Neuro Oncology, ASPHO Flashcards
1
Q
in terms of prevalence in peds haem/onc, where do brain tumours fall?
A
most common SOLID malig…second most common malig overall after leukemia
2
Q
what is the most common brain tumour overall?
A
- Astrocytomas are the most common brain tumor overall (most commonly low‐grade)
- Medulloblastomas are the most common “malignant” brain tumor
3
Q
msot common malig brain tumour?
A
medulloblastoma
4
Q
CNS tumours: prevalence in boys vs girls?
A
overall more prevalent in BOYS…1.2:1
5
Q
5 survival rate for peds CNS tumours?
A
70-75%…but misleading because some worse survival outcomes and high morbidity
6
Q
in what ways are peds brain tumours diff from adult ones?
A
histo
bio
tx
outcomes
7
Q
etiology of brain tumours generally unknown excepet in what TWO cases?
A
history of ionizing radiation…typically hx of CNS rads from past CNS tumour or CNS leukemia…..or Genetic brain tumour predisopsoition syndrome
8
Q
give 8 predisposition syndromes
A
NNTLGFRR
Nada’s Tumours: Never Let Go of Really Fresh Research
NF1, NF2, Tuberous sclerosis, Li Fraumeni, Gorlin’s syndrome= nevoid basal cell carcinoma sydnrome, Familial Adenomatous Polyposis (Gardner’s Turcot’s), Rhabdoid tumour predisposition syndrome, retinoblastoma (germline)
9
Q
Neurofibromatosis Type 1: give gene, CNS lesion, other findings
A
- NF1
- low grade glioma (optic pathway and brainstem)
- Cafe au lait spots, lisch nodules, axillary freckling
10
Q
Neurofibromatosis type 2: give gene, CNS lesion, other findings
A
- NF2
- BIlateral acoustic schwannomas, meningiomas, ependymomas
- increased risk of cataracts and seizures
11
Q
Tuberous Sclerosis: give genes, characteristic CNS lesion, other findings
A
- TSC1 and TSC2
- Subependymal giant cell astrocytoma= SEGA
- increased risk fo skin adn renal growths
12
Q
Li Fraumeni: give gene, characteristic CNS lesion, other findings
A
- TP53
- malig glioma, choroid plexus carcinoma
- nuemrous cancers at younger ages (breast, sarcoma, adrenal cortical carcinoma)
13
Q
Gorlin’s syndrome= nevoid basal cell ca syndrome…give gene, characteristic cns lesion, other findings
A
- PTCH
- medulloblastoma
- basal cell ca
14
Q
rhabdoid tumour predispositon syndrome…give gene, CNS lesion, other findings
A
- SMARCB1 and SMARCA4
- ATRT= atypical teratoid rhabdoid tumour
- rhabdoid tumours in kidney, schwannomatosis, usually <1 year at dx
15
Q
retinoblastoma (germline): give gene, charactersitic CNS lesion, other findings
A
- trilaeral Retinoblastoma (unilateral or bilateral retinoblastoma + pineoblastoma)
- pineoblastoma in these cases is usually dx’ed after the Rb but often before age of 5
16
Q
majority of brain tumours in kids are in ____ region…what fraction of tumours is this? what’s included in this region?
A
infratentorial; 2/3; cerebellum, pons, medulla
17
Q
where’s the lesion: autonomic dysfunction like temp reg, thirst, hunger affected…endocrinopathies
A
hypothalamus
18
Q
where’s the lesion? poor/loss of vision
A
occipital lobe
19
Q
where’s the lesion? decrased sense of touch/pain, poor spatial and visual perception, poor interpretation of language
A
parietal lobe
20
Q
where’s teh lesion? personality changes, decreased motor speech (Broca’s), seizures
A
frontal lobe
21
Q
where’s the lesion? ataxia, muscle movement/coordination affected, posture affected
A
cerebellum
22
Q
where’s the lesion? weakness/motor control affected, decreased consciousness, sleep/wake cycle affected
A
thalamus
23
Q
where’s teh lesion? weakness, cranial neuropathies (III-XII), autonomic dysfunction
A
brainstem
24
Q
where’s the lesion? seizures, poor memory, decreased lang comprehension (wernicke’s)
A
temporal lobe
25
4 non-localizing neuro onc symptoms?
dev delay
behavioural changes
decline in school perf
sleepiness
26
5 symptoms/signs of increased ICP?
