blastoma, other glial tumours not
otherwise classified and primary CNS
lymphoma
CONT.
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Majority in RAH data (90%) were high
grade tumours (GLIOBLASTOMA)
In terms of burden of disease in adults
high grade gliomas represent the largest
single group
Treatment Options
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Surgery cornerstone of initial management
Purpose of surgery is diagnostic and
therapeutic
Increasing evidence that extent of
resection (biopsy vs sub-total resection vs
total resection) impacts on outcome
Whats’s New in Surgery?
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Functional MRI (fMRI): This newer
type of MRI looks for tiny blood flow
changes in an active part of the brain. It
can be used to determine what part of the
brain handles a function such as speech,
thought, sensation, or movement. Doctors
can use this to determine which parts of
the brain to avoid when planning surgery
or radiation therapy.
Awake Craniotomy
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In some cases, tumors infiltrate parts of the
brain involved in movement or language. In such
cases, functional intraoperative mapping can
help identify the exact location of these
functions in the brain, enabling the surgeon to
avoid these areas and thereby minimize the risk
of harm to the patient during surgery. This
mapping process often requires that patients
remain awake during surgery, especially in the
case of speech mapping.
FGS
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Fluorescence-guided surgery. For this
approach, the patient drinks a special
fluorescent dye a few hours before
surgery. The dye is taken up mainly by the
tumor, which then glows when the
surgeon looks at it under special lighting
from the operating microscope. This lets
the surgeon better separate tumor from
normal brain tissue.
Radiotherapy
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Well established treatment for high and
lower grade tumours post surgery
May be primary treatment modality if
surgery inappropriate
Important to avoid radiation exposure to
“normal” brain because of TOXICITY
Standard RT delivered to tumour plus a
margin
RT delivery methods
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Three-dimensional conformal
radiation therapy (3D-CRT)
Intensity modulated radiation
therapy (IMRT)
Conformal proton beam radiation
therapy
RT delivery methods
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Stereotactic
radiosurgery/stereotactic
radiotherapy: This type of treatment
delivers a large, precise radiation dose to
the tumor area in a single session
(radiosurgery) or in a few sessions
(radiotherapy)
RT delivery methods
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In one approach, radiation beams are
focused at the tumor from hundreds of
different angles for a short period of time.
Each beam alone is weak, but they all
converge at the tumor to give a higher
dose of radiation. An example of such a
machine is the Gamma Knife.
RT delivery methods
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Another approach uses a movable linear
accelerator (a machine that creates radiation)
that is controlled by a computer. Instead of
delivering many beams at once, this machine
moves around the head to deliver radiation to
the tumor from many different angles. Several
machines with names such as X-Knife,
CyberKnife, and Clinac are used in this way for
stereotactic radiosurgery
RT delivery methods
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Brachytherapy (internal radiotherapy):
Unlike the external radiation approaches above,
brachytherapy involves inserting radioactive
material directly into or near the tumor. The
radiation it gives off travels a very short
distance, so it affects only the tumor. This
technique is most often used along with external
radiation. It provides a high dose of radiation at
the tumor site, while the external radiation
treats nearby areas with a lower dose.
Chemotherapy
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Commonly used as an adjunct to
surgery/RT (concurrent Temozolomide/RT
in GBM) or salvage
Problem with drug delivery is the BBB
Progress has been slow with a number of
negative trials reported in recent years
Angiogenesis inhibitors
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Bevacizumab (Avastin) most well
established
Approved and funded in USA for treatment
of relapsed GBM (not funded in Australia)
First line trials in combination with
standard CT/RT have not demonstrated a
survival advantage
Local Delivery
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Gliadel (carmustine) wafers
Implanted at time of surgery and slowly
release chemotherapy locally
Randomised trial has demonstrated
benefit over surgery/RT alone in GBM
No data to compare with standard
RT/Temozolomide
Local delivery
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For a newer method called convection enhanced
delivery, small tubes are placed into the tumor
in the brain through a small hole in the skull
during surgery. The tubing extends through the
scalp and is connected to an infusion pump,
through which chemo drugs can be given. This
may be done for hours or days and may be
repeated more than once, depending on the
drug used. This is still an investigational method,
and studies are continuing.
New approaches
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“Targeted” therapies, recognise a unique
genetic defect in the tumour that drives
growth or prevents cell death eg activating
EGFR mutations
Currently small molecule TKI’s and
monoclonal AB’s most well developed
Immunotherapy
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Need to “persuade” the immune system to
recognise tumour as foreign and mount an
immune response against the tumour
Personalised vaccines use tumour from
individual patients to prime immune cells
which are re-injected (dendritic cells)
Immunotherapy
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Protein vaccines which provoke an
immune response against a particular
molecule on the tumour eg EGFR VIII
This is a mutation of the EGFR receptor
present on 1/3 of GBM
Phase 3 trial currently ongoing
Other approaches
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Hypoxic cell sensitisers
Therapeutic viruses
Trials in Australia
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http://www.cancertrialsaustralia.com/Clini
cal-Trials-Register.aspx
Calvary North Adelaide, relapsed GBM,
carboplatin or lomustine in combination
with Buparlisib (PI3K inhibitor)
Support and Community Services
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Adelaide Brain Cancer Support group
Cancer Council………….
Huge unmet need for brain cancer coordinator
THANKYOU