CNS/Palliative Flashcards
1
Q
What is the study question for Patchell II?
A
Whether postop RT after resection of single brain met improves neurologic control and increased survival
2
Q
Number of patients on Patchell II
A
95
3
Q
RCT arms for Patchell II
A
- WBRT (50.4 in 1.8 fractions)
2. Observation
4
Q
OS results for Patchell II
A
WBRT: 48 weeks
Observation: 43 weeks
NSS
5
Q
Tumor recurrence at site of original metastasis Patchell II
A
WBRT: 10%
Observation: 46%
6
Q
In brain tumor recurrence Patchell II
A
WBRT: 18%
Observation: 70%
7
Q
Death due to neurologic causes
A
WBRT: 14%
Observation: 44%
8
Q
What percentage of observed patients eventually got RT on Patchell II
A
60%
9
Q
Research question in Patchell I
A
Question of whether surgery benefits patients with single brain met
10
Q
RCT arms for Patchell I
A
- Resection followed by WBRT (36/12)
2. Biopsy followed by WBRT (36/12)
11
Q
How many patients were excluded from Patchell I due to histology not being malignant
A
11% (6 pts)
12
Q
OS differences on Patchell I
A
Surg+WBRT: 40 weeks
WBRT: 15 weeks
13
Q
Recurrence rate at original metastasis Patchell I
A
Surgery+WBRT: 20%
WBRT: 52%
14
Q
After 3x10 or 4x5 for cord compression how many had stable or improved motor function at 1 month
A
88%
15
Q
What percentage of patients could walk at 1 month after palliative RT
A
73%
16
Q
TEACHH model, lowest survival score median survival
A
1.7 months
17
Q
TEACHH model, highest survival score
A
19.9 months
18
Q
Factors with negative prognosis for palliative RT
A
Lung/other vs. breast/prostate ECOG 2-4 Age >60 More prior courses palliative chemo Hospitalizations prior to palliative RT Hepatic mets
19
Q
Most common site of bone mets
A
spine > pelvis > ribs > femur > skull
20
Q
Most common distribution of spine mets
A
Thoracic (30-60%)
Lumbar (15-30%)
Cervical (<10%)
21
Q
How were oligomets defined on SABR-COMET
A
1-5 mets
22
Q
RCT arms for SABR-COMET
A
- SABR to all sites + standard of care systemic therapy
2. Systemic therapy alone
23
Q
PFS differences in SABR-COMET
A
- SABR: 12 months
2. SOC: 6 months
24
Q
OS differences in SABR-COMET
A
- SABR: 41 mos
- SOC: 28 mos
p=0.09
25
G2+ toxicities on SABR-COMET
1. SABR: 29%
| 2. SOC: 9%
26
On the disease specific GPA, does higher or lower score correspond to better prognosis
higher (0-4)
27
On the DS-GPA which histology had best prognosis
breast
28
For brainstem mets SRS, limit healthy brainstem dose getting 10-12 Gy to X cc
1
29
What percentage of patients will develop brain mets
20-40%
30
Broca's area location
inferior frontal gyrus of dominant hemisphere [usually left side in 75% of patients]
31
Broca's aphasia aka
expressive aphasia -- understand but cannot fluently speak
32
Wernicke's area
transverse gyrus of the dominant temporal lobe
33
Wernicke's aphasia aka
receptive aphasia - difficulty understanding language
34
Preferred steroid dose for new BM
8-32 mg dex loading
| 4q6h and taper as tolerated
35
RPA classes include which 3 factors
1. Age <65
2. KPS <70
3. controlled primary
36
Class 1
KPS>70, age<65, controlled primary - MS of 7 months
37
Class 2
one risk factor
38
Class 3
all risk factors
39
Patchell 2 research question
Is adjuvant RT needed after resection?
40
QUARTZ trial design
NSCLC pts unsuitable for SRS or surgery randomized to
1. WBRT
2. best supportive care
41
QUARTZ results
No OS difference (9 weeks)
| No QOL difference
42
NRG CC001 study (Brown)
RCT of
1. WBRT + memantine
2. HA-WBRT + memantine
43
Requirement for eligibility on CC001
no mets within 5 mm of hippocampus
44
What did HA-WBRT improve?
