CNS/Palliative Flashcards
What is the study question for Patchell II?
Whether postop RT after resection of single brain met improves neurologic control and increased survival
Number of patients on Patchell II
95
RCT arms for Patchell II
- WBRT (50.4 in 1.8 fractions)
2. Observation
OS results for Patchell II
WBRT: 48 weeks
Observation: 43 weeks
NSS
Tumor recurrence at site of original metastasis Patchell II
WBRT: 10%
Observation: 46%
In brain tumor recurrence Patchell II
WBRT: 18%
Observation: 70%
Death due to neurologic causes
WBRT: 14%
Observation: 44%
What percentage of observed patients eventually got RT on Patchell II
60%
Research question in Patchell I
Question of whether surgery benefits patients with single brain met
RCT arms for Patchell I
- Resection followed by WBRT (36/12)
2. Biopsy followed by WBRT (36/12)
How many patients were excluded from Patchell I due to histology not being malignant
11% (6 pts)
OS differences on Patchell I
Surg+WBRT: 40 weeks
WBRT: 15 weeks
Recurrence rate at original metastasis Patchell I
Surgery+WBRT: 20%
WBRT: 52%
After 3x10 or 4x5 for cord compression how many had stable or improved motor function at 1 month
88%
What percentage of patients could walk at 1 month after palliative RT
73%
TEACHH model, lowest survival score median survival
1.7 months
TEACHH model, highest survival score
19.9 months
Factors with negative prognosis for palliative RT
Lung/other vs. breast/prostate ECOG 2-4 Age >60 More prior courses palliative chemo Hospitalizations prior to palliative RT Hepatic mets
Most common site of bone mets
spine > pelvis > ribs > femur > skull
Most common distribution of spine mets
Thoracic (30-60%)
Lumbar (15-30%)
Cervical (<10%)
How were oligomets defined on SABR-COMET
1-5 mets
RCT arms for SABR-COMET
- SABR to all sites + standard of care systemic therapy
2. Systemic therapy alone
PFS differences in SABR-COMET
- SABR: 12 months
2. SOC: 6 months
OS differences in SABR-COMET
- SABR: 41 mos
- SOC: 28 mos
p=0.09
G2+ toxicities on SABR-COMET
- SABR: 29%
2. SOC: 9%
On the disease specific GPA, does higher or lower score correspond to better prognosis
higher (0-4)
On the DS-GPA which histology had best prognosis
breast
For brainstem mets SRS, limit healthy brainstem dose getting 10-12 Gy to X cc
1
What percentage of patients will develop brain mets
20-40%
Broca’s area location
inferior frontal gyrus of dominant hemisphere [usually left side in 75% of patients]
Broca’s aphasia aka
expressive aphasia – understand but cannot fluently speak
Wernicke’s area
transverse gyrus of the dominant temporal lobe
Wernicke’s aphasia aka
receptive aphasia - difficulty understanding language
Preferred steroid dose for new BM
8-32 mg dex loading
4q6h and taper as tolerated
RPA classes include which 3 factors
- Age <65
- KPS <70
- controlled primary
Class 1
KPS>70, age<65, controlled primary - MS of 7 months
Class 2
one risk factor
Class 3
all risk factors
Patchell 2 research question
Is adjuvant RT needed after resection?
QUARTZ trial design
NSCLC pts unsuitable for SRS or surgery randomized to
- WBRT
- best supportive care
QUARTZ results
No OS difference (9 weeks)
No QOL difference
NRG CC001 study (Brown)
RCT of
- WBRT + memantine
- HA-WBRT + memantine
Requirement for eligibility on CC001
no mets within 5 mm of hippocampus
What did HA-WBRT improve?
Less executive function deterioration at 4 months
Improved learning/memory at 6 months
Less fatigue at 6 months
Dose constraint for hippocampi
D100% < 9 Gy (bilateral)
RTOG 9508 study patients
1-3 mets
<4 cm
Not amenable to resection
RTOG 9508 study design
randomized to
- WBRT (37.5/15)
- SRS
RTOG 9508 fndings
OS advantage for SRS for 1 met (6.5 months vs. 4.9 months)
No OS for multiple
EORTC 22952 (Kocher) design
1-3 mets s/p surgery or SRS randomized to
- WBRT
- Observation
EORTC 22952 results
WBRT reduces intracranial recurrence and neurologic death
No diff in OS or functional independence
RTOG 90-05 design
SRS dose escalation study of previously irradiated primary brain tumors or brain mets
90-05 doses for <2cm
18-24 Gy
90-05 doses for 2-3 cm
15-18
90-05 doses for 3-4 cm
12-15
Rate of radionecrosis at 24 months from 90-05
11%
What is the expected intracranial response rate for ipi/nivo
26% CR
30% PR
Yamamoto 1-10 brain met study stratified patients into what groups
1 met
2-4 mets
5-10 mets
On Yamamoto study how were patients treated
SRS with GK
Median OS for 1 met
13.9 months
Median OS for 2-4/5-10 mets
both same 10.8 months
Brown study of memantine - dose of memantine
20 mg per day
How long did patients take memantine
6 months
What was primary endpoint in memantine study
decline in delayed recall at 6 months
What was the result?