```
headache
emesis
sleepiness/lethargy
papilledema
full/bulging fontanelle
```
27
5 endocrine sx associated with brian tumours
```
diabetes insipidus
hypoT4
wt gain or loss
panhypopit
precocious puberty
```
28
low grade gliomas include WHO grade __ and ___ ___ tumours
1;2;glial
29
name 5 LGGs
```
pilocytic astrocytoma
oligodendroglioma
ganglioma
pleomorphic xanthoastrocytoma
diffuse fibrillary astrocytoma
```
30
LGGs: what % of all brain tumours in kids?
40-50%
31
give a LGG associated with a cancer predispo
SEGA assocaited with TS!
32
how do you treat SEGA?
historically with surgery but now MTOR inhibitors are front line
33
what % of NF1 patients develop a CNS LGG?
15-20%
34
do you need to biopsy a LGG in NF1?
not if classic appearance
35
tx indication in NF1-associated LGG?
only treat if affecting vision or other neuro symptoms
36
tx NF1 associated LGG how?
chemo= first line...usually combo of carboplat and vcr or vinblastine alone
37
what do you need to AVOID in NF1 patients? (2)
radiation and alkylating chemo! high risk of secondary malig!
38
dx LGGs how?
biopsy or resection wtih goal of COMPLETE resection whenever possible...exception= NF1 pts with classic appearance of a LGG, typically within the optic pathway (dx can be made by imaging in this case)
39
other than dx'ing primary, any other eval needed for LGG?
only need additional imaging if symptoms warrant or there's a specific histo...if there's back pain, do spine MRI...also pilomyxoid astroctyoma has higher risk of mets, so do spine MRI in this case...do NOT routinely do LP for CSF cytology in LGG
40
what's the most common LGG histo?
pilocytic astrocytoma
41
pilocytic astromcytoma appears how?
low-mod cellularity, GFAP+, dense fibrillary areas...characertized by ROSENTHAL fibers!!!! =astrocytic cytoplasmic inclusions that are corkscrew shaped and eosniophililc on H and E
42
aberrations of what pathway are most common in LGG?
MAPK
43
MAPK pathway starts with FGFR...waht are teh 4 next steps?
Ras, BRAF, MEK, ERK
44
what's the most common mech of BRAF activation in LGG?
BRAF KIAA1549 fusion...in 60-80%!
45
other than BRAF fusion give another common BRAF mut in LGG
BRAFV600E...10-15% of pilocytic astrocytoma...also seen in pleomorphic xanthoastrocytoma and ganglioma
46
Tx LGG how?
try for gross total resection if possible! then observe.:)...if residual disese/no resectable: give chemo= carbo/vcr or vbl alone or combo of thioguanine, procarbazine, ccnu, vcr (PTCV)...should not give this last regimen in NF1 bc procarbazine= alkylating!...radiation effective but avoid in young kids
47
4 late effects of CNS rads?
neurocognitive changes, endocrine, ototoxicity, secondary malig
48
what types of targeted therapies are being studied in LGG?
MEK inhibitors, BRAF inhibitors
49
LGG: OS if GTR?
>90-95%
50
COG A9952: compared what? findings?
carboplatin/vcr vs TPCV in LGG...better EFS in TPCV on cure model analysis but more toxic
51
diencephalic syndrome occurs where?
diencephalon, including thalamus and hypothal
52
signs and sx of diencphalic syndrome? often caused by?
```
FTT and emaciation
abnormal eye movements and vision issues
vomiting
hydrocephalus
...oftne caused by LGG
```
53
HGG = WHO grade what?
3-4
54
HGG grade 3=?
anaplastic astrocytoma
55
HGG gr 4=?
glioblastoma multiforme
56
HGG more common in kids or adults?
adults
57
HGGs are more ___ __ __ and have much ___ ___ ___ compared to LGG
resistant to therapy; poorer survival outcomes
58
3 RFs for HGG?
- previous radiation
- Li Fraumeni syndorme
- Familial Adenomatous Polyposis = APC gene abnormality
59
dx HGG how?
biopsy/resection and path...except for DIPG!