Less executive function deterioration at 4 months
Improved learning/memory at 6 months
Less fatigue at 6 months
45
Dose constraint for hippocampi
D100% < 9 Gy (bilateral)
46
RTOG 9508 study patients
1-3 mets
<4 cm
Not amenable to resection
47
RTOG 9508 study design
randomized to
1. WBRT (37.5/15)
2. SRS
48
RTOG 9508 fndings
OS advantage for SRS for 1 met (6.5 months vs. 4.9 months)
| No OS for multiple
49
EORTC 22952 (Kocher) design
1-3 mets s/p surgery or SRS randomized to
1. WBRT
2. Observation
50
EORTC 22952 results
WBRT reduces intracranial recurrence and neurologic death
| No diff in OS or functional independence
51
RTOG 90-05 design
SRS dose escalation study of previously irradiated primary brain tumors or brain mets
52
90-05 doses for <2cm
18-24 Gy
53
90-05 doses for 2-3 cm
15-18
54
90-05 doses for 3-4 cm
12-15
55
Rate of radionecrosis at 24 months from 90-05
11%
56
What is the expected intracranial response rate for ipi/nivo
26% CR
| 30% PR
57
Yamamoto 1-10 brain met study stratified patients into what groups
1 met
2-4 mets
5-10 mets
58
On Yamamoto study how were patients treated
SRS with GK
59
Median OS for 1 met
13.9 months
60
Median OS for 2-4/5-10 mets
both same 10.8 months
61
Brown study of memantine - dose of memantine
20 mg per day
62
How long did patients take memantine
6 months
63
What was primary endpoint in memantine study
decline in delayed recall at 6 months
64
What was the result?
less decline for memantine but not SS (p=0.059)
| but also numerous other cognitive parameters improved with memantine
65
Why not SS?
probably too few analyzable patients
66
Peak incidence of HGG
65-75
67
What syndromes associated with HGG
NF1, NF2, Tuberous Sclerosis
68
What are the pathologic hallmarks of grade IV astrocytoma
Necrosis
| Endothelial proliferation
69
What characteristic defines anaplastic gliomas
mitotic rate
70
What characteristic defines grade II gliomas
atypia
71
What mutations are much more frequently found in LGG
IDH mutations
72
IDH1 mutant appearance on MRI
On T2 confluent signal which is much lighter on FLAIR with brighter rim
73
What mutation associated with aggressive brainstem glioma
H3K27 mutant
74
What molecular markers in diffuse astrocytoma make them molecularly GBM
IDHwt
EGFR amplification
TERT mutation
+7/-10 chromosome
75
What is hallmark of oligodendroglioma
1p19q codeletion
76
ATRX loss is typically associated with
IDH mutant LGG
77
Most IDH mt tumors also show
CpG island methylated phenotype (CIMP) - low levels associated with poorer prognosis
78
CDKN2A deletion associated with better/worse prognosis
worse
79
For cancer, is N-acetylaspartate (NAA) be low or high
low
80
What marker should be high for spectroscopy in tumors
choline
81
Margin for HGG
GTV + 2 cm margin
82
Why is this margin used
90% of gliomas fail within 2 cm of original site
83
BTSG study concluded that >X Gy associated with OS benefit
50 Gy
84
MRC BR02 compared what dose levels
60 Gy vs. 45 Gy, 60 better
85
What is hyperfractionation
smaller dose per fraction, usually BID-TID
86
Accelerated fractionation
shorter duration of time, higher dose per treatment
87
Dose of temozolomide for concurrent
75 mg/m2 every day
88
Dose of temozolomide for adjuvant
150 mg/m2 day 1-5 of 28 day cycle 1
| 200 mg/m2 day 1-5 of 28 day cycle 2-6
89
Stupp trial arms
1. RT alone (60/30)
| 2. RT with concurrent TMZ for 6 cycles
90
5 year OS advantage per Stupp
CRT: 10%
RT: 2%
91
Median OS per Stupp with CRT
14.6 months (v. 12 months)
92
AVAGLIO study showed that bev improves
QOL only
93
TTF study randomization
1. Stupp + TTF
| 2. Stupp alone
94
How long per day is patient supposed to wear TTF
18 h
95
What did TTF improve?
