CNS Flashcards
When is surgery considered as treatment for intracranial mets
Solitary or large met (>3cm)
Mets causing obstruction - hydrocephalus or raised ICP
Cystic or necrotic mets where SRS is less likely to be effective
Where histology / diagnosis will be helpful
What are the criteria for SRS
An established diagnosis of cancer
Karnofsky performance status (KPS) >70
Absent or controllable primary disease (staging scans within last 3 months)
No previous SRS/SRT in the last 3 months
Life expectancy from extracranial disease >6 months
No pressure symptoms best relieved by surgery
Contrast enhanced MRI to evaluate cerebral metastases
Maximum combined treatment volume <20cc
Discussion at an MDT meeting
What are the histological signs of a GBM
Epithelial / vascular proliferation
Necrosis
What is the pathognomic mutation of an oligodendroglioma
1p19q co-deletion
What is the pathognomic mutation of an astrocytoma (presuming high grade ancestry)
ATRX loss
(ATRX retained = GBM)
What is bright on a T1 MRI
T1 -> CSF dark & Tumour dark
What is bright on T2 MRI & FLAIR
T2 -> CSF white & Tumour bright
T2 FLAIR -> CSF dark & Tumour bright with Oedema
How do low & high grade tumours enhance with contrast
Low grade tumours tend not to enhance. High grade tumours enhance (due to endothelial / vascular proliferation)
Where and for whom do pilocytic astrocytomas occur, and how do they present
Typically in children, low grade tumour
Tend to occur in cerebellum, causing obstruction and obstructive symptoms (pressure sx and headache)
What is the dose fractionation for craniospinal irradiation for a non-germinoma
overall 54Gy/30#
36Gy/20# to whole CSA and 18Gy/10# boost to tumour bed
What are the most common mutations seen in a pleomorphic xanthoastrocytoma
CDKN2A/B deletions (>90 percent)
BRAF V600E mutations (60-80 percent)
What is the benefit of adjuvant PCV in grade 2 gliomas
Buckner - 2016 NEJM
high risk Gr2 gliomas (<40yrs and subtotal resection or >40yrs) randomised to 6x adj PCV or not
PCV increased mOS to 13.3yrs from 7.8, and 10yr OS from 40% to 60%
When is immediate post-op RT indicated for a grade 2 glioma, vs at progression?
2 of:
Age >40
>6cm
Enhancement
Astrocytic
Crossing midline
Symptomatic
What is the adjuvant RT dose for a low grade glioma
54Gy/30#
What is the adjuvant dose for a grade 3 anaplastic oligodendroglioma
What adjuvant chemotherapy regime would typically follow
59.4/33#
Followed by 6x PCV adjuvant chemotherapy
12mth OS benefit to PCV adjuvantly
What is the adjuvant dose for a grade 3 anaplastic astrocytoma
What adjuvant chemotherapy regime would typically follow
59.4Gy/33#
Temozolamide x12 cycles adjuvantly
Based on the catnon trial
What is the post-operative RT regimen for a Gr4 GBM if <70 and PS0-1
And if <70 & PS2
And if >70
Concomitant CRT
60Gy/30# + concurrent TMZ (75mg/m2) & Co-trimoxazole prophylaxis 480mg M/W/F
Adjuvant chemotherapy
Adjuvant TMZ 150 - 200mg/m2 - D1-5 Q28 for 6 cycles
If <70 but PS2 - give RT only, without temozolamide
> 70: 40Gy/15# +/- concomitant tmz, and based on methylation status (based on Perry trial)
What RT dose is given to a butterfly glioma
30Gy/6# over 2wks, treating M/W/F
What is the mOS for a GBM? and based on what trial
Stupp trial
CRT & adj tmz vs RT alone
Median OS: 14.6m vs 12m and PFS 6.9m vs 5m
2yr OS: 26.5% vs 10.4%
Diffuse midline H3 K27-altered midline gliomas area considered what grade
Where are they typically located
How do they typically present
Always grade 4
most commonly in the pons, or other midline structures
(thalamus, brainstem - mesencephalon, pons, medulla, spinal cord)
Present with CN palsies, raised ICP and cerebellar sx.
What is the dose objective & constraint to brainstem
54Gy (objective)
59Gy (constraint)
What is the dose constraint to spinal cord
48Gy (objective)
50Gy (constraint)
What is the dose objective & constraint to optic nerves
50Gy (objective)
54Gy (constraint)
What is the dose objective & constraint to optic chiasm
50Gy - objective
54Gy - constraint
What is the dose objective & constraint to lens
6Gy objective
10Gy constraint
What is the dose objective & constraint to globes
O - 40Gy
C - 45Gy
What is the dose constraint to cornea
30Gy
What is the dose objective & constraint to retina
O - 45Gy
C - 50Gy
What is the dose constraint to lacrimal gland
Mean <26Gy
What is the dose constraint to cochlea
Mean <45Gy
What are the acute side effects of brain RT
Alopecia
Headache
Nausea/vomiting
What are the late side effects of brain RT
Neurocognitive effect – memory loss
Pituitary hypofunction
Optic chiasm damage – may cause blindness
Cataracts
2nd malignancies = 1%
What is the most common malignant tumour of the eye and ocular adenexa.
