[ROQs] CNS Flashcards
(187 cards)
1
Q
What were the outcomes of the Stupp trial (2009) for GBM?
A
- GBM → 🏆 60 Gy + conc and adj. TMZ vs. 60 Gy alone
- ↑ Median OS 14.6 mos vs. 12.1 mos
- ↑ 2-yr OS 27% vs. 11%.
- ↑ 5-yr OS 10% vs. 2%
- Methylated MGMT (clear benefit):
– Median OS 22 mos TMZ vs. 15 mos
– 2-yr OS 46% vs. 23%
– 5-yr OS 14% vs. 5% - Unmethylated MGMT (trend to benefit):
– Median OS 12.7 vs. 11.8 mos (p=0.06)
– 2-yr OS 14% vs. 2%
– 5-yr OS 8% vs. 0
2
Q
What were the extent of resection (CTR vs. STR vs. bx) and outcomes for pts who underwent bx only in the Stupp trial (2009) for GBM?
A
The extent of resection in Stupp trial:
- GTR: 40%
- STR: 45%
- Bx: 16%
For bx only:
- RT vs. RT/TMZ + TMZ
- 7.8 vs. 9.4 mos (NS)
3
Q
What were the findings of the RTOG 9402 trial?
A
- Anaplastic oligodendrogliomas tumors after surgery → Neoadj PCV x 4C f/b RT vs. RT alone
- 1p19q codeleted tumors
– ↑ Median OS: 14.7 vs. 7.3 yrs (SS) - Non-codeleted tumors
- ~ Median OS 2.6 vs. 2.7 (NS)
- Entire cohort:
– ~ Median OS: 4.6 vs. 4.7 yrs (NS)
The trial is essential for highlighting the improved prognosis of 1p19q codel in oligodendrogliomas.
MNEMONIC: 9402 is the baby sister of 9802.
4
Q
What were the findings of the RTOG 9802 trial for LGG?
A
- LGG
– High risk (Age ≥ 40, STR) →🏆 54 Gy RT f/b adj. PCV x6 vs. 54 Gy RT alone
– Low risk (Age < 40. GTR) → observation - Results: PCV vs. no PCV
– ↑ Median OS 13.3 vs. 7.8 yrs
– ↑ 5-yr OS 72% vs. 63%
– ↑ 10-yr OS 60% vs. 40%
– ↑ Median PFS 10.4 vs. 4.0 yrs
– ↑ 10-yr PFS 51% vs. 21% - On subanalysis, benefit only in IDH-mut (non-deleted or codeleted). There is no benefit to chemo in IDH-wt
- Median OS by histology:
– IDHmut/codel: not reached vs. 13.9 yrs
– IDHmut/noncodel: 11.4 yrs vs. 4.3
– IDHwt: 0.7-1.9 yrs (NS)
MNEMONIC: 9802 comes before 2005 (Stupp): LGG before HGG
5
Q
What were the findings of the EORTC 26951 (van den Bent at al. JCO ‘13)?
A
Anaplastic oligodendroglial tumors s/p surgery → RT (59.5 Gy) f/b PCV x 6C vs. RT alone
- ↑ median OS 3.5 vs. 2.5 yrs (SS)
- Subgroup analysis: Codel vs. non-codel (1p19q)
– PFS SS w/ addition of PCV
– Improved OS trend but not NS - RT Regimen:
– 45 Gy to an initial volume (+2.5 cm) f/b 14.4 Gy boost (+1.5 cm): 59.4 Gy total - MEMORY HOOK: Kinda like 9402!
6
Q
Per EORTC 26951, what factors are a/w improved prognosis (PFS and OS) in oligodendroglial tumors?
A
- MGMT promoter methylation
- Surgery (rather than biopsy alone)
- 1p19q co-deletion
- lack of tumor necrosis
7
Q
What were the findings of the CATNON trial?
A
1p19q non-codeleted anaplastic gliomas (astrocytomas) randomized (1:1:1:1) to RT alone vs. RT + adj. TMZ vs. RT + con TMZ vs. RT + adj/con TMZ (adj for 12 mos)
- Adj. TMZ vs. no Adj. TMZ
– Median OS: 7 yrs vs. 4 yrs (SS) - Conc TMZ vs. no conc. TMZ
– Median OS: 5.6 yrs vs. 5 yrs (NS)
HOOK: concurrent and adjuvant TMZ in non coded tumors
8
Q
What is the CODEL trial investigating?
A
1p19q codeleted gliomas, randomized to:
- RT alone
- RT + adj. PCV
- RT + adj/con TMZ
9
Q
What were the recommended RT doses for the RTOG 0539 trial for meningiomas?
A
NB: PTV for high risk is actually CTV
10
Q
What were the findings of the NOA 04 trial?
A
Upfront RT vs. CHT after resection for gliomas
- Anaplastic glioma s/p resection → RT (switch to CHT (PCV/TMZ) at progression) vs. CHT (switch to RT at progression)
– No sig. difference
– Median TTF ~4.5 yrs, PFS ~2.6 yrs, OS 8 yrs vs. 6.5 yrs (NS)
MNEMONIC: Noa → No RT (technically not correct since CHT arm switched to RT at progression)
11
Q
What were the findings of the RTOG 0539 trial for meningiomas?