OS improved from 16 to 21 months
96
TTF associated with what toxicity
mild to moderate skin toxicity in 52%
97
Roa study patient population
Age > 60
| KPS > 50
98
Conclusion of Roa study
60/30 similar OS to 40/15 with less steroid requirement for 40/15 arm
99
Nordic trial arms
1. 60 Gy
2. 34/10
3. TMZ alone
100
Patients on Nordic trial
Age >60
101
Finding of Nordic trial
60 Gy did worse than either other arm
| If MGMT methylated, TMZ is better
102
Median survival of anaplastic gliomas
4 years
103
NOA-04 study (Wick 2016) design
1. Chemo alone (either PCV or TMZ)
2. RT alone
Once unacceptable toxicity or POD, the patients crossed over to the other arm
104
What patients included on NOA-04
anaplastic gliomas (unselected)
105
Results of NOA-04 trial
No difference in PFS or OS whether starting with chemo or RT
106
What is PCV chemo
procarbazine
CCNU (lomustine)
Vincristine
107
RTOG 9402 (Caincross) patient inclusion
anaplastic oligo or oligoastro
108
RTOG 9402 (Caincross) treatment arms
1. PCV --> RT
| 2. RT alone (59.4)
109
What was the OS result for whole cohort?
No difference 4.6 years for both
110
Which group benefitted from PCV + RT
1p19q codel tumors
111
What is median OS for 1p19q deleted tumor with CRT
14.7 years
112
What is benefit of PCV+RT for IDH mutants
It improved OS irrespective of whether pt also had 1p19q codel
113
What is benefit of PCV+RT for IDH wt
No benefit from chemo
114
What is median OS for IDH mt tumor
9.4 years with CRT
115
What is median OS for IDH mt astro (non codel)
5.5 years with CRT
116
CATNON trial population
anaplastic gliomas, 1p19 non-codel
117
CATNON arms
1. RT alone
2. RT + TMZ adjuvant
3. RT + concurrent/adjuvant TMZ
118
What is reported result of CATNON
adjuvant TMZ improves OS 44 to 56%
119
Concurrent TMZ may benefit which group
IDH mt
120
How many MRIs look worse 1 month after RT
50%
121
How many of those have pseudoprogression
2/3
122
What risk factor for pseudoprogression
MGMT methylated
123
What oncogene pathway associated with LGG
Ras
124
What is the path hallmark of pilocytic astrocytomas
Rosenthal fibers
125
What grade is pleomorphic xanthroastrocytoma
II
126
What mutation is associated with pleomorphic xanthroastrocytoma
BRAF
127
How is gemistocytic astrocytoma classified
technically grade 2 but more aggressive
128
What does 1p19q predict
chemosensitivity
129
What path marker for grade II astrocytoma
ATRX loss
130
Median age of presentation of LGG
35
131
Most powerful predictor of OS in LGG
age (younger better)
132
Negative risk factors for LGG
```
Age >40
Astrocytoma histology
Tumor size 6 cm
Tumor crossing midline
Neuro deficit pre surgery
```
133
How many LGG risk factors is low risk
2 (median survival of 7.7 years)
134
What is the 5 year OS for observed LGG after resection
93%
135
EORTC 22845 (non believers study) design
supratentorial LGG randomized to
1. observation
2. RT (54 Gy)
136
Results of 22845
RT improved PFS, no diff OS
137
What was rate of transformation to HGG
70%
138
What proportion of delayed RT group needed RT
65%
139
What is criticism of this study?
