POSTGRADUATE
SCHOOL OF MEDICINE
BRAIN METASTASES
Dr Sarah Smith
MDSC156: Acute Clinical Oncology
A MEMBER OF THE RUSSELL GROUP
CONTINUING PROFESSIONAL DEVELOPMENT
Brain Metastases
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Brain Metastases
It is estimated that between 20 - 50% of cancer patients will develop brain
metastases at some point during their disease course
The incidence of brain metastases is rising, however this is thought to be due
to more sensitive diagnostic procedures
Brain metastases may be located in all sites of the brain
Multiple metastases are found in approximately 50% of cases
Brain Metastases
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Brain Metastases
•
Not all metastatic tumour cells can generate a brain tumour
•
Brain metastases present a
particular problem in that
the metastatic cell must
cross the blood brain barrier
Netter's Illustrated Neuroscience (2003) D.L. Felten, R.F. Józefowicz
Brain Metastases
Brain Metastases
Some types of cancer
are more likely to
spread to the brain
• Lung
• Breast
• Skin (malignant melanoma)
• Bowel
• Kidney (renal)
Among patients with
lung cancer, the
estimate is as high as
50% for brain
metastases
• Adenocarcinomas
metastasize to the brain
more frequently than
squamous cell carcinomas
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Brain Metastases
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Contrast-enhanced T1-weighted MRI of a 67-year-old man with multiple brain metastases
originating from lung adenocarcinoma. Unsteady gait was the only presenting sign.
Note the ring-like enhancement of the largest lesion with central necrosis.
(Reproduced courtesy of Prof. D. Bale´riaux in Perz-Larrya and Hildebrand 2014)
Brain Metastases
Symptoms
• Not all brain tumours are symptomatic
• Symptoms can include:
•
Vertigo
•
Paraesthesias
•
Headaches
•
Visual changes
•
Cognitive, personality and
behavioural changes
•
Bells palsy
•
Nausea and vomiting
•
Seizures
•
Memory loss
•
Confusion
•
Lethargy
•
Ataxia
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Brain Metastases
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Pathogenesis of Brain Metastases
•
Metastasis is a multistage process in which malignant cells spread from the
tumor of origin to colonize distant organs, following a sequence of steps
which includes: local invasion, intravasation, survival in circulation,
extravasation and tissue colonization)
• The mechanisms that allow tumour cells to colonize the brain are still not
fully understood
• Several molecular mechanisms contributing to brain metastasis have being
revealed including multiple genes
www.youtube.com/watch?v=bdWRZd19swg&title=Introduction%20to%20Cancer%20Biology%20(Part%203):%20Tissue%20Invasion%20and%20Metastasis
Brain Metastases
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A.F Eichler, et al (2011) The biology of brain metastases; translation to new therapies Nature Reviews Clinical Oncology, 8, 344-356
Brain Metastases
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Diagnosis
•
Diagnosis is made through imaging and can include:
•
CT with and without Iodine contrast
•
MRI
•
Standard MRI includes T1WI (T1-weighted imaging) with and without contrast agent, T2WI (T2weighted imaging), and FLAIR (fluid-attenuated inversion recovery) sequences.
•
•
Diffusion-weighted MRI (DW-MRI)
•
Perfusion MRI
Brain positron emission tomography (PET) using 18 F-fluorodeoxyglucose (18 F-FDG) or amino acid
tracers can be useful to differentiate hypometabolic postradiation focal necrosis from hypermetabolic
malignant lesion
•
Diagnostic biopsy can also be necessary dependent upon the location of the tumour
Brain Metastases
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Treatment
There are several therapeutic
options which guide treatment
these include:
The size, location and
type of tumour
The patient's general
health
The extent, control and
pathology of the
primary tumour
Prior anticancer
treatments
Brain Metastases
Treatment
Radiation
Radiation treatment to the whole brain is often used to treat
tumours that have spread to the brain, especially if there is more
than one tumour
Surgery
Can be used to remove the tumour or the tumour can be debulked
Chemotherapy
An option, but usually not as helpful as surgery or radiation as only
some tumours respond to chemotherapy.
Stereotactic radiosurgery
A form of radiation therapy which focuses high-power x-rays on a
small area of the brain.
Whole Brain Therapy
Radiation therapy to the whole brain, has approx 75 % success rate
(WBT)
Drugs
Can include corticosteroids, osmotic diruetics, anti-convulsants
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Brain Metastases
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Combined Therapies
• Combining therapies is possible to provide optimal outcome, however this is
determined by a number of factors;
Patient age
Functional status
Primary tumour type
Extent of extracranial disease
Prior therapies
Number of intracranial lesions
Brain Metastases
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Combined Therapies
• Combining therapies often includes chemotherapy with radiotherapy i.e.
•
Whole brain therapy + chemotherapy
•
Stereotactic radiosurgery + chemotherapy
• However it is not limited to this as other combinations can be equally effective i.e.
•
Whole brain therapy + stereotactic therapy
• The decision to combine therapies must be considered fully as there are numerous
disadvantages including increased cellular toxicity, which can have the adverse effect
on patient outcome and prognosis.
Brain Metastases
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Management
Anticancer treatments
Follow up imaging
Drugs that are not specifically anticancer provide supportive treatments and are
used in the management of patients with brain metastases include:
•Corticosteriods
•Antiepileptic drugs
•Anticoagulants
Brain Metastases
Prognosis
• Prognosis is often poor
• There are 4 defined prognostic factors for the survival of
patients with brain metastases:
1.
Age
2.
Extent of systemic disease
3.
Number of brain metastases
4.
Performance status
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Brain Metastases
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References
•
Dawe et al (2014) Brain Metastases in Non Small-Cell Lung Cancer, Clin. Lung Canc.,
15, 249-57
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Lombardi et al (2014) Systemic treatments for brain metastases from breast cancer,
non-small cell lung cancer, melanoma and renal cell carcinoma: An overview of the
literature, http://dx.doi.org/10.1016/j.ctrv.2014.05.007
•
Seoane and Mattos-Arruda (2014) Brain metastasis: New opportunities to tackle
therapeutic resistance, http://dx.doi.org/10.1016/j.molonc.2014.05.009
•
Perz-Larrya, Hildebrand (2014) Handbook of Clinical Neurology, Vol. 121 (3rd series)
Neurologic Aspects of Systemic Disease Part III, 1143-1157
•
Harouaka et al (2013) Circulating tumor cell enrichment based on physical
properties, J. Lab. Autom., 18 (6)
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A MEMBER OF THE RUSSELL GROUP