A
- Low-risk: Gr I s/p GTR or STR
– 5-yr PFS: 86%
– 5-yr LC: 88%
– 5-yr OS: 98% - Intermediate-risk: recurrent Gr I, Gr II s/p GTR → 54/30
– 3-yr PFS: 94%
– 3-yr LC: 96%
– 3-yr OS: 96% - High-risk: Gr II s/p STR, recurrent Gr Il, any Gr III → 60/30
– 3-yr PFS: 59%
– 3-yr LC: 69%
– 3-yr OS: 79%
– (Hook: 60, 70, 80)
12
Q
What were the findings of the RTOG 0424 trial for high-risk LGG?
A
- LGG with ≥3 risk factors (SATAN) → 54 Gy + conc and adj TMZ
– 3-yr OS 74% [vs. historical control 54%]
– 5-yr OS 61%
– 10-yr OS 35%
– Median OS 8.2 yrs
– 3/5/10-yr PFS 59/47/26%
– Median PFS 4.5 yrs
13
Q
What was the 5-year risk of progression for LGG s/p GTR in a < 40-year-old pt per the findings of the RTOG 9802?
A
~ 50%
14
Q
What defines a malignant meningioma?
A
≥20 mitoses per 10 high power fields and/or 1 of the following
– Homozygous deletion of CDKN2A/B
– TERT promoter mutation
– Frank anaplasia
15
Q
What defines an atypical meningioma?
A
- ≥4 but <20 mitoses per 10 high power field
- Brain invasion
- Clear cell/choroid histology,
- or ≥ 3 of the following:
– Increased cellularity
– Prominent nucleoli
– Sheet-like or patternless growth
– Foci of spontaneous or geographic necrosis
– Small cells with a high nuclear/cytoplasm ratio
16
Q
Which medications can be used for GH-secreting pituitary adenoma causing acromegaly?
A
- Somatostatin (GH inhibitor): Ocreotide, lanreotide
- Carbegoline (dopamine agonist), for pts refractory to somatostatin
17
Q
How does the hypothalamus shut down the production of prolactin from the pituitary gland?
A
By secreting dopamine
18
Q
What post-op RT dose is recommended for hemangiopericytomas s/p GTR?
A
- 50 - 60 Gy
- Improves LC
19
Q
What are the long-term control rates for non-secretory vs. secretory pituitary adenomas post-surgery/RT/both?
A
- non-secretory: 10-yr PFS 90%
- secretory: 10-yr PFS 66%
20
Q
What is the longterm risk of AVM bleeding in a pt and what are the risks of death and neurologic deficits at first bleed?
A
- Lifetime Risk = 105 - age in yrs
- Risk of death at 1st bleed: 10%
- Risk of neuro deficits at 1st bleed: 50%
21
Q
What % of NF-1 pts develop optic pathway gliomas?
A
25%
22
Q
What is the risk of facial numbness from SRS for trigeminal neuralgia?
A
3-15%
23
Q
What are the RT and SRS doses for non-secretory and secretory pituitary adenomas?
A
- non-secretory: 45 Gy (12-20 Gy)
- Secretory: 45-50.4 Gy (15-30 Gy)
– TH-secreting: 54 Gy
24
Q
What are the MRI characteristics of benign meningiomas?
A
- T1w/o contrast x: isointense
- T1 post-contrast: uniformly contrast enhancing
- T2: iso/hyperintense
25
What is the NCCN dose range for LGG?
45-54 Gy
26
What are the findings of RTOG 0825?
- GBM → SOC (Stupp) + Bev vs. SOC + Placebo
-- ~OS: 15.7 vs. 16.1 mos
-- ↑ PFS w/ bev: 10.7 vs. 7.3 mos
-- Adverse effects higher in the bev group: hypertension, thromboembolism, intestinal perf, neutropenia, a decline in QOL and cognitive function
27
What are the "per protocol" PTV coverage goals for RTOG 0825?
- 95% PTV covered by 60 Gy
- 99% PTV covered by 54 Gy
28
What is the first-line therapy for **non-secretory** pituitary adenomas?
trans-sphenoidal surgery
29
When is RT indicated for pituitary adenomas?
Unresectable/residual disease
30
What is the first-line therapy for **secretory** pituitary adenomas?
Medical management
31
When and which medical management is used for pituitary adenomas (PAs)?
- Manage sx from secretory PAs
-- Prolactinoma → Carbegoline or bromocriptine
-- GH-secreting PA → somatostatin
-- ACTH- secreting PA → ketoconazole
32
How long do ACTH levels take to normalize after RT for pituitary adenomas?
1-2 yrs
33
What is the first-line therapy for prolactinomas?
- Carbegoline or bromocriptine
-- Highly effective: Can normalize serum prolactin levels in 80-90% of pts
34
What were the findings of RTOG 9305 for GBM?
- GBM s/p resection → ± SRS (15-34 Gy) → EBRT (60 Gy) w/ BCNU
-- Median OS 13.5 vs. 13.6 mos
35
What were the findings of CeTeG/NOA-09 for GBM?
- GBM s/p resection → EBRT-TMZ vs. EBRT TMZ/Lomustine (CCNU) x 6C
-- CCNU (100 mg, Day 1), TMZ (150-200 mg, Day 2-6) q6weeks x 6C
-- ↑ median OS: 31.4 → 48.1 mos (↑ 16 mo)
36
What were the results of the Roa et al. trial (JCO 2004) for standard vs. hypofx RT for elderly pts (≥ 60 yrs, KPS ≥ 50) w/ GBM?
- Standard (60/30) vs. Hypofrac (40/15), both w/ conc. and adj. TMZ
-- OS: 5.1 vs. 5.6 mos (NS)
-- Need for ↑ post-tx steroid dose: ~50% vs. 25% (SS)
MNEMONIC: **R**oa reduces **R**T
37
What was the def of "old and frail" per the 2nd Roa et al. trial (JCO 2015) comparing two hypofx RT regimen in this pt population?