25% path review were high grade
140
RTOG 9802 design
Resected LGG randomized to
1. RT --> 6 cycles PCV
2. RT alone
141
High risk patients on 9802
Age < 40 with STR
| Age > 40 with any resection
142
How were Low risk patients treated
observation
143
What was OS for low risk
median survival 13 years
144
What was the benefit of PCV for high risk patients
Improved OS (13.3 vs. 7.8 years)
145
What factors were associated with improved PFS/OS
Receipt of PCV
| Oligodendroglioma
146
Which patients did not benefit from PCV
IDHwt
147
Question in EORTC 22944
Compared two dose levels for LGG
| 45 vs. 59.4
148
What is gender preponderance of meningioma
2-3x more common in women
149
What genetic syndrome has higher rates of meningioma
NF2
150
Risk of recurrence for low risk meningioma
5%
151
Atypical meningioma risk of recurrence
40%
152
Anaplastic/malignant meningioma risk of recurrence
80%
153
Skull base meningiomas are likely to be higher/lower grade than convexity meningioma
lower
154
Grade II meningioma has how many mitoses per HPF
>4
155
Grade III meningioma has how many mitoses per HPF
>20
156
Simpson I or V is most complete
I
157
Dose for grade I meningioma
45-57.6
158
SRS dose for meningioma
12-16 Gy x1
159
What is max size for meningioma
3-4 cm in max diameter
160
Site associated with significant edema after SRS
parasagittal/convexity
161
Dose for grade II meningioma if GTR
54/30
162
Dose for grade II meningioma if STR
60/30
163
Treatment volumes for conventional fractionation
GTV + 2cm
164
Should dural tail be included in CTV?
no
165
RTOG 0539 treatment of low risk
observation
166
what is low risk
GTR or STR of who grade I
167
what is intermediate risk
recurrent grade I
| GTR grade II
168
treatment for intermediate risk meningioma
54/30
| CTV = GTV + 1 cm
169
what is high risk
STR grade II
recurrent grade II
any grade III
170
treatment for high risk
60/30
CTV= GTV+2 cm
6 Gy boost to GTV + 1 cm
171
Bilateral acoustic neuromas are pathognomonic for
NF2
172
NF1 is associated with which tumor
optic pathway gliomas
173
Acoustics preferentially impact what type of hearing?
high frequency
174
What score is used for facial nerve function
House-Brackmannn score
175
Where do schwannomas arise
vestibular portion of CN VIII
176
SRS dose for acoustic neuroma
12-13 Gy
177
Dose in fractionated RT
45/25
178
Local control of acoustics
90%
179
MEN-1 syndrome associated with
pituitary
pancreatic
parathyroid tumors
180
What nerves are in cavernous sinus
```
CN III
CN IV
CN V1
CN V2
CN VI
```
181
Posterior lobe of pituitary controls which hormones
oxytocin and ADH
182
Macroadenomas are larger than
1 cm
183
Atypical adenoma has MIB-1 score of
>3%
184
Are most adenomas functional or nonfunctional
nonfunctional
185
Most common functional pituitary tumor
prolactinoma
186
Prolactin levels associated with microadenoma
30-100
187
Prolactin levels associated with macroadenoma
>100
188
What is 1L for proalactioma
bromocriptine or cabergoline
189
If GH is elevated, what other hormone is elevated
IGF-1
190
SRS dose for non-functional adenoma
14-18 Gy
191
SRS dose for functional adenoma
18-35 Gy
192
Conventional dose for non-functional adenoma
45/25
193
Conventional dose for functional adenoma
50-54 Gy
194
Which of the functional variants is more aggressive
TSH secreting
195
Most common type of spinal lesion
extradural
| extramedullary
196
Most common intradural extramedullary tumors
meningioma
| schwannoma
197
Most common location of ependymoma failure
locally
198
What structure is chordoma derived from
notochord
199
From Patchell postop spine study, what % who were non ambulatory became ambulatory
60%
200
Dose for AVM
SRS to 18-25 Gy
201
Dose for trigeminal neuralgia
85 Gy to 100% IDL
202
Median time to pain relief after trigeminal neuralgia treatment
1 month
203
What proportion are pain free
50-60%
204
PCNSL how any present with single lesion?
