Palliation of Brain and Spinal Cord Metastases

Question 1

Brain Metastases

What is the most common primary site?

Answer 1

Lung

Question 2

Brain Metastases

Most common presenting symptom?

Answer 2

Headache

Question 3

Brain Metastases

Most sensitive imaging modality?

Answer 3

contrast-enhanced MRI

Question 4

Brain Metastases

Appearance on MRI

Answer 4

iso to hypointense on T1,
hyperintense on T2,
enhance with contrast

Question 5

Brain Metastases

RPA I

Answer 5

KPS ≥70
age <65
no extracranial metastases
controlled primary

Question 6

Brain Metastases

RPA III

Answer 6

KPS <70

Question 7

Brain Metastases

What are the median survivals of RPA I, II, III respectively?

Answer 7

7. 1
8. 2
9. 3

(in months)

Question 8

Brain Metastases

Initial therapy which effectively improves edema and neurologic deficits?

Answer 8

corticosteroids

(Dexamethasone 4 or 8 or 16 mg per day with 4 week tapering schedule)

In the only randomized study,
all arms had similar KPS improvements at 7 days (54% to
70%) and 28 days (50% to 81%). The study concludes that 4 mg per day of
dexamethasone (with a taper over 4 weeks) is the preferable regimen. One
should be cautious, however, in interpreting the results of this study. Patients in
the 4 mg per day arm had to have the medication be reinstituted at a higher rate
than the patients in the 8 or 16 mg per day arms. Furthermore, the arm with the
greatest improvement in the KPS was the 16 mg per day arm when this was
tapered over 4 weeks, compared with any of the other arms. It can be argued that
higher KPS improvement arose from the maximal anti-inflammatory effects of
the initial higher doses, with the 4-week taper minimizing the late toxicity
associated with corticosteroids.

Question 9

Brain Metastases

What is the radiographic response rate in patients treated with WBRT? (Nieder et al)

Answer 9

59% (24% CR and 35% PR)

Question 10

Brain Metastases

Optimal supportive care is non-inferior to OSC+WBRT in patients with poor performance status KPS ≤70 and uncontrolled primary.

OSC+WBRT had a benefit in younger patients <60, good performance status KPS≥70 with controlled primary.

Which statement/s is/are TRUE?

Answer 10

Both.

QUARTZ trial (Quality of Life after Treatment of Brain Metastases)

Question 11

Brain Metastases

What domain of neurocognitive function is most susceptible to changes from WBRT use?

A. fine motor coordination
B. memory
C. executive function
D. spatial recognition

Answer 11

B. Memory

Question 12

Brain Metastases

Hippocampal avoidance WBRT resulted in a lesser mean decline (7%) in immediate recall compared to historical controls (30%)

TRUE or FALSE?
Identify the study cited.

Answer 12

False. It’s delayed recall.
***
RTOG 0933 phase II trial

WBRT(30/10) vs same regimen+HA

Question 13

Brain Metastases

The addition of memantine for 24 weeks to WBRT (37.5/15) resulted in a statistically significant effect on the preservation of delayed recall.

TRUE or FALSE?
Identify the pilot study cited.

Answer 13

False. Just a trend. It’s not significant.

RTOG 0614

Question 14

Brain Metastases

What study compared WBRT with or without HA in all patients who received memantine?

HA-WBRT-M was associated with lower NCF failure risk (adjusted hazard ratio (HR) = 0.74, p = 0.02) due to lower risk of deterioration in executive function at 4 mos (p = 0.01) and encoding (p = 0.049) and consolidation (p = 0.02) at 6 mos.

Answer 14

NRG-CC001

Question 15

Brain Metastases

According to Magnuson et al., what is the preferred sequence of TKI and SRS or WBRT in TKI-naive patients?

Answer 15

Upfront SRS/WBRT followed by TKI.
***
Both upfront SRS and WBRT use were
independently associated with improved OS relative to upfront EGFR-TKI. Use
of upfront SRS or WBRT was also associated with a trend toward lower risk of
intracranial progression, highlighting the potential for inferior outcomes with
deferral of early radiotherapy.