- Frail: Age ≥ 50 & KPS 50-70
- Old and frail: Age ≥ 65 & KPS 50-70
- Old: Age ≥ 65 & KPS 80-100
This is in contrast to his earlier paper, which used ≥ 60 yrs and/or KPS ≥ 50 for inclusion
38
What were the outcomes of the 2nd Roa et al. trial (JCO 2015) comparing two hypofx RT regimens in the old and/or frail pt population?
- 20 Gy / 5 fx vs. 40 Gy / 15 fx → TLD: NS
-- Median OS: 7.9 vs. 6.4 mos (NS)
-- Median PFS: 4.2 mos for both (NS)
-- Similar QOL at 4 and 8 weeks (NS)
MNEMONIC: **R**oa reduces **R**T
39
What are the typical SRS doses fo→AVM?
- Depends on size (Rx to the edge of AVM, No CTV or PTV)
-- < 3 cm → 21-24 Gy
-- > 3 cm → 16-18 Gy
-- Close to brainstem: < 16 Gy
40
Do you hold anti-secretory medications when treating secretory pituitary adenoma?
Yes, cuz it was thought that the efficacy of tx is decreased if the pt is taking anti-secretory meds
41
What is the median OS by glioma type?
42
How are the different meningioma grades defined?
43
What were the findings of the EF-14 trial (Stupp et al, 2015, updated 2017)?
GBM → RT + conc TMZ f/b one of (2:1 randomization)
(a) 🏆 TTFields + adj. TMZ
(b) adj. TMZ:
Outcomes
- ↑ Median PFS: 6.7 vs. 4.0 mos (SS)
- ↑ Median OS: 20.9 vs. 16.0 mos (SS)
- ↑ 2-yr OS: 43% vs. 31% (SS)
- ↑ 5-yr OS: 13% vs. 5% (SS)
44
What are the main criticisms of the EF-14 clinical trial?
1. Open-label study (Not double-blinded and thus without a placebo-control arm.)
2. Randomization occurred after the completion of chemoradiotherapy.
3. Increased support for TTF patients (related to the device).
4. Financial support to many of the study investigators
45
What are the dose recommendations for a chordoma?
- ≥ 70 Gy (a/w ↑ OS; not achievable using photons)
- Thus, protons or heavy ions are recommended
- Protons are also a/w ↑ survival @ 5 yrs: 100% vs. 34%
46
What are the V10 and V12 thresholds beyond which SRT as opposed to SRS should be considered?
- Rule of 20s
-- V12Gy > 8 cc
-- V10Gy > 10 cc
- Minimized risk of radionecrosis
47
What is the average growth rate of a meningioma?
2-4 mm per yr
48
What is gliomatosis cerebri?
When a glioma involves ≥ 3 cerebral lobes
49
What's the order of hormones affected by RT for pituitary adenomas?
- Go Look For The Adenomas, Please
-- GH
-- LH/FSH
-- TSH/ACTH
-- Prolactin
50
What is the most common secretory pituitary adenoma?
Prolactinoma (45%)
51
What % of pituitary adenomas are secretory?
45-75%
52
What are the cure rates for secretory pituitary adenoma w/ RT only?
Cure rates:
- **GH secreting; 60-100%**
- ACTH secreting: 50-100%
- TSH normalizes in 2/3 rd (67%)
- Prolactinomas: 25-50%
-- Thus, med management is the first line!
53
What is the incidence of radionecrosis following RT alone in pts w/ GBM?
3-yr incidence of radionecrosis: 13%
54
What are the findings of the QUARTZ study?
Quality of life after treatment for brain metastases:
- NSCLC w/ brain metastasis unsuitable for surgery or SRS
-- Noninferiority: WBRT 20 Gy/5 fx w/ supportive care (SC: Dex) vs. SC alone
--- QALYs noninferior (NS)
--- Median OS ~2 mos (NS)
--- No difference in QOL or dex use (NS)
-- On subanalysis: ≥5 mets or < 60 YO → OS benefit from WBRT
-- There was some trend to OS benefit if primary controlled, no extracranial mets, or higher GPA
55
What is the difference b/w Broca and Wernicke's aphasia?
B**r**oca → f**r**ontal lobe of the dom hemisphere
W**e**rnicke → t**e**mporal lobe of the dom hemisphere
56
What were the findings of the Flickinger trial (IJROBP 2001) comparing single vs. two isocenter techniques for treating trigeminal neuralgia?
The two isocenter treatments effectively increased the length of the trigeminal nerve being treated.
-- Pain relief was eq
-- 2 isocenter arm had higher tox
-- Con: ↑ treated nerve length does not improve response and may increase toxicity
57
What is the management paradigm for spinal cord tumors?
- surgical ± risk-adapted RT
-- Intradural-extramedullary tumors (meningiomas and nerve sheath tumors), maximum surgical resection with preservation of neurological function is the goal.
-- intramedullary tumors (ependymomas and astrocytomas) complete surgical resection remains a challenge but is ideal if it can be accomplished with preservation of neurological function.
-- Patients are then considered for radiation therapy based on histology, tumor grade, extent of resection, and nature of resection (en bloc vs. piecemeal).
58
What were the max tolerated dose ranges in RTOG 9005?
