Primary and secondary brain tumours Flashcards
Incidence of all brain tumours
~20:100,000
16th most common registered adult cancer
2nd most common paediatric cancer
Incidence of primary tumour
~8:100,000
Presentation of a brain tumour - 3 cardinal presenting symptoms
Symptoms of raised ICP (headache, reduced conscious level, nausea and vomiting)
Progressive neurological deficit
Epilepsy
Causes of raised ICP (intracranial pressure)
Headache
Drowsiness
Vomiting
Features of raised ICP headache
Worst on waking from sleep in morning
Increased by coughing, straining and bending forwards
Sometimes relieved by vomiting
Cardinal physical sign of raised ICP and its cause
Papilloedema Due to obstruction of venous return from the retina Loss of crisp optic nerve head margins Venous engorgement Retinal oedema Haemorrhages
What is papilloedema
optic disc swelling that is caused by increased intracranial pressure
Focal neurological deficits
Motor deficit (this includes ataxia) Sensory deficit Speech deficit Visual deficit Deafness Deteriorating memory Personality change
Features of epilepsy as a result of brain tumour
Sinister when of recent onset
Focal seizures more common with tumours:
Motor, Sensory, Temporal lobe pattern
(olfactory aura or ‘deja vue’)
Types of brain tumours
Primary
Secondary
Are primary or secondary tumours more common
Secondary
Aetiology of secondary tumours
Non small cell LUNG 24%
Small cell LUNG 15%
Breast 17% Melanoma 11% Renal cell 6% GI 6% Unknown primary 5%
Secondary brain tumour treatment options
Surgery
Radiotherapy
Chemotherapy
Best supportive care
When is surgery considered as an option for brain cancer patients
Absent or controlled 1st degree disease i.e. survival >1/4
Age <75
Good performance status
Median survival from surgery
13.4 months
(1 yr survival 56%)
(5yr survival 15%)
Surgical failure rate for brain tumour
52% of radiation group had brain recurrence
28% of surgery and radiation group had recurrence
What cell type are majority of primary brain tumours from
Glial cells
Types of primary brain tumours
Astrocytoma (85-90%)
Oligodendroglioma (~5%)
Others: medulloblastoma, central neurocytoma etc
WHO Grading of Gliomas
Grade I - Paediatric tumour/pilocytic astrocytoma
Grade II - Premalignant tumour (benign)
Grade III - Anaplastic astrocytoma (cancer)
Grade IV - Glioblastoma multiforme (GBM) - Most common phenotypes
True or False:
Given enough time all gliomas will progress inexorably to become GBM (glioblastoma multiforme)
True
Pathophysiology to malignant glioma
2 ways:
1. (More Common) Initial genetic error is of glucose glycolysis:
Mutation of isocitrate dehydrogenase 1 (IDH-1). Results in excessive build up of 2-Hydroxyglutarate. Which triggers genetic instability in glial cells and subsequent inappropriate mitosis.
2. No IDH mutation:
Catastrophic genetic mutation. Very poor prognosis even for ‘low grade’ tumours.
Survival of glioblastoma
At present under 20% survive of patients with GBM survive more than 18 months from diagnosis even with ‘aggressive therapy’
Good prognostic factors of glioblastoma patient
Age under 45-50 years
Aggressive surgical therapy
Good performance post surgery
Tumour that has transformed from a previous low grade tumour (secondary GBM)
MGMT mutant – which means they should respond chemoRx
Poor prognostic factors of glioblastoma patient
> 50 years
Post-surgery: Poor neurological function - drowsy, headache, focal neurology
Non radical surgical treatment
De novo disease: Primary GBM
MGMT ‘wild type’ - no predicted response chemoRx
Glioblastoma therapy
Resective surgery if possible
Adjuvant chemotherapy with TEMOZOLOMIDE at time of RT (60Gy)
Followed up by Temozolomide chemoRx
6 cycles (5/7 every 4/52 for 6/12 or to progression).
How does Temozolomide work?
Prodrug activated by HCl
Crosses BBB
Methylates guanine in DNA making replication impossible at this base site
How can you reverse Temozolomide
MGMT (Methyl-Guanine-Methyl-Transferase)
MGMT reverses guanine methylation by Temozolomide
Example of tumour resistance to Temozolomide (enzyme that can be made by cancerous cells)
Unproven treatment of glioblastoma
Anti angiogenic Rx (Bevazicumab ‘AVASTIN’) - tho doesnt benefit survival time
Anti angiogenic agent that shuts down tumour blood supply
When would you use ‘suicide gene therapy’ and how does it work
Involves inocculation of tumour with replication deficient HSV-1 retrovirus. Wild type HSV-1 replicates exponentially and causes encephalitis. Replication deficient (modified) HSV-1 fails to replicate in normal brain – i.e. non virulent. Modified HSV-1 replicates with the rapidly dividing cells (GBM) - subsequent oncolysis results in release of progeny virus – selective replication competence Tumour cells killed normal brain cells unaffected.
What is dexamethasone
Most powerful synthetic steroid
Rapidly improves brain performance in all brain tumours
Reduces tumour inflammation/oedema
Palliative care for glioblastoma
MacMillan nurses
Hospice
Complementary therapy
What grade is a benign glioma
Low grade glioma II
Epidemiology of benign glioma
Disease of young adults (rare >45 years old)
Commonly presents with seizures as first symptom
Median survival from diagnosis of benign glioma
5-7 years
Cause of deterioration from benign glioma
Tumour transformation to a malignant phenotype.
Progressive mass effect due to slow tumour growth.
Progressive neurological deficit from functional brain destruction by tumour.
Survival from oligodendroglioma
10-15 years survival
Features of oligodendroglioma
Will transform to anaplastic (WHO 3) variant eventually
Can transform to GBM
Genetic defect in chromosome 1 and 19
Treatment of oligodendroglioma
(triple agent) chemotherapy
WHO Grading of Gliomas
Grade I - Paediatric tumour/pilocytic astrocytoma
Grade II - Premalignant tumour (benign)
Grade III - Anaplastic astrocytoma (cancer)
Grade IV - Glioblastoma multiforme (GBM) - Most common phenotypes
Prognosis of each grade of glioma
I - good
II - >5 years
III - 2-5 years
IV - <1 year
Describe grade I glioma
Completely benign
Paediatric tumour - mainly see in children
Describe grade II glioma
Premalignant tumour
Describe grade III glioma
CANCER! - Malignant
See active growth & mitotic activity on microscope
Describe grade IV glioma
MOST COMMON PHENOTYPE
Active growth, mitotic activity, necrosis (since growing so fast, it falls apart) and vascular
proliferation
VERY MALIGNANT
Types of treatment of brain tumour
Surgical
Medical
Radiotherapy
Treatment of brain tumour (surgical, medical and when to use radiotherapy)
Surgery: Exploration, removal or biopsy (meningiomas can be fully removed without incident)
Radiotherapy: Gliomas and radiosensitive metastases
Medical: Cerebral oedema can be reduced with corticosteroids. Epilepsy treated with anticonvulsants.
Medical treatment of cerebral oedema
Corticosteroids
Medical treatment of epilepsy
Anticonvulsants
Diagnosis of brain tumour
CT and MRI
Positron Emission Tomography to find occult metastasis