On the contrary, Gerber et al. found equivalent
survival outcomes with use of upfront EGFR-TKI or WBRT in patients with
EGFR mutant brain metastases

Question 16

Brain Metastases

Differentiate solitary from single lesion.

Answer 16

single lesion - the presence of only one intracranial lesion regardless of the extracranial disease
status

solitary lesion - the intracranial lesion being the only site of
metastatic disease

Question 17

Brain Metastases

According to the trials of Patchell, Noordijck, and Mintz,
surgery for single lesions have a benefit for single lesions but should be reserved for:

Answer 17

lesions causing life-threatening complications

lesions requiring pathologic confirmation

patients with good performance status with controlled extracranial disease burden

Question 18

Brain Metastases
SRS Boost Trials

What are the randomized trials comparing surgery and SRS?

What are the randomized trials assessing the role of surgery for multiple lesions?

(Based on Perez book)

Answer 18

NONE!

Question 19

Brain Metastases
SRS Boost Trials

This study “the first trial” was stopped early because of the large difference in the primary endpoint of 1-year LC in favor of SRS 92% vs. WBRT alone 0%.

Median OS, however were not significantly different, and recurrence reports were non standard.
No attempt were done to control for other factors.

Answer 19

Kondziolka et al.

University of Pittsburgh

Question 20

Brain Metastases
SRS Boost Trials

This study “the second trial” has only been published in abstract form, comparing SRS, WBRT, and WBRT+SRS.

survival times among the treatment arms
were similar.
SRS = experienced superior local
control,

51 of the patients had
surgical resection prior to entry into the study, and no attempt was made to stratify for previous surgery.

SRS arms cannot be considered
conventional because the peripheral dose was not individualized based on the
tumor size or volume.

Answer 20

Chougule et al.
Brown University

Although the authors conclude that the survival times among the treatment arms
were similar and that patients treated with SRS experienced superior local
control, no probability values are given. Furthermore, 51 of the patients had
surgical resection for at least one symptomatic brain metastasis prior to entry
into the study, and no attempt was made to stratify for previous surgery. The
inclusion of the surgically resected patients effectively made this a six-arm trial
and, therefore, the size of this trial was not large enough to support a meaningful
analysis. Finally, the radiation doses used in the SRS arms cannot be considered
conventional because the peripheral dose was not individualized based on the
tumor size or volume

Question 21

Brain Metastases
SRS Boost Trials

Inclusion criteria for RTOG 95-08 which compared WBRT vs. WBRT+SRS?

Answer 21

1 to 3 metastases

maximum diameter of 4 cm for the largest with the others not exceeding 3 cm.

WBRT 37.5 Gy/15

Question 22

Brain Metastases
SRS Boost Trials

Primary endpoint and results of RTOG 95-08?

Answer 22

OS - not statistically different between arms.

improved for patients with single metastasis on subgroup analysis

Question 23

Brain Metastases
SRS Boost Trials

SRS is associated with lower edema and corticosteroid use.

TRUE or FALSE?

Answer 23

TRUE
***
RTOG 95-08 did demonstrate that SRS boost is
associated with lower edema and corticosteroid use, countering a commonly
held notion that SRS actually increases the edema risk.

Question 24

Brain Metastases
SRS Boost Trials

What GPA scores benefited from SRS boost irrespective of the number of metastases? (based on RTOG 95-08)

Answer 24

3.5 to 4

Sperduto et al.

Question 25

Brain Metastases
Postop or PostSRS RT

What paremeter was not affected by witholding upfront WBRT and administering SRS (omission of WBRT)?

Answer 25

OS

Question 26

Brain Metastases
Postop or PostSRS RT

What paremeters worsen affected by witholding upfront WBRT and administering SRS (omission of WBRT)?

Answer 26

worse freedom from new brain metastasis

worse overall brain freedom from progression

(UCSF, Sneed et al.)

Question 27

Brain Metastases
Postop or PostSRS RT

In a study which evaluated upfront WBRT versus observation in resected metastatic lesions (Patchell et al), with primary endpoint of local and distant control,

surgical resection without WBRT led to higher “failure rate both at the original site and distant brain sites” compared to surgical resection +upfront WBRT.

TRUE or FALSE?

Answer 27

True.