Non-hodgkin lymphoma - treat as primary CNS lymphoma
Where do ependymomas originate from
Where is the commonest site
How do they present
Ventricles - can occur anywhere within the neuraxis, and most commonly in the spine.
Most common intracranial site is the posterior fossa
Commonly cause obstruction, so tend to present with hydrocephalus
How are ependymomas graded
G1 - subependymomas or myxopapillary ependymomas
G2 - cellular, papillary, clear cell and tanycytic
G3 - anaplastic
What are the investigations for an ependymoma
MRI brain and whole spine
MRI post op for extent of resection
CSF 14 days post op to exclude circulating tumour cells
How is an ependymoma treated, and what determines adjuvant tx
surgery - resection of primary and mets
adjuvant tx if incompletely resected
if completely resected:
G1 - surveillance only
Gr2 - consider adjuvant tx
Gr3 - RT (adults = involved field only, children = whole CSA)
disseminated - CSRT with boost to all disease sites
How is the radio sensitivity of germinomas
Where in the CNS do they tend to occur
very radiosensitive
midline - pineal gland, suprasellar
What ix are required prior to starting treatment for a germ cell tumour
Ophthalmological assessment
Audiogram
GFR for patients due chemotherapy
Endocrine assessment as indicated
Fertility preservation
How is the management of germ cell tumour categorised?
Non-secreting germ cell tumour
NS-GCT - 80% secreting
For a non-secreting germ cell tumour, how is treatment divided
Localised
Metastatic
What is the treatment for a non-secreting localised germ cell tumour
Localised - 4x PIE chemotherapy (cisplatin, ifosfamide, etoposide), followed by CSRT
40Gy/25#overall, 24Gy/15# to CSA with 16Gy/10# boost to primary site
What is the treatment for a non-secreting metastatic germ cell tumour
No chemo
24Gy/15# CSA + tumour site boosts
For a secreting germ cell tumour, how is treatment divided
Localised
Metastatic
What is the treatment for a secreting localised germ cell tumour
4 x PIE (neo-adjuvant)
RT - 54Gy in 30# to primary (consider surgery for residual disease)
What is the treatment for a secreting metastatic germ cell tumour
Phase 1 CSA - 30Gy in 20#
Phase 2 boost - brain sites - 24Gy in 15#; spinal sites - 16Gy in 10#
Where do medulloblastomas tend to occur
How do they tend to present
Posterior fossa - midline for children, more likely lateralised for adults
Tend to present with symptoms of obstruction / raised ICP, or cerebellar symptoms
What are the four subtypes of medulloblastoma
WNT, SHH, Group 3, Group 4
How are medulloblastomas investigated / worked up
1/3 metastasise through the CNS, so pts need a spinal MRI and LP pre-operatively, or 14 days post op, to exclude circulating tumour cells
What investigations are done post-op
MRI for possible residual disease
If resectable, further surgeries are done for the most complete resection possible
How are medulloblastomas pts categorised post operatively
Standard or high risk
Standard risk
>3yrs age
<1.5 cm residual disease
CSF cytology negative
M0 (no metastases) on spinal staging
WNT and SHH groups
High risk
>1.5cm residual disease
CSF cytology positive (LP)
Metastases on staging imaging
Group 3 or 4 histology
What adjuvant treatment is given for medulloblastoma
CSA RT followed by chemotherapy
How is the CSA dose for medulloblastoma split
What adjuvant treatment is given following RT
High risk: 36Gy/20# to whole CSA followed by 18Gy/10# boost to primary site, with vincristine
Standard risk: 23.4Gy/13#, followed by primary site boost of 30.6Gy/17#, with vincristine
Overall primary tumour receives 54Gy/30#, with standard risk receiving less to the CSA
Following RT, adjuvant chemo is given
High risk - 8x PACKER chemotherapy
Lomustine, cisplatin, vincristine
Standard risk - modified PNET5 regime
Alternating cycles x8 of platinum/vincristine/lomustine, and cyclophosphamide
What is the prognosis of treated medulloblastoma
5YS approx 80%
10YS 60%
When is CSA RT indicated, and to what dose
All primitive neuroectodermal tumours (PNET):
Medulloblastoma - 54Gy/30# overall, according to risk
Supratentorial PNET
Pineoblastoma
Germ cell tumours:
Germinoma
Disseminated pilocytic astrocytoma
Ependymoma:
Gr3 adjuvantly for limited disease, or disseminated
What is the RT dose to the pituitary
What is the CTV, and margins