less decline for memantine but not SS (p=0.059)
but also numerous other cognitive parameters improved with memantine
Why not SS?
probably too few analyzable patients
Peak incidence of HGG
65-75
What syndromes associated with HGG
NF1, NF2, Tuberous Sclerosis
What are the pathologic hallmarks of grade IV astrocytoma
Necrosis
Endothelial proliferation
What characteristic defines anaplastic gliomas
mitotic rate
What characteristic defines grade II gliomas
atypia
What mutations are much more frequently found in LGG
IDH mutations
IDH1 mutant appearance on MRI
On T2 confluent signal which is much lighter on FLAIR with brighter rim
What mutation associated with aggressive brainstem glioma
H3K27 mutant
What molecular markers in diffuse astrocytoma make them molecularly GBM
IDHwt
EGFR amplification
TERT mutation
+7/-10 chromosome
What is hallmark of oligodendroglioma
1p19q codeletion
ATRX loss is typically associated with
IDH mutant LGG
Most IDH mt tumors also show
CpG island methylated phenotype (CIMP) - low levels associated with poorer prognosis
CDKN2A deletion associated with better/worse prognosis
worse
For cancer, is N-acetylaspartate (NAA) be low or high
low
What marker should be high for spectroscopy in tumors
choline
Margin for HGG
GTV + 2 cm margin
Why is this margin used
90% of gliomas fail within 2 cm of original site
BTSG study concluded that >X Gy associated with OS benefit
50 Gy
MRC BR02 compared what dose levels
60 Gy vs. 45 Gy, 60 better
What is hyperfractionation
smaller dose per fraction, usually BID-TID
Accelerated fractionation
shorter duration of time, higher dose per treatment
Dose of temozolomide for concurrent
75 mg/m2 every day
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
Stupp trial arms
- RT alone (60/30)
2. RT with concurrent TMZ for 6 cycles
5 year OS advantage per Stupp
CRT: 10%
RT: 2%
Median OS per Stupp with CRT
14.6 months (v. 12 months)
AVAGLIO study showed that bev improves
QOL only
TTF study randomization
- Stupp + TTF
2. Stupp alone
How long per day is patient supposed to wear TTF
18 h
What did TTF improve?
OS improved from 16 to 21 months
TTF associated with what toxicity
mild to moderate skin toxicity in 52%
Roa study patient population
Age > 60
KPS > 50
Conclusion of Roa study
60/30 similar OS to 40/15 with less steroid requirement for 40/15 arm
Nordic trial arms
- 60 Gy
- 34/10
- TMZ alone
Patients on Nordic trial
Age >60
Finding of Nordic trial
60 Gy did worse than either other arm
If MGMT methylated, TMZ is better
Median survival of anaplastic gliomas
4 years
NOA-04 study (Wick 2016) design
- Chemo alone (either PCV or TMZ)
- RT alone
Once unacceptable toxicity or POD, the patients crossed over to the other arm
What patients included on NOA-04
anaplastic gliomas (unselected)
Results of NOA-04 trial
No difference in PFS or OS whether starting with chemo or RT
What is PCV chemo
procarbazine
CCNU (lomustine)
Vincristine
RTOG 9402 (Caincross) patient inclusion
anaplastic oligo or oligoastro
RTOG 9402 (Caincross) treatment arms
- PCV –> RT
2. RT alone (59.4)
What was the OS result for whole cohort?
No difference 4.6 years for both
Which group benefitted from PCV + RT
1p19q codel tumors
What is median OS for 1p19q deleted tumor with CRT
14.7 years
What is benefit of PCV+RT for IDH mutants
It improved OS irrespective of whether pt also had 1p19q codel
What is benefit of PCV+RT for IDH wt
No benefit from chemo
What is median OS for IDH mt tumor
9.4 years with CRT
What is median OS for IDH mt astro (non codel)
5.5 years with CRT
CATNON trial population
anaplastic gliomas, 1p19 non-codel
CATNON arms
- RT alone
- RT + TMZ adjuvant
- RT + concurrent/adjuvant TMZ
What is reported result of CATNON
adjuvant TMZ improves OS 44 to 56%
Concurrent TMZ may benefit which group
IDH mt
How many MRIs look worse 1 month after RT
50%
How many of those have pseudoprogression
2/3
What risk factor for pseudoprogression
MGMT methylated
What oncogene pathway associated with LGG
Ras
What is the path hallmark of pilocytic astrocytomas
Rosenthal fibers
What grade is pleomorphic xanthroastrocytoma
II