This study met its primary end point and confirmed
the importance of postoperative WBRT in preventing brain failure and death
from neurologic causes

(not powered to detect for survival benefit)

Question 28

Brain Metastases
Postop or PostSRS RT

Postoperative SRS was documented to have higher 1 year LC rates, than observation.

OS did not differ.

TRUE or FALSE?

Answer 28

True.
Mahajan et al.

(this was just presented in an abstract/presentation form)

Question 29

Brain Metastases
Postop or PostSRS RT

In comparing postop WBRT vs postop SRS,

WBRT had a shorter cognitive deterioration free survival, but higher intracranial control rate than SRS, although surgical bed-RFS rates were similar.

TRUE or FALSE?

Answer 29

True.
Brown et al.
NCCTG N107/RTOG 1270

Question 30

Brain Metastases
Postop or PostSRS RT

What study evaluating the duration of functional independence in post surgical/post RT patients randomized to RT or observation showed a negative result with EBRT but subsequently associated with a decrease in decrease in 2-year local and distant relapse and overall decrease in the risk of neuronal death?

Answer 30

EORTC-22952-26001

Question 31

Brain Metastases

Based on Perez textbook described series,

what should be the minimum dose for reirradiation WBRT?

Answer 31

20 Gy (in 1.8 to 2 Gy/day)

Question 32

Brain Metastases

WBRT has been cited as a cause of neurocognitive decline.
According to the initial report by De Angelis, the estimated risk is 11% after 1 year.

Considering the beginning of RT, what is the ab initio adjusted risk?

Answer 32

approximately 2%

1.9% to 5.2% - De Angelis

Question 33

Spinal Cord Compression

Which is FALSE regarding the possible development of MSCC?

(a) continued growth and expansion of vertebral bone metastasis into the epidural space;
(b) neural foramina extension by a paraspinal mass;
(c) destruction of vertebral cortical bone, causing vertebral body collapse with displacement of bony fragments into the epidural space;
(d) rarely primary hematogenous seeding to the epidural space.

Answer 33

None of the choice.

All are true

Question 34

Spinal Cord Compression

What are the three most common tumors causing MSCC that accounts for 15% to 20% of cases?

Answer 34

breast, lung, and prostate

Question 35

Spinal Cord Compression

What is the most commonly involved level?

Answer 35

thoracic (60%-80%)

followed by lumbar (15% to 30%) then cervical (<10%)

Question 36

Spinal Cord Compression

What is the most common presenting symptom?

Answer 36

Back pain

Question 37

Spinal Cord Compression

What is the standard imaging modality which has a high specificity, sensitivity, and accuracy in diagnosing MSCC?

Answer 37

MRI of the “entire” spine with or without contrast

High-resolution CT scan or CT myelogram of the spine (for those with MRI contraindications)

Question 38

Spinal Cord Compression

Rapidity of onset, radiosensitivity of the tumor, and pretherapy ambulatory functions have been noted as important prognostic factors.

What is the single strongest predictor for ambulatory status after therapy?

Answer 38

time to development
of motor deficits before radiation from the start of any symptoms
(Rades et al.)

longer time - higher improvement rates
(i.e. >14 days compared to less than 7 days)

Question 39

Spinal Cord Compression

Rapidity of onset, radiosensitivity of the tumor, and pretherapy ambulatory functions have been noted as important prognostic factors.

After rapidity, what is the next best predictor for ambulatory status after therapy?

Answer 39

favorable histology

Question 40

Spinal Cord Compression

What is the initial regimen of steroids used in MSCC (as reported in the only randomized trial by Sorensen demonstrating increased ambulatory rates)?

Answer 40

96 mg IV bolus
96 mg oral per day x 3 days
10 day taper

Question 41

Spinal Cord Compression

What is the regimen of steroids considered sufficient in MSCC (as adjusted based on Heimdal toxicity report)?

Answer 41

10 mg IV loading dose followed by 4 to 6 mg every 6 to 8 hours before tapering.

Patients can be switched to oral after 24 to 48 hours.

Question 42

Spinal Cord Compression

Surgical technique of choice?

Answer 42

direct decompression, tumor debulking, spinal stabilization via instrumentation

Question 43

Spinal Cord Compression

Why is a posterior laminectomy usually not effective?