60
goal in HGG?
GTR
61
evaluation for HGG?
- spinal MRI
| - NO need for routine LP (CSF cytology)
62
path in HGG?
```
"Path in Very Grave CNS Maligs"
highly Cellular
high Mitotic count
Vascular proliferation
Pseudopalisating necrosis
usually GFAP+
```
63
DIPG stands for?
diffuse intrinsic pontine glioma
64
dx DIPG how?
imaging alone...pons enlarged..typically doesn't enhance at dx, but this can vary
65
classic age for DIPG?
5-7 yrs
66
>80% DIPG tumours have which mutaiton?
H3 K27M
67
can you completely resect DIPG?
no
68
sx in DIPG?
CN symptoms, long tract signs, ataxia...symptoms are of SHORT DURATION (1-2 mos)
69
therapy in DIPG?
focal radiotherapy = only known beneficial tx
70
mean survival in DIPG is ___ months with almost all children____ __ ___ within ___ ___ regardless of ____
10-12; succumbing to disease; 2 years; therapy
71
what constitutes diffuse midline glioma, H3 K27 mutant?
H3 K27M seen in WHO grade 4 lesions of the midline, most commonly pons (DIPG), thalamus, or spinal cord
72
H3K27M seen in what % of DIPG?
80%
73
what other histone mutation is less common that H3K27M?
H3 G34R
74
HGG tx?
maximal safe surgical resection--> then focal radiation and chemo...although chemo not specifically agreed upon
75
For HGGs, what age range of patients have a more indolent course?
infant (most commonly <3 yrs)
76
5 year OS in HGG?
15-20%...infants slightly better
77
medulloblastoma is a highly ___ and ___ ___ ___ tumour
aggressive; rapidly growing embryonal
78
medulloblastoma located where?
cerebellum
79
what's more common: LGG or medullo?
LGG
80
medulloblastoma: more common in males or females?
males almost 2:1
81
RFs for medulloblastoma?
- Gorlin syndrome= nevoid basal cell carcinoma syndrome, due to PTCH gene mut
- Familial Adenomatous polyposis (like Gardeners' and turcot's syndrome)
82
what does medullo look like on imaging?
large heterogenous mass in posterior fossa, often with some contrast enhancement
83
Dx medullo how?
need tissue! try to get GTR!
84
what % of medullos have mets? how?
30%...through CNS
85
eval for medullo?
spine MRI AND lumbar CSF cytology
86
WHEN should you do spine MRI for medullo?
pre-op OR 10-14 days or more post-op to avoid post-op products confounding hte MRI interpretation
87
do lumbar CSF when for medullo staging?
at least 10-14 days post-op to avoid post-op products confounding interpretation
88
path in medullo?
- highly cellular
- lots of mitosis
- synaptophysin positive
89
4 histo patterns in medullo?
- classic
- desmoplastic
- extremely nodular
- anaplastic/large cell
90
what are the 4 major medullo molecular subgroups?
WNT, SHH, group 3, group 4
91
which medullo molecular subgroup has hte best prog?
WNT! 90-100% OS
92
what is ACNS1422 studying?
whether we can reduce therpay in pts with subgroup Wnt medullos
93
how do the medullo subgroups differ by age?
WNT, Group 3, and Group 4 all more common in children...while SHH more common in infants and adults
94
how do the medullo subgroups differ by histo?
- classic can be seen in all of them
- LCA common in SHH, group 3, group 4 but is RARE for Wnt
- Desmoplastic/nodular, M9EN common in SHH
95
Describe genetics in WNT medullo
Monosomy 6, nuclear beta catenin, increased risk in turcot syndrome
96
describe genetics in SHH medullo
PTCH1/SMO/SUFU, GLI2 amplification; increased risk in gorlin syndrome
97
describe genetics in group 3 medullo
i17q, MYC ampication
98
describe gneetics in group 4 medullo
CDK6 amplification, MYCN amplifcation
99
describe prog within the diff medullo subgroups
WNT: excellent
Group 3: poor
SHH: fair unless TP53 mutant...in this case, it's POOR
Group 4: fair
100
not including molecular subgroups, what = Standard risk in medullo?
age >3, GTR with <1.5 cm3 residual disease, no mets, NOT anaplastic histo
101
what are the non-molsecular risk subgroups in medullo
Standard Risk
High Risk (anything not SR except infants)
Infants (age <3)
102
how do you tx SR medullo?
