1
Q
What were the pt population, randomization, and endpoint of the Patchell 2005 study for metastatic epidural spinal cord compression?
A
- Pts: spinal cord compression caused by metastatic cancer
– ≥ 1 Neurologic sx, including pain
– Paraplegia ≤ 48 hrs
– Radiosensitive tumors (lymphomas, leukemias, MM, GCT) excluded
– Most pts had anteriorly located tumors tx w/ anterior or lateral approach corpectomy if randomized to the surgical arm. - Randomization:
– Surgical decompression f/b RT (30/10)
– RT alone (30/10)
— many unstable pts ended up in this arm, as this study was conducted before the SINS score was in use - Primary Endpoint: ability to walk
– “A patient was deemed ambulatory if he or she could take at least two steps with each foot unassisted (4 steps total), even if a cane or walker was needed”
2
Q
What were the pt results and the conclusion of the Patchell 2005 study for metastatic epidural spinal cord compression?
A
- Results: Surgery f/b RT vs. RT alone
– Post-treatment ambulatory rate: 84% vs. 57% (p=0.001)
– Retained ability to walk: 122 days vs. 13 days (p=0.003)
– Regained the ability to walk: 62% vs. 19% (p=0.012)
– Dexamethasone required: 1.5 mg vs. 4.5 mg (p=0.0093)
– Daily morphine equivalent: 0.7 mg vs. 4.8 mg (p=0.002) - Conclusion: Direct decompressive surgery f/b PORT is superior to RT alone for patients with spinal cord compression caused by metastatic cancer with respect to ability to ambulate and requirements for steroids and narcotics
3
Q
How was walking defined in the Patchell 2005 study for metastatic epidural spinal cord compression?
A
“A patient was deemed ambulatory if he or she could take at least two steps with each foot unassisted (4 steps total), even if a cane or walker was needed”
4
Q
What were the pt population, randomization, and endpoint of the first Patchell 1990 study for brain metastases?
A
- Pt: 48 patients with a single brain metastasis
– 11% were excluded as their surgical path did not show cancer - Randomization:
- S-WBRT: Surgical removal of metastatic lesion f/b WBRT (36 Gy in 12 fx w/ Co-60)
- Bx f/b WBRT (36 Gy in 12 fx w/ Co-60)
- Primary EP: OS
1st Patchell: Everyone gets RT
2nd Patchall: Everyone gets Surgery
5
Q
What were the results of the first Patchell 1990 study for brain metastases?
A
- S-WBRT vs. bx-WBRT only
- OS: 40 weeks vs. 15 weeks (p<0.001)
- Recurrence rate at the original site: 20% vs. 52% (p<0.02)
- Time to recurrence at original site: >59 weeks vs. 21 weeks (p<0.0001)
- Median time to death from neurological causes: 62 weeks vs. 26 weeks (p<0.0009)
- Median length of functional independence: 38 weeks vs. 8 weeks (p<0.005)
- Conclusion: Surgery f/b WBRT improves OS, local control, and QoL compared to WBRT alone in patients with one brain metastasis
6
Q
What were the pt population, randomization, and endpoint of the second Patchell 1998 study for brain metastases?
A
- Goal: to determine if surgical resection f/b PORT for patients with a single metastasis improved neurological control and increased survival.
- Randomization following surgery:
– WBRT (50.4 Gy in 28 fx)
– Observation - Primary EP: Recurrence within the brain
- Secondary EP: OS, cause of death, preservation of the ability to function independently.
1st Patchell: Everyone gets RT
2nd Patchall: Everyone gets Surgery
7
Q
What were the results and conclusions of the second Patchell 1998 study for brain metastases?
A
- WBRT vs. Obs:
– In-brain tumor recurrence: 18% vs. 70% (p<0.001)
– Recurrence at the original site: 10% vs. 46% (p<0.001)
– Recurrence not at original site: 14% vs. 37% (p<0.01)
– Time to recurrence: 50 wks vs. 27 wks (p<0.001)
– Death 2/2 neurological causes: 14% vs. 44% (p=0.003)
– OS: 48 wks vs. 43 wks (p=0.39)
– 60% of obs pts eventually received RT - Conclusion: Patients with 1 brain metastasis who receive surgery f/b PORT experience fewer in-brain tumor recurrences and are less likely to die of neurological causes versus those treated with surgery alone.