Primary RT: 45Gy/25# or 54Gy/30# if functioning
Adjuvant RT for macroscopic residual disease: 50.4Gy/28#
GTV = residual disease, and reconstructed pre-op disease
CTV = GTV +5mm, and whole pituitary fossa
PTV = CTV +3mm
How do low grade gliomas appear on MRI
T1 - typically hypo intense and do not take up contrast
T2 - Tumour is hyperintense, but no oedema
Hyperintense on FLAIR
How do high grade gliomas appear on MRI
Hyper-intense on T1, take up contrast
How does a pilocytic astrocytoma typically present
Most commonly occurs in children/TYA, and cerebellum, presenting with obstructive sx
How is a pilocytic astrocytoma treated
Localised
Tx: Surgery
Disseminated
Rare, usually arise in cerebellum, hypothalamic region, optic chiasm, near brainstem
Tx: Craniospinal RT
To start within 4 weeks of diagnosis
Ph1 - CSRT - 24Gy/12# over 4 weeks (1.8Gy/#)
Brain boost to tumour bed - 18Gy in 10# over 2 weeks
+/- SC boost to disease sites - 14.4Gy in 10# over 2 weeks
GTV - All visible enhancing tumour on T1W + gad
CTV - GTV + 5mm, and include all meningeal reflections throughout CSA
PTV - CTV + 5mm (but CTV-PTV margin depends on site within CSA - larger margins lower down the spine)
When should temozolamide and co-trimoxazole be held for deranged LFTs
ALT >148, ALP >325, bili >32 - hold co-trimox and tmp, until LFTs improved
ALT >245 / ALP >650 / Bilirubin >63 - discontinue both and continue RT alone
How does a craniopharyngioma typically present
Visual defect: lower quadrantanopia (tumour pushes down from above)
Hormone deficiency & Raised prolactin due to compression of pituitary stalk
Headaches
Obstructive hydrocephalus
Diabetes insipidus - loss of ADH
How is a craniopharyngioma treated
Surgery if possible
Primary RT if inoperable , or incomplete resection / recurrence.
RT 75-90% effective for local control
Dose:
Adjuvant - 50Gy/30#
Primary dose - 54Gy/30#
GTV-CTV: 5mm
Need to include all areas contacted by the tumour in the CTV
CTV-PTV: 3mm”
When is RT indicated for an ependymoma
And at what dose
How is metastatic ependymoma treated
Indications:
Incomplete resection if pt >3 yrs old.
G3 tumours or high risk grade 2
Relapsed disease if no previous RT
Adjuvant:
Intracranial - 54Gy in 30# (protons for children)
Spinal cord - 50-55Gy in 30-33#
Cauda equina - 54Gy in 30# - 59.4Gy in 33#
Metastatic:
CSRT -> 36Gy in 20# to CSA & Boost to individual sites of spinal disease up to 50.4Gy
If there is positive cytology and no gross visible disease outside the primary location, give craniospinal fields 45Gy/25# over 5 weeks followed by boost of 14.4Gy/8#”
What is the grading of ependymoma
G1-3
What proportion of pituitary macro adenomas are non-secreting
25%
What CNs are affected for a cavernous sinus tumour
III, IV, Va, Vb, VI
What are the treatment options for a pituitary tumour
If non-secreting and no threat to vision - observation
If secretary and threat to vision:
Medical - cabergoline/bromocriptin/lanreotide
Surgical - indicated if threat to vision or failure of medical mx
Surgical approach is typically trans-sphenoidal, but can be transcranial if there is superior extension
RT: failure of medical mx but not fit for surgery, recurrence or residual disease, or persistent hormone secretion
What is the outcome of surgery + RT to a pituitary tumour
80% relapse free survival at 20 years
What is the rate of optic neuropathy for pituitary RT
1%
How would a VS typically present
Unilateral sensorineural hearing loss
Balance problems
Involvement of the trigeminal nerve - facial pain or altered sensation
May expand into posterior fossa to occupy cerebellopontine angle -> compression of CN V, VII, VIII
What is the treatment for a VS
Only 50% grow - monitor for serial growth
Surgery for young pts and large / cystic tumours
RT - SRS 12Gy/1# or 50Gy/30# fractionated
What margin is used for VS SRS & fractionated
SRS:
GTV-CTV = 0mm
CTV - PTV=1mm
Fractionated:
GTV = CTV = visible tumour
CTV-PTV = 3mm
where are the typical sites of chordoma
What marker is sent
What is the complication
Spheno-occipital
Sacral spine
Brachyury
Chordomas tend not to metastasise but can be locally invasive and have a high rate of recurrence
What is the management of a skull base chordoma
Surgery and adjuvant RT, typically protons given location at the skull base
Chordomas receive 70Gy, chondrosarcomas 72Gy