-Craniospinal radiation at lower doses 2340 cGy +/- weekly vcr and boost to the PF (5400 cGy)--> then maintenance chemo
103
how do you treat HR medullo?
full dose CS radiation = 3600 cGy, +/- weekly vcr and boost to PF (5400 cGy) followed by maintenance chemo
104
how do you treat infants with medullo?
-induction chemo
-then high dose chemo
with auto stem cell rescue +/- radiation
105
for medullo, what does M0-M4 mean?
```
M0= no mets
M1= CSF lumbar cytology +
M2= mets in brain on MRI
M3= mets in spine on MRI
M4= mets outside of CNS (very rare!)
```
106
5 yrs OS in SR vs. HR. vs. infant medullo?
SR: 75-90%
HR: 40-60%
infant: 50-70%...but don't forget if you're talking about the WNT ones it's >90% at 5 yrs!
107
3rd most common brain tumour in peds?
ependymoma
108
ependyma is a ___ tumour with ___ cell ___
glial; ependymal; differentation
109
where does ependymoma occur?
usually associated with a ventricular surface but can be anywhere within the CNS....cerebellum>lateral ventrciles>spinal cord
110
RF for ependymoma?
NF2
111
dx ependymoma how?
need tissue!...aim for GTR! this is important!
112
staging for ependymoma?
-CSF cytology + spine MRI...same timing as for medullo
113
ependymoma appear how on imaging?
hetergenous mass in PF; often patchy with heterogenous enhancement
114
classic path in ependymoma?
presence of perivascular pseudorosettes
115
what molecular finding in ependymoma would yield a poor prognosis?
EPN-RELA (RELA fusion)
116
tx for ependymoma
- aim for GTR
- then FOCAL radiation 5400-5900 cGy (unless mets, then not focal...if metes, do 3600 cGy with boost to focal area fo 5400-5900 cGy)
- role of chemo= unclear
- chemo alone only if LESS THAN 1 YEAR OF AGE!
117
5 yrs OS in ependymoma?
60-80% but MANY PATIENTS HAVE LATE RELAPSES AFTER 5 YEARS:(...may eventually succumb to their disease due to recurrence
118
CSF GCTs: give 2 tumouor markers
AFP, beta HCG
119
2 major catergories of CNS GCTs?
germinoma = non-secreting, better outcome!....non-germinomatous germ cell tumour= secreting= worse otucome typically
120
CNS GCTs: more common where in the world?
Japan and other Asian countries...only 2-3% in north america, but 10-15% in Japan
121
RFs for CNS GCTs?
none known
122
how do CNS GCTs appear on imaging?
heterogenous and enhancing mass in suprasellar= pituitary region or in pineal region...sometimes both
123
symptoms of GCT in suprasellar= pituitary reigon?
Diabetes insipidus, panhypopit
124
symptoms of GCT in pineal region?
parinaud's syndrome, increaesd ICP
125
what is Parinaud's syndrome?
- paralysis of upward gaze
- pseudo-Argyll Robertson pupil (accommodative paresis and pupils become mildly dilated and show light-near dissociation)
- convergence-retraction nystagmus (on fast up-faze, the eyes pull in and the globes retract)
126
Many GCTs are ___ and can contain a ___ of ___ and other ___ __ ___ ___ elements
mixed; variety; germinoma; malig germ cell tumour
127
amongt the non-germinatomous gcts, there are many histo variants, including:
endodermal sinus tumour, yolk sac tumour, embryonal carcinoma, teratoma
128
Dx GCT how?
- Always do serum and CSF tumour markers at diagnosis
- If tumour markers in serum or CSF (AFP, beta-HCG ) are elevated enough, a dx of NGGCT can be made wtihout tissue
- if markers not diagnostic, need biopsy
- DO need full spine MRI and lumbar CSF
129
tx germinoma how?
