CNS adult and peds

Question 1

NF type 1 or von Recklinghausen’s disease. what CNS tumor association?
meningioma, astrocytoma or GBM or LGG?

Answer 1

astrocytoma!. pilocytic most common.

Question 2

NF type 2, what intracranial tumor most common?

Answer 2

Schwannomas, most often b/l acoustic neuromas are more common than meningioma or astrocytomas.

Question 3

what are the negative risk factors for scoring LGG per Pignatti?

Answer 3

Age greater than 40, astrocytoma subtype, tumor larger than 6cm, tumor crossing midline, presence of neurolgoical deficit prior to surgery. 2+ factors is low risk group with MS of 7.7yrs , whereas 3 or more is high risk with MS of 3 years.

Question 4

EORTC 22844, Believer’s Trial in LGG showed what?

Answer 4

LGG randomized to immediate PORT with 45 or 59.4Gy. 25% had GTR. dose escalation did not improve OS, PFS.

Question 5

Dose max to cochlea and pituitary?

Answer 5

Max 36. stnd fx. srs dose to chiasm is 8-10Gy

Question 6

what does MGMT do?

Answer 6

it is a DNA repair enzyme that repairs damage induced by alkylating agents, such as TMZ. those with methylated MGMT were found to have improved OS with RT and TMZ.

Question 7

EORTC 22845, “Non Believers” Trial showed what?

Answer 7

LGG randomized to early vs delayed RT. PFS imrpoved in early RT (5.3 vs 3.4yrs) but no difference in OS (7yrs). But better seizure control in early RT (25 vs 41%) Median dose was 54Gy.

Question 8

EORTC 26951, LGG pts randomized after surgery and RT +/- chemotherapy. what did it show?

Answer 8

AO’s after surgery and RT to either obs vs adj pCV (procarbazine, lomustine, vincristine). 5yr results lin 2006 showed PFS only (1.9 vs 1.1yrs). 1p19q deletion had 5yr OS of 74 vs 30%. in 12 yr f/u, PCV improved PFS and OS. MS 42 vs 31 mos. those with the deletion did not reach median survival yet at 12 yrs.

Question 9

what evidence do we have that 60Gy is the max dose for HGG? What evidence is there that young people have better prognosis in HGG?

Answer 9

ECOG/RTOG trial from 1983 looking at stnd 60Gy WBRT+10Gy bst, 60Gy+BCNU, 60Gy WBRT+CCNU+DTIC vs 60Gy alone. Age was most pronstoic with better survival in <40yrs. BCNU did nto improve survival compared to 60Gy WBRT Alone. CCNU+DTIC was more thrombocytopenic than BCNU.

Question 10

per RTOG 90 05, what is the SRS dose in brain mets and gliomas?
<2cm, 2-3cm, 3-4cm?

Answer 10

<2cm (24Gy)
2-3cm (18Gy)
3-4cm (15Gy)
48% fail locally, but most o fthose are gliomas than mets that fail locally.

Question 11

how is TMZ given

Answer 11

with GBM, given minutes before RT at dose of 75mg/m2, then adjuvantly at 150-200mg/m2 x 6 cycles.
the OS benefit at 5yrs was 10% vs 2%.
initial report in 2005 at 2yrs showed MS of 14.6 vs 12 mos. 2yrOS was 27% vs 11%.
MGMT status is te strongest predictor of outcome.

Question 12

Bauman elderly GBM trial showed what MS with RT vs best supportive care?

Answer 12

=>60yrs and KPS=<50 got 30/10fx, MS imrpoved from 1 vs 10mos.

Question 13

Roa, elderly GBM trial with hypofx RT for poor prognosis pts showed what?

Answer 13

60/30fx vs 40/15fx. same OS, MS (5mos).

30fx less likely to finish RT (74% vs 90%) and also needed an increased in steroids post tx.

Question 14

what was teh RT dose in the elderly GBM study by Keime-Guibert?

Answer 14

=>70, KPS =>70 got best supportive care or 50.8/28fx. the MS was prolonged at 29 vs 17 wks, w/o RT. QoL did not differ.

Question 15

what pathologic association with meningiomas?

Answer 15

psammoma bodies = meningioma
rosenthal fibers = astrocytomas
psuedorosettes = ependymoma
Homer-Wright rosettes = medulloblastoma

Question 16

per Goldsmith, what is the 5yr PFS for meningiomas after GTR? STR? PORT in STR? PORT for malignant meningioma? using 54Gy

Answer 16

GTR 5yr PFS: 89%
STR PFS = 50%
PORT in STR = >85%
PORT in malingant RT  = 40-50%
outcomes are much worse when dose <52Gy

Question 17

for ependymoma, is GTR more common in supratentorial or infratentorial? LF vs DF? RT dose?

Answer 17

GTR more commonly achieved in supratentorial. resection extent is the most important predictor of outcome. LR is most common, therefore dose is 59.4Gy.