Trial investigating max tolerated doses for SRS in patients w/ recurrent primary (36%) and metastatic (64%) tumors after prior WBRT (30-60 Gy)
Doses:
- ≤ 2 0 mm → 24 Gy
- 21-30 mm →18 Gy
- 31-40 mm → 15 Gy
Outcomes (radionecrosis):
- 6 mos → 5%
- 12 mos → 8%
- 18 mos → 9%
- **24 most → 11%**
59
What post-op SRS doses can be used for resected brain mets?
Zindler, Jaap & Bruynzeel, Anna & Eekers, Danielle & Hurkmans, Coen & Swinnen, Ans & Lambin, Philippe. (2017). Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain metastases: A phase III randomised multicentre trial. BMC Cancer. 17. 500. 10.1186/s12885-017-3494-z.
60
What are the Pignatti criteria (JCO 2002) and what do they represent?
Prognostic factors for survival in **low-G gliomas (LGG)**
- SATAN:
-- Size ≥ 6 cm
-- Age > 40 YO
-- Tumor crossing midline
-- Astrocytoma histology
-- Neurologic deficits preop
61
What were the results of the believers' trial for low-grade gliomas?
- WHO I-II s/p surgery
-- 🏆 45 Gy vs. 59.4 Gy
-- No difference in PFS (49%) or OS (59%)
62
What were the results of the non-believers' trial (EORTC 22845) for low-grade gliomas?
WHO I-II s/p surgery (any kind)
-🏆 54 Gy vs. obs (RT allowed at recurrence)
-- 1-yr seizures: 25% vs. 41% (SS)
-- 5-yr PFS: 55% vsme. 35% (SS)
-- Median PFS 5.3 yrs vs. 3.4 yrs (SS)
-- 5-yr OS: 66-68% (NS)
-- Median OS ~7.3 yrs (NS)
-- Rate of malignant transformation 72% vs. 66% (NS)
-- No changes in cognitive deficits after treatment
63
Does adjuvant RT increase the risk of malignant transformation of gliomas at the time of recurrence?
- No!
- Per non-believers trial:
-- Rate of malignant transformation RT vs. obs: 72% vs. 66% (NS)
64
In what cardinal direction do pituitary adenomas typically grow?
- Superiorly
- They can't grow inferiorly because of sella turcica
65
What is the anatomic location of the hippocampus?
- Within the temporal lobe
- Medial to the temporal horn of the lateral ventricle.
66
What is the usual SRS dose for acoustic neuromas?
12-13 Gy
- γ knife: R<. ub>x to the 50% IDL
- LINAC: Rx to the 80% IDL
67
What are the categories of adult gliomas per WHO 2021 classification?
1. Astrocytoma, IDH-mutant
2. Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted
3. Glioblastoma, IDH-wildtype
68
What are the precursor cells for meningiomas?
Arachnoid cap cells (found in arachnoid villi)
69
What are the precursor cells for ependymomas?
Ependymal cells lining the ventricles and the CSF system
70
What are the precursor cells for oligodendrogliomas?
Oligodendrocytes
71
What are the precursor cells for schwannomas?
Schwann cells
72
What are the characteristics of true vs. pseudoprogression?
In true progression:
- MR spectroscopy: ↑ choline from ↑ cell membrane turnover in rapidly growing tumors
- Perfusion MRI: ↑ relative cerebral blood volume (rCBV) due to increased microvascular density
- Diffusion-weighted imaging: ↓ water motion due to the rapidly growing tissues
73
What is the rate of pseudoprogression in GBM patients treated w/ RT and TMZ?
- 20-30%n (Brandes et al JCO 08)
- Upto 90% in MGMT methylated tumors
74
What are the CNS dose constraints per RTOG 0825?
- Lenses V7 ≤ 0.03 cc
- Retinae V50 ≤ 0.03 cc
- Optic nerve V55 ≤ 0.03 cc
- Optic chiasm V56 ≤ 0.03 cc
- Brainstem V60 ≤ 0.03 cc
75
What are the SRS constraints for the Optic system to keep the risk of radiation-induced optic neuritis rare?
Optic Nerve/Chiasm: Dmax < 8 Gy
- Risk of damage is rare
Risks at different doses:
- 8 Gy → 0-2.6%
- 10 Gy → 0-4.7%
- 12 Gy → 0-13.9%
76
For CSI using two spinal fields (SF1 & SF2; Cord Length > 40 cm), at what vertebral level should the two fields be feathered? How often?
- Where: L2
- How much: 5-10 mm
- How often: Weekly (q 9 Gy)
77
How should cavernous sinus meningiomas be managed?
RT alone, since they have a very high surgical morbidity risk
SRS can be done if they are ≥ 2 mm from the optic pathway
78
What are the predictors of slow progression for meningiomas?
- Hypointense on T1 PC
- Calcifications
- Elderly patient
- No growth on serial scans
79
What is the standard SRS dose for a meningioma?
- 12-16 Gy
- Exact dose based on surrounding OARs
80
What is the risk of permanent neurologic deficit after an AVM bleed?
~50%
81
Which pituitary hormones are unaffected by RT for pituitary adenomas?
- Vasopressin (hence, Diabetes insipidus is not a common side of RT
- Oxytocin
82
What lab and imaging studies are required for the staging of ependymomas?
- CSF studies
- MR bone/spine
83
What is the age of presentation for ependymomas in adults?
3rd or 4th decade of life
84
What is the general treatment paradigm for ependymomas?
- Surgical resection
- Adjuvant RT, even after GTR
-- RT to pre-surgical tumor volume + 1-2 cm: 54-59.4 Gy
-- Only CSF+ tumors receive CSI: 30.6-36 Gy f/b boost to 54-59.4 Gy (confirm this)
85
What are the 10-year LC and OS for ependymomas after treatment?