- neoadjuvant chemo (carbo/etop x 4 cycles)
- then radiation (dose depends on response to chemo but ranges from 3000-3600 cGy and includes whole ventricle.......OR could just do radiation alone at 4000-4500 cGy but we don't really do this anymore!
130
tx non-germinatous gct how?
neoadjuvant chemo then XRT (extent and dose controversial)
131
in both germinoma and NGGCT, ___ __ ___ often advocated after ___ ___ if __ ___ remains prior to ____ to decipher ___ ___, whihc coudl be ___ ___, ___ ___, or ___
second-look surgery; neoadjuvant chemo; residual mass; radiotherapy; residual mass; scar tissue, malig tumour, teratoma...think growing teratoma syndrome= malig comonent shrinks away, but teratoma grows and need to remove iwth srugery!
132
5 yr OS for germinoma?
>90%
133
5 yr OS in NGGCT?
80-90%...subgroup though with poorer responses (less than partial responses to chemo)
134
AT/RT stands for?
atypical teratoid rhabdoid tumour
135
AT/RT is a __ ___ tumour typically seen in ___ ___ adn ___, about __ % of all pediatric CNS tumours
rare embryonal; young children; infants; 2
136
eval for AT/RT?
do need spine MRI and lumbar CSF
137
historically, prog for AT/RT is very ___ but what has helped change this?
poor; combinign chemo (auto stem cell rescue or "sarcoma-like" therapy) +/- radiation
138
immunohistochem in AT/RT?
loss of INI-1
139
Rhabdoid tumour predisopsoition syndrome is a germline mutation in ___ and ____ (___ or ___) associated with increased risk of AT/RT, other ___ tumours (commonly in ___), and _____
SMARCB1; SMARCA4; INI-1; hSNF5; rhabdoid; kidney; schwannomatosis
140
choroid plexus tumours represent ___ % of all peds brain tumours; most commonly lcoated in the ___ ___
1-2%; lateral ventricles
141
3 types of choroid plexus tumours?
choroid plexus papilloma
atypical choroid plexus papilloma
choroid plexus carcinoma
142
choroid plexus tumours usually present in ___ ___/___ with signs of ___ ___ ___
younger children/infants ;increased intracranial pressure
143
goal in choroid plexus tumours?
GTR! which is usually curative for choroid plexus papilloma specfiically
144
outcomes for choroid plexus carcinoma are___ despite a variety of multimodal therapies with __ and ___
variable; chemo; radiation
145
choroid plexus carcinoma OS at 5 yrs?
20-50%
146
RF for choroid plexus carcinoma?
Li Fraumeni
147
craniopharyngioma is a rare __ tumour thought to be due to ____ origin
epithelial; maldevelopmental
148
craniopharyngioma represents ___ % of all peds brain tumours
6-9%
149
how does crainopharyngioma present?
headaches, emesis, visual field cut, endocrionpathies
150
most common location for craniopharyngioma?
suprasellar/pituitary
151
imaging of craniopharyngioma looks like?
mixed solid and cystic mass at the suprasellar region
152
path of craniopharyngioma?
squamous epithelium lining cystic cavities, often containing calcium and keratin
153
tx for craniopharyngioma?
GTR!..if can't do or diseases progresses, do focal rads
154
although PFS and OS are ___ for craniopharyngioma, many pts have numerous ___ affecting __ __ __ (eg: 4?)
good; co-morbidiites; quality of life; endocrionpathies, behavioural issues; visual dysfunction; seziures...but actually considered "benign low grade tumour"
155
after CNS radiation, inreased risk of what seocnary brain tumours most commonly?
HGG, meningioma
156
secondary brain tumours after rads usually occur when?
7-10 yrs after radiation
157
risk of secondary brain tumour after radiation?
=5%
158
give 4 late effects of CNS radiation
```
neurocognitive decline
ototoxicity
endocrine dysfunction(hypothyroidism, GH def, delayed puberty)
secondary malig
cerebrovascular events
```
159
late effect of cyclophos?
infertility
160
late effect of cisplatin?
ototoxicity
161
late effect of etop?
secondary malig
162
late effect of IT mtx?
leukoencephalopathy
163
late effect of doxo?
cardiac dysfunction