CTV:
Clival lesion - GTV + entire clivus / sphenoid bone
Vertebral lesion - GTV + entire vertebral body
PTV:
CTV +3mm for skull base, 7mm elsewhere
Where do paragangliomas tend to occur
What investigation is needed before treatment
What mutation is associated
Paravertebral - tend to be chromatin positive and release catecholamines
In relation to the great vessels of the head and neck eg carotid bodies - tend to be chromatin negative and don’t release catecholamines
Need MRI brain and whole spine to exclude phaeochromocytoma
10% are associated with SDH-mutation
What is a glomus jugulare tumour
Paraganglioma arising from jugular foramen
Affect CN IX, X and XI
How are meningiomas classified
Gr1-3
How is a meningioma resection classified
Simpson classification
Stage 1 - Complete excision including dura and bone (tumour + dura + bone)
Stage 2 - Complete excision with co-angulation of dural attachment (tumour + dura)
Stage 3 - Excision of intradural tumour, without resection of it’s dural attachment (tumour alone)
Stage 4 - Partial removal, leaving intradural tumour in-situ
Stage 5 - Decompression only +/- biopsy
What are the indications for RT for a meningioma
Primary RT:
Option for Grade 1
Inoperable
Recurrence
Adjuvant RT:
Incomplete resection
Grade 3
Atypical histology
What RT dose is given to meningioma
SRS - 12-15Gy/1#
Fractionated:
G1 - 50Gy/30#
G2 - 55Gy/33# if Grade 2
G3 or sarcomatoid - 60Gy in 30#
What dose is given to an optic nerve sheath meningioma
54Gy in 30#
What are the RT volumes for a meningioma
Residual disease
GTV - Residual meningioma, hyperostotic bone and dural extension
CTV - GTV +1cm in plane of dura
If brain invasion present -> add 1cm into brain from brain/meningioma margin
Include all abnormal, hyperostotic bone not in GTV
PTV - CTV + 3mm
No residual disease
GTV - Pre-op MRI -> define largest extent of dural/bone thickening
CTV - GTV + 1cm in plane of dura, if documented brain invasion add 1cm into brain
Include all abnormal, hyperostotic bone
PTV - CTV + 3mm
What is the treatment algorithm for a low grade glioma
Maximal surgery +/- RT (50.4Gy/30#) & 6x PCV
What are the indications for upfront RT & ChT for a low grade glioma
Large initial tumour, >4cm
Incomplete resection / residual disease
>40yrs
New or worsening neurological deficit
Does vincristine need dose adjustment for renal or hepatic impairment
No renal dose adjustment
Adjusted for hepatic impairment if bili >51 or ALT/AST >60
What is the prognosis of a Gr3 oligo
5-yr OS: 30-35%
mOS 42mths with RT and PCV (oligo)
What is the prognosis of a Gr3 astro IDH mut
60-100mths
What is the prognosis of a Gr4 astro IDH mut
36mths
What is the prognosis of a GBM IDH WT, mgmt methylated
20mths
What is the prognosis of a GBM IDH WT, mgmt unmethylated
12mths
What is the prognosis of a Gr1 tumour
Curable
80% 10yr survival
What is the prognosis of a Gr2 tumour
med survival 5-10yrs
Buckner - mOS 13.3yrs with RT & PCV
What is the prognosis of a Gr4 tumour
Stupp trial (age <70yrs) - mOS 14.6 for GBM with tx
2yr OS 26%
Pts with complete resection did better, and methylated MGMT vs unmethylated
What is the prognosis of a GBM if age >70
Perry 2017 - 9.3mths with treatment (up to 12 cycles adj tmz) for all comers
If methylated - mOS 13.5mths
Most benefit in those with MGMT methylation. No statistically significant benefit for tmz if unmethylated
How is a pineoblastoma treated
NA vinc/carbo/etopo x3-4 (treat like neuroendocrine)
CSA RT
what factors should be considered when considering RT treatment of brain mets
Controlled or treatable extracranial disease
PS 0-1 (KPS ≥70)
Prognosis of at least 6mths
When should fractionated intracranial RT be considered over SRS
What dose is typically used for fractionated RT
Lesions larger 2-3cm, lesions close to a critical OAR or where V12Gy ≥10cm3 (the volume of normal tissue, excluding GTV, that receives at least 12Gy)
V12Gy of 5, 10 and >15cm3 = risk of radio necrosis of 10%, 15% and 20%
27Gy/3# or 30Gy/5#
What is the commonest primary brain tumour in adults
meningiomas, followed closely by astrocytomas
What is the commonest malignant brain tumour in adults
glioblastoma multiforme.
What is the commonest brain tumour and malignant brain tumour in children
low grade pilocytic astrocytomas
commonest malignant primary brain tumours -medulloblastomas