86
Can you omit RT for ependymomas after GTR?
- In most cases, no
- Rarely: for G II ependymomas s/p GTR, observation can be considered
87
Is observation appropriate for ependymomas?
- This is controversial
- Rarely: for G II ependymomas s/p GTR, observation may be appropriate
88
Identify the labeled structure.
- Choroid plexus, often calcified in adult
- Produces CSF
89
What is the WHO grading for meningiomas?
90
What is the prevalence of different grades of meningiomas?
91
What is the 5 Y OS for G II gliomas?
60-70%
92
Which vestibular schwannomas should be managed w/ initial surgery?
- A tumor causing any neurologic sx: surgery → adjuvant RT
- Tumors > 3.5 cm causing hydrocephalus: shunting → surgery → adjuvant RT
93
What is the preferred time for post-op SRS for resected brain mets?
**≤ 4 wks**
- Time to SRS is predictive of LC (outcomes), ROTH, PRO '21
-- ≤ 4 weeks: LC 2.3%
-- > 4 weeks: LC 23.6%
-- Similar OS
94
Describe the ventricular system of the brain?
95
What are the anatomic parts of the brainstem?
96
What are the risk factors for the development of meningiomas?
Risk Factors:
- Prior RT (at 20 yrs)
- NF-2
-- Merlin is defective in NF-2 and also susceptible to bilat ACN/ependymomas and juvenile subcapsular cataracts.
- HRT in women (RR 2). Estrogen/progesterone are controversial.
--70% of meningiomas express progesterone, but trials with hormone manipulation have not proven effective.
97
What visual field deficits are a/w various optic pathway defects?
98
What are the rates of recurrence for solitary fibrous tumors (hemangiopericytoma)?
Risk of recurrence:
- 1 yr: 3.5%
- 5 yr: 46%
- 10 yr: 92%
- Rate of extraneural mets: 26%
Recurrence risk decreased to 1/3 w/ PORT (SS)
99
What is the classic pathologic finding of ependymomas?
Perivascular Pseudorosettes
100
Where do ependymomas typically occur?
- Adults: Spine (75%)
- Children: Posterior fossa (60%)
-- Median age 4-5 yrs
101
What is the risk of radiation myelitis w/ a spinal cord dose of conv RT 54 Gy, conv RT 61 Gy, SRS 13 Gy, and SRT 20 Gy in 3 fx?
Radiation Myelitis risk, per QUANTEC
- Conv. 54 Gy, SRS 13 Gy, SRT 20 Gy in 3 fx → <1%
- Conv. 61 Gy → <10%
102
What are the outcomes of the ARUBA trial?
Unruptured AVM (Characteristics: Spetzler-Martin grade I-III in ~30% each, and grade IV in ~10%)
- 🏆 med management vs. med management + intervention (SRS, embolization, NSGY, or combination)
--Mean f/u of 50 mos
-- Death or stroke 3.39 vs. 12.32 per 100 pt-years
-- Deaths: n=2 vs. 4
-- Adverse events 59% vs. 79%
Outcome by intervention:
- Neurosurgery in 21%. 95% of these had eradication, 41% had an event
- SRS in 54%. 21% had eradication, 37% had an event
- Embolization in 62%. 52% had eradication, 50% had an event
103
What is the obliteration rate and the risk of hemorrhage of AVM post-radiation treatment?
5 yr obliteration rate: 91%
Risk of hemorrhage compared to pre-SRS risk:
- Latency period (2-3 yrs): ↓ 50% (abs risk <5%)
- After obliteration: ↓ 90%
- Risk of hemorrhage persists but is significantly reduced after obliteration
104
What is the risk of hemorrhage from untreated AVMs per year?
- unruptured: 1-3%
- risk increased after a prior rupture
105
What is the Spetzler-Martin scale for grading AVMs?
106
What are the rates of hearing preservation in acoustic neuroma patients treated w/ GK SRS vs. surgery?
GK SRS:
- Hearing preservation: 70% vs. 37.5%
- Facial nerve tox: 0% vs. 37%
107
What are the rates of vertebral compression fractures for spine SBRT for different dose/fx and overall (Sahgal et al. JCO 2013)?
Dose/fx:
- ≤ 19 Gy → 10%
- 20-23 Gy → 20%
- ≥ 24 Gy → 40%
Overall: 14%
-- Median time to fracture 2.46 mos
-- 65% fractures occur in the first 4 mos
108
What are the risk factors for vertebral compression fractures following SBRT?
- ≥ 20 Gy / fx
- baseline VCF
- a lytic tumor
- spinal deformity/misalignment
109
Do dose escalation > 60 Gy, SRS boost, or brachy boost improve outcomes for GBM?
Despite most failures occurring locally, dose escalation attempts have been unsuccessful.
110
What is the Simpson resection grade for meningiomas? How does it relate to the risk of recurrence?
111
What are the outcomes of the RTOG 0424 study for high-risk LGG?
Phase II trial of high-risk LGG, which is defined as having ≥ 3 of the SATAN criteria
- 54 Gy w/ concurrent and adjuvant TMZ
- 3 yr OS: 73.1% (sig. improved compared to historical controls)
- 3 yr PFS: 59.2%
- Median OS: Not yet reached
112
What is the SOC for diffuse midline glioma (previously DIPG)?
- RT alone (clin and radiographic dx, bx gen not rec 2/2 morbidity, no benefit to CHT or surgery)
-- 54 Gy in 30 fx (sig tox if escalated to 60 Gy_
-- 39 Gy in 13 fx or 45 Gy in 15 fx may be non-inferior (Egyptian clin trial)
113
What mutation is associated w/ diffuse midline gliomas (previously DIPG)
H3 K27M
114
What is the QUANTEC 1 fx SRS dose constraint for the brainstem?