Question 18

RTOG 94-02 looked at oligos with PORT with 59.4Gy +/- PCV chemo. what were the outcomes?

Answer 18

pts got either PORT alone or 4cycles of PCV followed by PORT. PFS was better wtih PCV, 2.6 vs 1.7yrs. but more toxicity with PCV. On FISH, 1p19q deletion had MS >7yrs and better PFS. On 11.yr f/u update, MS of the codeleted pts was 14.7yrs with PCV vs 7yrs without PCV.

Question 19

how many mitoses per 10 HPF makes anaplastic meningioma?

Answer 19

20.

Question 20

What are the 4 Simpson grading systems?

Answer 20

I: GTR, bone and dura
II: GTR, coagulation of dural attachment
III: GTR, with intact dura
IV: STR.
Kadish staging is used for estesioneuroblastoma btw.

Question 21

what does the neurohypophysis secret?

Answer 21

the posterior lobe of the pituitary or neurohypophysis, secretes ADH and oxytocin.
the anterior lobe or adenohypophysis, secretes, prolactin, TSH, GH, LH, FSH, ACTH.

Question 22

what is the order that the hypothalamic pituitary axis hormones are affected from RT?

Answer 22

GH, ACTH, LH/FSH, TSH (Merchant. Early neuro-otologic effects…IJROBP, 2004)

Question 23

what are the contents of the cavernous sinus?

Answer 23

III, IV, VI then V1 and V2.

Question 24

what is the COMS classification? collaborative ocular melanoma study

Answer 24

small= 1-3mm thick and 8mm thick and >16mm dimension

Question 25

acoustic neuromas are seen in which NF type?

Answer 25

NF type 2. affects vestibular division of Cn VIII

Question 26

what is the RT dose for standard risk medulloblastoma? what is standard risk medulloblastoma?

Answer 26

stnd risk medullo: >3yo, GTR/NTR <1.5cm2 residual, M0. so older age, no bulky disease adn no mets.
RT dose is 23.4 Gy CSI, then boost to 54 with weekly vincristine (adj cis/CCNU/vincristinex8).
POG 8631 compared 36 vs 23.4Gy CSI, high relapse with 23.4. BUT
CCG-9892 showed that 36Gy = 23.4 Gy + vincristine and adj chemo.
if high risk medullo, CSI = 36Gy.

Question 27

St Jude ran a trial to try to reduce the RT volume to reduce neurocog effects. What was the dose and chemo used and PF failure rate?

Answer 27

stnd risk medullo, got 23.4Gy with 36Gy PF bst and tumor bed bst to 55.8 Gy. chemo was 4c Cyclo/cis/vincristine adj. 3yr PF failure rate was 6.3%. there was a signfiicant reduction in RT dose to PF getting >55Gy. temporal loves, cochlea and hypothalamus were * lowered.

Question 28

baby POG showed what?

<3yo)

Answer 28

PFS after cyclo/vincristine and cis/etop was 32%. not great, therefore, COG P9934 chose young kids <3yo got 16wks chemo after surgery, then second look surgery, and RT to PF. the addition of CRT imrpoved EFS to 50%.

Question 29

in ependymoma do you do a maximal total resection? even if it causes neurologic deficit?

Answer 29

yes. also you still give 59.4Gy after surgery even for GTR. due to high LR.

Question 30

young child has a GTR for low grade astrocytoma in cerebellum waht is the next step?

Answer 30

observaton. Per CCG/POG 9130, 5yr LC is 92%.

Question 31

do germinomas require bx? what si the RT field for them?

Answer 31

yes germinoma requires biopsy, tx WVRT. ACNS 0232 randomized to whole ventricular RT to 24Gy with 21Gy bst if prsented with DI or mets vs preRT chemo followed by response based RT. if CR or MRD, 30 to IFRT only. if M+, then 21Gy CSI with 9Gy bst to prechemo volume. this trial closed due to poor accrural, therefore WVRT is stil lthe standard.

Question 32

where do craniopharyngiomas originate?

Answer 32

embryonic remnant of the anterior pituitary (rathke’s pouch) bimodal occurence in peds and 55s. lots of endocrine abn, and presents with cystic/solid components.

Question 33

what is the general maangement of craniopharyngiomas?

Answer 33

limited resection followed by upfront RT-only 1 IQ pts lost compared to radical surgery, 10 IQ pts lost. on MVA dose >55Gy was sgnfiicnatly related wtih LC and that pretx hypopituitarism predicted for tx copmlication probability.

Question 34

what is the best mgmt for asx optic glioma in peds?

Answer 34

close observation
at progression, surgery if inoperable, chemo
NF1 responds the same, but kids <5yrs had a better PFS, nearly double at 74%.

Question 35

what is the AT/RT gene mutation seen in 80%?

Answer 35

INI-1, this distinguishes AT/RT vs choroid plexus carcinoma