Answer 43

Most of the lesions in
MSCC involve the anterior portion of the vertebral body.

Therefore, a
laminectomy may not effectively relieve the compression simply by opening the
spinal canal and may actually worsen the stability of the spine.

Question 44

Spinal Cord Compression

Patchell reported the first phase III randomized trial testing the efficacy of direct decompressive surgery+RT versus RT alone.

This trial was terminated early when it met stopping rules when the primary end point of ambulation were met.

Which arm met the endpoint?

Answer 44

Surgery.

Question 45

Spinal Cord Compression

In-field recurrences are more common in protracted courses of RT fractionation.

TRUE or FALSE?

Answer 45

False.

(Rades et al.)

more common in 8x1 (24%)
than in 2x20(7%)

Question 46

Spinal Cord Compression

4 Gy x 5 fx is noninferior to 3 Gy x 10 in terms of response rates and effects on motor function in patients with poor to intermediate prognosis.

TRUE or FALSE?

Answer 46

True.

A more relevant randomized trial was reported by Rades et al. comparing a short course regimen (4 Gy × 5) to 30 Gy × 10 in patients with poor to intermediate survival prognosis, defined as having an estimated 6-month survival of 14% to 56% based on a validated scoring system.
Primary end point was motor function response rate showing improvement or no progression of motor deficits at 1 month.
Seventy-five percent of patients survived > 1 month.
One-month response rates were similar for both radiation regimens (87.2% to 89.6%, P = .73).
Both regimens also had similar RT effects on motor function at 3 and 6 months post treatment.
Ambulatory status at 1, 3, and 6 months was not significantly different between regimens.
Local progression-free survival and overall survival (median: 3.2 months) were also similar for both arms.
Based on this trial results, 4 Gy × 5 was deemed noninferior to 30 Gy × 10 and should be strongly considered for patients with poor prognosis in whom limiting treatment time and discomfort should be a high priority.

Question 47

Spinal Cord compression

What is the most common histology of pediatric MSCC?

Answer 47

neuroblastoma

Question 48

Spinal Cord compression

What is the mainstay of treatment in pediatric MSCC?

Answer 48

chemotherapy

Question 49

Spinal Cord compression

What is the most common primary tumor cause of a metastatic ISCM (intramedullary)?

Answer 49

lung
***
According to a review by Kalayci et al.,98
ISCM is most commonly secondary to a lung primary (54%), followed by breast
cancer (11%)

Question 50

Spinal Cord compression

What are the most common presenting symptoms of an ISCM (intramedullary)?

Answer 50

high sensory deficits, weakness, and sphincter dysfunction
***
high sensory deficits
(79%), sphincter dysfunction (60%), and weakness (91%)

Question 51

LCM

What are the most frequent cancers and histologies associated with LCM?

Answer 51

lung (particularly adenocarcinoma)

and

breast (particularly Her2 neu overexpressed ca, and ILCA)

Question 52

LCM

Which of the following is the most common presenting symptom?

spinal
cerebral
cranial nerve

Answer 52

spinal
***
The majority of patients present with signs and symptoms. According to the
review by Gleissner and Chamberlain, spinal symptoms (>60%) are the most
common, followed by cerebral (50%) and cranial nerve symptoms (40%).

Question 53

LCM

Commonly used treatment strategies for LCM?

Answer 53

IT-MTX + focal RT

Question 54

LCM

What chemotherapeutic agent was compared to MTX by Glantz et al. that led to a greater median time to neurologic progression 8 vs 4 weeks? (however no OS difference)

Answer 54

IT DepoCyt (cytarabine liposome injection)

Question 55

LCM

Patients treated by IT MTX, Ara-C and hydrocortisone had a significantly longer survival than those treated with MTX alone.

TRUE or FALSE?

Answer 55

True.
***
The only positive trial reported to date has been by Kim et al. from
Seoul National University. (18.2 weeks vs. 10.4 weeks; P
= .029).

Patients with adenocarcinoma of the lung in the multiagent arm had a
significant, longer survival (23.9 weeks vs. 10.4 weeks; P = .038)

Question 56

LCM

What is the penetration depth limit of IT chemotherapy (in mm) hence the use of focal treatments such as RT.

Answer 56

2 to 3 mm