Dmax < 12.5 Gy → < 5% risk of neurotoxicity
115
Is observation appropriate for ependymomas?
- This is controversial
- Rarely: for G II ependymomas s/p GTR, observation may be appropriate
116
What are the outcomes of the Yamamoto (JLGK0901, Lanc Onc 2014) study investigating SRS for brain mets?
SRS w/o WBRT as a treatment for pts w/ 2-4 vs. 5-10 brain mets
- Median FU of 20.9 mos:
-- 1 brain met, median OS: 13.9 mos (p<0.0004)
-- 2-4 brain mets, median OS: 10.8 mos
-- 5-10 brain mets, median OS: 10.8 mos
- Need for salvage SRS: 42% vs. 43%
-- SE not sig. difference
-- Need for salvage after one brain. met: 33%
- Post-SRS survival among all patients
-- 6 mos: 73.8%
-- 12 mos: 50.0%
-- 24 mos: 27.5%
-- 36 mos-17.2%
117
What factors predicted improved OS per the multivariate analysis of Yamamoto Lanc Onc 2014 study investigating SRS for brain mets?
- Solitary lesion
- Female sex
- Age < 65 years
- KPS>80
- Stable extracranial disease
- No neurological symptoms
118
What is the conformity index and gradient index?
CI: Rx isodose volume / PTV (ideal: 1.2)
GI: vol of 50% of the Rx isodose / vol of Rx isodose (Ideal 3)
HI: max dose / Rx dose (Ideal: 2)
119
What are the contouring guidelines for post-op SRS?
- Fusing the preop T1-post contrast MRI w/ thin cuts
- Contouring the entire surgical tract
- Extending the CTV 5 to 10 mm along the dura underlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact
- Creating a margin of ≤5 mm into the adjacent sinus when preoperative venous sinus contact
was present
Soliman et al IJROBP 2017
120
Which cranial nerves exit out of which portions of the brainstem?
- Midbrain - III, IV
- **Mid-Pons - V**
- **Inferior Pons/Cerebellopontine angle - VI (anterior), VII (lateral), VIII (lateral)**
- Medulla - IX, X, XI, XII
Rule of 4s: 4 CN above pons, 4 within the pons, and 4 below the pons
121
What is the Rx dose for trigeminal neuralgia?
- 70-90 Gy to the nerve root
- Different inst. variations on which IDL should kiss the brainstem
122
What special PE should be performed during OTV for pts w/ GBM?
Calf tenderness for DVT
123
Which medication should be prophylactically initiated for patients undergoing SOC tx for GBM and why?
Pneumocystis Pneumonia (PCP) prophylaxis:
- TMP-SMX DS 3 times / week
124
What is the first-line therapy for trigeminal neuralgia?
medical (carbamazepine or other anticonvulsants)
125
What is the definition of a pituitary microadenoma?
micro: ≤ 10 mm
macro: 10-40 mm
Giant: > 40 mms
126
What are the components of the SINS classification system for spinal cord instability?
- 0-6: stable
- 7-12: Impending instability, NSGY consult recommended
- 13-18: unstable
127
What were the findings of the French trial for the treatment of GBM in the elderly (Keime-Gubert et al. NEJM 2007)?
- >70 YO and KPS ≥ 70 → RT (50.4 Gy) vs. best supportive care
- OS: 29.1 wks vs. 16.9 wks (SS)
- Trial stopped early due to a sig. Difference being detected
- RT doubles survival in this patient population
128
What scale can be used to grade facial nerve function?
House-Brackma**nn** scale → facial **n**erve
129
What scale can be used to assess Glomus Jugulare?
GJ: **G**lasscock **J**ackson
130
What scale can be used to assess hearing function after surgery for vestibular schwannoma?
Gardner-Robertson
131
Which scale can be used to grade the size and location of acoustic neuroma?
A**KOOS**tic neuroma → Koos grading scale
132
What is the estimated 5-year OS for skull-based chondrosarcomas vs. chordomas?
- Chondrosarcomas: 75-100%
- Chordomas: 50-75%
133
What are the expected outcomes following SRS for trigeminal neuralgia?
- Complete pain relief following SRS: 2/3
- Pain response maintenance at 1-3 yrs: 50%
134
What tumors are present in someone with NF2 syndrome?
NF2 aka MISME syndrome:
- Multiply Inherited Schwannomas (b/l)
- Meningiomas
- Ependymomas
135
What kind of cancers are a/w Gorlin syndrome?
non-melanoma skin cancers
136
What kinds of cancers are present in someone w/ VHL syndrome?
Clear cell renal carcinomas
Retinal hemangioblastomas
Pheochromocytomas
Pancreatic neuroendocrine tumors
137
Which seminal study supports the use of chemotherapy or radiation over the best supportive care for GBMs?
BTSG 6901
138
What are the contents of the cavernous sinus?
- Cranial Nerves: 3, 4, 5(1,2), & 6
-- Oculomotor nerve (CN III)
-- Trochlear nerve (CN IV)
-- Ophthalmic branch of the trigeminal nerve (CN V1)
-- Maxillary branch of the trigeminal nerve (CN V2)
-- Abducens nerve (CN VI).
- Blood Vessels: internal carotid artery
- Sympathetic plexus
139
Which mutations in gliomas are mutually exclusive?