66%
205
Where is most common location for PSCNL
frontal lobe
206
What is one of the radiographic hallmarks of PCNSL
multiple periventricular enhancing lesions
207
What is OS for PCNSL with RT alone
1 year
208
General treatment for PCNSL
1. High dose MTX
| 2. Consolidation with WBRT or Ara-C or HD MTX --> ASCT
209
Dose of WBRT
23.4/13
210
Dose of HD MTX
3.5 g/m2
211
Chemo of choice
R-MVP
MTX
Vincristine
Procarbazine
212
CN II palsy
pupil will react but not accomodate
213
CN III palsy
oculomotor palsy - eye will be down and out
214
CN IV palsy
controls superior oblique
| eye deviates up and inward towards nose
215
CN VI palsy
abducens nerve, controls lateral rectus
| unable to ABDUCT eye
216
Small choroidal melanoma size
1.5 - 2.4 mm height
| 5-16 mm diameter
217
Medium choroidal melanoma size
2.5-10 mm height
| <16 mm diameter
218
Large choroidal melanoma size
>10 mm height
| >16 mm diameter
219
Isotope used for plaque brachy
I-125 with gold shield
220
What is the size of tumor which can be treated with plaque
up to 18 mm in diameter
| 8-10 mm thick
221
COMS study patients
medium sized melanomas
222
COMS study arms
RCT of
1. enucleation
2. plaque brachy
223
What was COMS finding
OS same in both arms 81%
224
How many patients needed enucleation after plaque
10%
225
What was the brachy dose utilized
85 Gy to apex
226
Dose of RT used for charged particles for uveal melanoma
50-70Gy
227
Myxopapillary ependymomas are typically located where
spine
228
What genetic alteration associated with ependymoma
RELA fusion
229
CSF relapse after local treatment of ependymoma
5-15%
230
What is RT strategy for ependymoma
IF to 54-59.4
| CSI ONLY if dissemninated disease
231
When does SMART syndrome occur
10-20 years after RT
| Stroke like migraines
232
How to treat SMART syndrome
anti-epileptics
233
Optic nerve meningioma typical RTR dose
50.4 in 1.8 Gy fractions
234
What is rate of vision preservation for RT alone for optic sheath meningiomas
90%
235
Is biopsy needed for optic sheath meningioma
no
236
Where does spinal cord end level
L1-L2
237
Where does thecal sac end
S2
238
Estimated 5y OS for newly diagnosed WHO grade II glioma
60-70%
239
What share of patients treated for trigeminal neuralgia will have complete response to SRS
75%
240
For how many of these patients will the response be durable?
50%
241
RTOG 0424 design
single arm phase II of LGG patients with >3 risk factors receiving RT with concurrent/adjuvant TMZ
242
What dose of RT used on 0424
54/30
243
What were the LGG risk factors
```
Age >40
Tumor >6cm
Tumor crossing midline
STR
Astrocytoma histology
preop neuro deficit
```
244
Three year OS for LGG
74%
245
Five year OS for LGG
61%
246
What did this study conclude about methylation status
Demonstrated increased efficacy of TMZ in methylated patients
247
RTOG optic chiasm dose constraint
56 Gy to point dose
248
RTOG optic nerve dose constraint
55 Gy point
249
RTOG retina dose constraint
50 Gy point
250
What percentage of patients will develop a pituitary deficiency after pit RT
100%
251
Most common hormone lost from pit RT
GH
252
Next most common
gonadotropins
253
least most common hormone lost
TSH
254
2 year OS for RT alone (Stupp)
11%
255
2 year OS for RT+TMZ (Stupp)
27%
256
5 year OS for RT alone (Stupp)
2%
257
5 year OS for RT+TMZ (Stupp)
10%
258
Rate of long term control for nonfunctional pituitary adenoma with RT or Surgery
90%
259
RTOG 05-39 margins for malignant meningioma
60 Gy with 1 cm margin
| 54 Gy with 2 cm margin
260
Obliteration rate of AVMs with radiosurgery
85%
261
Risk factors for myelopathy with spinal retreatment
Cumulative BED > 120
<6 months between courses
Any course with BED>102
262
Factors predicting more indolent meningioma
1. Hypointense on T1 imaging
2. Calcifications
3. Older pt age
4. No growth on serial scans
263
For secretory pit adenomas what should happen to anti-secretory meds