- ATRX → often found in Astrocytomas
- TERT → often found in oligodendrogliomas and GBM IDHwt
140
What defines WHO I, II, III, IV gliomas according to the 2007 classification system?
- AMEN = Atypia, Mitosis, Endothelial proliferation, and Necrosis.
-- 1 criteria → WHO Grade II, Astrocytoma.
-- 2 criteria → WHO Grade III, Anaplastic Astrocytoma.
-- 3 criteria → WHO Grade IV, Glioblastoma.
Typically, among WHO Grade II astrocytomas, nuclear atypia is seen along with increased cellularity, but mitoses, endothelial proliferation, and necrosis are not.
141
What defines WHO I, II, III, IV gliomas according to the 2016 Louis update to the classification system?
It incorporates molecular markers:
- Grade 2
-- Diffuse astrocytoma (IDH-mutant)
-- oligodendroglioma (IDH-mutant and 1p/19q-codeleted)
- Grade 3
-- Anaplastic astrocytoma (IDH-mutant)
-- Anaplastic oligodendroglioma (IDH-mutant and 1p/19q-codeleted)
- Grade 4
-- Glioblastoma (IDH-wildtype or IDH-mutant)
-- Diffuse midline glioma (H3K27M-mutant).
142
What defines gliomas according to the 2021 Louis update to the classification system?
- Glioblastomas must be IDH-wildtype and are grade 4
- Astrocytoma, IDH-mutant are grade 2, 3, 4
- Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted are grade 2, 3
143
What biomarkers influence glioma grading in the current system?
- CDKN2A/B homozygous deletion results in a CNS WHO grade of 4, even without microvascular proliferation or necrosis
- TERT promoter mutation, EGFR gene amplification, or gain of 7 and loss of 10 (+7/-10) are sufficient to diagnose Glioblastoma, IDH-wild-type in the setting of an IDH-wildtype diffuse and astrocytic glioma in adults
144
What are the recommendations for CT sim/treatment planning/delivery for meningioma patients undergoing CF-RT per RTOG 0535?
* Tumor and OAR localization is based on preop and postop MRI.
* Non-invasive, stereotactic, relocatable immobilization is recommended for simulation and treatment delivery.
-- Immobilization devices may include a head cast, modified SRS frame, or camera-based localization system.
- The immobilization setup should be reproducible to within 5 mm.
- Orthogonal images obtained with film or EPID should be used to document isocenter setup accuracy for the 1st fraction.
-- Daily imaging techniques can be used, including BrainLab Exac Tract, which uses two orthogonal imaging panels irradiated with kV x-rays.
145
What are the recommended doses of RT for a primary **spinal** high G astrocytoma?
- 45-50.4 Gy
- Can be escalated to 60 Gy if below conus medullaris
146
What were the outcomes of the CCTG trial (Brown et al Lancet Onc '17) comparing SRS vs. SBRT?
SRS vs. WBRT (Brown et al, Lancet Onc '17):
- cognitive-deterioration-free survival: 3.7 vs. 3.0 mos (SS)
- Cognitive deterioration at 6 mos: 52% vs. 85% (SS)
- LC: 79.2% vs. 86.5% (NS)
- OS and leptomeningeal disease development were not SS
147
What are the key differences between adult vs. pediatric medulloblastoma?
- Adults, lateralized (50%) vs. pediatric, lateralized (10%)
- Desmoplastic tumors more common in adults
148
What are the findings of the RTOG 1205 trial of recurrent GBMs?
Recurrent GBM → Bevacizumab vs. Bev. + RT (35 Gy in 10 fx)
- 6 mo PFS: 29.1% vs. 54.3% (SS)
- Median OS: 9.7 mos vs. 10.1 mos (NS)
149
What were the results of the CeTeG-NOA-09 trial?
- Tested addition of lomustine to TMZ for **MGMT-methylated GBM treatment**
-- Unique CHT style: lomustine (100mg/m2) on D1, and TMZ 100-200 mg/m2 on D2-6 q6 weeks for up to 6C
- TMZ alone vs. TMZ+Lomustine (both arms 60 Gy in 30 fx RT)
-- Median OS: 31.4 mos → 48.1 mos
-- NO PFS benefit (16.7 mos for both)
-- ≥ Gr 3 tox: 51% vs. 59%
- Despite the OS benefit, lomustine is rarely used 2/2 study limitations:
-- Small n; discrepancy b/w PFS and OS (fishy, fishy); modified ITT analysis
150
How can you calculate the risk of myelitis after re-irradiation of the spinal cord?
Nieder et al, IJROBP 2006
151
What is the MOA of TMZ?
Alkylating agent
152
What is the Dmax constraint for Optic Chiasm and Optic Nerves for CFRT to keep the risk of RION low?
- Nerves: 55 Gy
- Chiasm: 56 Gy
-- Both keep the risk of neuropathy <3%
- 55-60 Gy → risk 3-7%
- > 60 Gy → risk > 7-20%
153
Is there any benefit to carmustine as a component of initial GBM treatment?
No
154
For skull-based chordoma s/p GTR f.b adjuvant RT to ≥ 70 Gy, what is the 5-year OS?
50-90%
155
What is the pathognomonic finding on a path for pilocytic astrocytomas?
Rosenthal fibers
156
What is the pathognomonic finding on a path for oligodendrogliomas?
Fried-egg appearance
157
What is the pathognomonic finding on a path for meningiomas?
Psommama bodies
158
What are the pathognomonic findings on a path for GBMs?
Prominent nuclear atypia
Necrosis
159
What is the tissue of origin of chordomas?
- Notochord remnant
- usually midline
160
What is the anatomic origin of chondrosarcomas?
- Petroclival bone
- Usually well-lateralized
161
What are the guidelines for vertebral body contouring when treating a patient w/ SBRT?
- Include adjacent elements
- See picture
162
What is the most common tox a/w TMZ?
- Hematologic tox
- Particularly, thrombocytopenias
163
What is the most common tox a/w 5-FU?
Mucositis
164
What is the most common tox a/w cisplatin?
Ototoxicity
165
What is the most common tox a/w taxanes?
Peripheral neuropathy
166
What is the overall response rate of brain mets from melanoma w/ different systemic agents sans RT vs. SRS?
- Pembro → 26% (Kluger JCO 19)
- IPI/NIVO → 56& (Tawbi NEJM 18)
- SRS → 90-95%
167
Which receptor on meningiomas makes it PET-avid (Dotatate)?
Somatostatin, picked up by dotatate
168
Which molecular/gene feature is a/w solitary fibrous tumors?
NAB2-STAT6
169
Which molecular/gene feature is a/w rhabdoid tumors of the kidney/CNS?
INI1
170
What is the usual imaging course for acoustic neuromas post-radiation?
- Slight growth
- Loss of enhancement
- Resolution to a scar
- Usually do not resolve fully
171
How are optic nerve sheath meningiomas generally managed?
- RT only; 50.4 Gy in 30 fx
- Surgery is very morbid
- LC: > 90%
- Vision preservation: 90%
- Vision improvement: 40%
172
How do you grade the severity of spinal cord compression?
The Bilsky System:
- 0: bone-only disease.
- 1a: epidural impingement w/o deformation of the thecal sac.
- 1b: deformation of the thecal sac w/o cord abutment.
- 1c: deformation of the thecal sac with cord abutment w/o compression.
- 2: cord compression with CSF visible around the cord.
- 3: cord compression w/o CSF visible around the cord.
173
What is the recommended imaging FU schedule for GBM pts post-RT?
- MRI 2-6 wks
- Then q2-4 mos for 2-3 yrs
174
In which decade of life are LGG and HGG present?
- 4th decade → LGG
- 6th decade → HGG
175
What is the lifetime risk of malignancies caused by RT treatment for benign intracranial conditions?
10-yr: 0.05%
176
What is the benefit of TMZ beyond 6 mos for GBM patients?
PFS but not OS, especially for MGMT-methylated patients
177
What are the results of the hippocampal avoidance trial (NRG CC001)?
- WBRT 30 Gy/10 fx vs. →🏆 hippocampal avoidance IMRT WBRT 30 Gy/10 fx; memantine for both
-- HA led to less executive function, learning, and memory deterioration. It also improved fatigue, difficulty speaking and remembering, interference in daily activities, and fewer cognitive symptoms
-- Alopecia grade 2 <10% (2D RT caused permanent alopecia!)
-- Hippocampus D100% < 9-10 Gy was the best dosimetric factor correlated with the outcome
178
How often should you get an MRI Brain after treatment for a meningioma?
- NCCN: 3,6,12 mo yr 1, q6-12 mos 2-5 yrs
- ROT: Meningioma Grade = # of times per year MRI
179
What is the SRS dose constraint for the cauda equina?
Dmax < 16 Gy (higher than spine)
180
What are the WHO classifications for different diffuse CNS tumors?
- IDH-mut + another deletion(s) (1p/19q or CDKN2A) makes tumors WHO G1
- 2 alterations required for oligo (IDH, 19/19q),
- 3 alterations required for astro (IDH, CDKN2A/B), ATRX could be retained or nto
- While IDH-wt is almost exclusively GBM, it requires further molecular/NGS confirmation for TERT-mutation, EGFR amplification, and/or +7/-10.
-- GBM can be dx even if no histologic features of WHO G4 tumors exist based on the former criteria.
181
In patients w/ metastatic melanoma to the brain, what is the objective response rate when treated w/ IPI/NIVO alone?
- Tawbi et al. 18, ORR = complete, partial, or stable response
- IPI/NIVO → 55-60% ORR
-- CR → 26%
-- PR → 30%
-- Stable for at least 6 mos → 2%
- Compare w/ single-agent therapy and SRS
-- Pembro → ORR 26% (Kluger et al, JCO '19)
-- Other systemic agents → ORR 25-30%
-- SRS → ORR > 90%
182
Which genetic mutations are a/w hereditary meningiomas?
- SMARCE1 Syndrome: Germline mutation in the SMARCE1 gene
-- Hereditary meningiomas, often involving multiple sites, even the spinal canal
-- Present in early childhood or adulthood
-- Mostly WHO G2, clear cell
183
Which area of the brain is a/w processing speed, which can atrophy w/ RT?
- Corpus callosum
- Hippocampus
184
At what vertebral levels do the spinal cord and cauda equina end in adults?
Spinal cord → L1-2
Cauda Equina → S1-2
185
Does the initial IDH mutation testing on a glioma test for all IDH mutations?
- No, it tests for the most common one (IDH1 R132H)
- Thus, if staining for IDH1 R132H is -ve → test for other IDH1/2 mutations
186
Are there any other agents, besides TTF, which can be added to the stereotypical STUPP regimen to improve survival in MGMT methylated GBMs?
- Yes, Lomustine!
- Improved median survival: 31.4 mos → 48.1 mos
- Many question the results, power of the trial, and how OS benefit could be demonstrated w/o a PFS benefit
187
What histopatholgic findings indicate a grade II meningioma until proven otherwise
- Chordoid and clear cell histopathologies
- Brain invasion