held for several weeks before RT
264
RTOG/NRG recommendation for gbm contours
Two dose levels 46 and 60 Gy
265
ESTRO contouring guidelines
single dose level of 60 Gy
| cavity + T1 post contrast expanded by 2 cm and then +/- FLAIR
266
What nerves pass through cavernous sinus
```
III
IV
V1
V2
VI
```
267
Where does CN II exit
optic canal
268
Where do CN VII and VIII pass
internal auditory canal
269
NCCTG trial (Brown et al) compared what for resected brain met
1. SRS
| 2. WBRT
270
What did it conclude
WBRT had improved local control and distant brain control
| SRS had improved cognitive function
271
Perry short course w/wo TMZ median OS
TMZ+40: 9.3 months
| 40 Gy: 7.6 months
272
Roa II study design
1. 40/15
| 2. 25/5
273
Patients included on Roa II
frail: age >50, KPS 50-70
elderly/frail: age >65, KPS 50-70
elderly: age>65, KPS 80-100
274
OS for two Roa II arms
NSS different
7. 9 mos
6. 4 mos
275
RTOG CTV expansions
CTV1 (46 Gy) - FLAIR + 2 cm
| CTV2 (60 Gy) - T1post con + 2 cm
276
RTOG recommends trimming CTV to what around natural barriers
0.5 cm
277
Rate of compression fractures following spine sbrt from saghal paper
14%
278
Saghal identified what as risk factors
Higher dose (>20 Gy/fx)
baseline fracture
lytic tumor
spinal deformity
279
If fractures occur, what period
within 4-6 months post SBRT
280
Recommended dose range for AVM with radiosurgery
20-24 Gy
281
t(1;13) is associated with which malignancy
alveolar rhabdo
282
For postop SRS, guidelines recommend covering how long along dura of bone flap
5-10 mm
283
Rate of pseuoprogression after TMZ-RT
20-30%
284
In the postop SRS study, what is 12 month freedom from local failure for postop SRS
72%
285
In the postop SRS study, what is 12 month freedom from local failure for observation
43%
286
Which CN come off medulla
CN IX-XII
287
Which CN come off midbrain
CN III, IV
288
Which CN comes off mid pons
V
289
Risk of tumor progression at 5 years for completely resected LGG without adjuvant RT
50%
290
Which factors predicted worse PFS
Preop tumor > 4cm
Astrocytoma histology
Residual tumor > 1cm
291
RTOG constraint for brainstem
60 Gy
292
Rate of facial numbness after trigeminal neuralgia SRS
3-15%
293
SCORE-2 for cord compression finding
4x5 is not significantly inferior to 3x110 for patients with poor to intermediate expected survival
294
SCORAD trial question
8x1 vs. 4x5 for cord compression for nonoperative patients
295
Primary outcome of SCORAD trial
ambulatory status at 8 weeks post RT
296
Result of SCORAD
8x1 technically didn't meet noninferiority margin but similar, no differences in other outcomes
297
RPA class 3 has OS of how many months
2 months
298
RPA class 2 has OS of how many months
4 months
299
RPA class 1 has OS of how many months
7 months
300
From RTOG 9508 (WBRT + SRS boost) which groups benefitted from SRS boost
1. Single brain met (improved OS)
2. RPA class 1
3. Squamous or non-small cell histology
301
RTOG 9714 (Hartsell) patient inclusion
Breast or prostate patients
| 1-3 sites of painful bone mets with mod-severe pain
302
RTOG 9714 (Hartsell) arms
1. 8 Gy x 1
| 2. 300 x 10
303
Overall response rate for pain control in 9714
66%
304
At 3 months how many no longer required narcotics
33%
305
Retreatment rate for 8 Gy x 30 Gy
18% vs. 9%
306
Toxicity rates for 8 Gy x 30 Gy
10% vs. 17%
307
What is a solitary brain met
Single brain met with no extracranial metastatic disease
308
Rate of pain flare in patients getting palliative RT for bone mets
30-40%
309
Dose of dex used in randomized study to minimize pain flares
8 mg prior to start of RT and 4days post treatment
310
By how much did prophylactic dex reduce pain flare
10%
311
Aoyama study how many mets
1-4
312
What was brain recurrence rate at 12 months for SRS alone
76%
313
What was brain recurrence rate at 12 months for SRS+WBRT
47%
314
Aoyama other outcomes
No differences in death from neurologic causes or OS