8
Q
Do pts receiving 5 fx RT for spinal cord compression do better if they receive it over five days (M-F) than if they do it over 7 days (RT interrupted by a 2 day weekend?
A
No
9
Q
Which ABX can be used for PJP prophylaxis in high-risk pts?
A
- TMP-SMX DS thrice weekly
10
Q
What was the pt population, randomization, and endpoint of the Phase II SABR-COMET trial (Lancet, 2019)?
A
- Phase II study of pts w/ oligomet recurrence (1-5 metastases) and controlled primary.
– All histologies enrolled, but the most common were colorectal breast, lung, prostate
– Most common metastatic sites were adrenal, bone, lung, liver - Randomization: SoC palliative therapy ± SABR to all sites
– Most common RT regimens were 35/5, 60/8, and 54/3
11
Q
What were the results of the Phase II SABR-COMET trial (Lancet, 2019)?
A
- SoC vs. SoC w/ SABR to all sites:
– Median PFS: 6 vs. 12 mos (SS)
– 8-yr PFS: 0 vs. 21.3% (SS)
– Median OS: 28 vs. 48 mos (SS)
– 8-yr OS: 13.6 vs 27.2% (SS)
– ≥ Gr 2 tox: 9.1 vs. 30.3% (SS)
– NS grade 3-5 toxicities or differences in QOL - Conclusion: The addition of ablative radiotherapy may provide PFS and OS benefits for patients w/ 1-5 metastases
12
Q
What is the first step in managing a pt w/ metastatic cord compression a/w neurologic deficits?
A
Initiate steroids!
13
Q
What is the general steroid admin protocol for pts w/ metastatic cord compression a/w neurologic deficits?
A
- 8-10 mg IV dexamethasone bolus (or equivalent) f/
-16 mg/day (usually in twice-daily to four-time daily)
– 4 mg q6h - Patients with dense paraparesis (Grade 3 or worse) should be considered for higher bolus (100 mg) and maintenance doses (up to 96 mg/day), but the risk of serious adverse events should be considered.
- *Patients with radiographic spinal cord compression but no neurologic deficits do not require steroids
14
Q
Should you initiate steroids in pts w/ spinal cord compression w/o neurologic deficits?
A
Not always
15
Q
What is the general recommendation regarding the use of steroids in the management of metastatic extramedullary spinal cord compression (MESCC)?
A
- Initiate steroids for any patient w/ neurologic deficits suspected or confirmed to have MESCC, particularly if they are being treated w/ ≤ 5 fx RT
- Patients being treated with surgery will need PORT and should receive maintenance steroids.
- Those treated w/ ≥ 6 fx RT w/ no neurologic deficits or those prescribed high-dose steroids can have the steroids weaned over ≥ 2 weeks once treatment is started
16
Q
What were the findings of the Rades et al. IJROBP 2011 paper examining short (8/1 and 20/5) vs long course (30/10 or 50/20) radiation therapy for the treatment of spinal cord compression?
A
- Short (8/1 and 20/5) vs long course (30/10 or 50/20) RT:
– 1-year LC: 61% vs. 81% (p=0.005)
– 1-year OS: 23% vs. 30% (p= 0.28)
– Motor function improvement: 37% vs. 39% (p=0.95)
17
Q
What did the SCORAD III trial examining short vs. long course RT for malignant spinal cord compression show?
A
1 fx was not non-inferior to multi-fx RT in the treatment of malignant spinal cord compression w/ regard to ambulatory status at 8 weeks
18
Q
How was RT prescribed in the Mahajan et al 2017 trial looking at post-op SRS vs. observation in pts w/ resected brain mets?
A
- Dose depends on cavity size:
- ≤ 10 cc → 16 Gy
- 10.1-15 cc → 14 Gy
- > 15 cc → 12 Gy
- Used 1 mm margins around the resection cavity
19
Q
What is the LC benefit of using a 0 mm vs. 2 mm margin for brain met SRS?
A
- 2 mm vs. 0 mm
– 1 yr LF rate: 3% vs. 8%, p=0.042 (Choi et al IJORBP 2012)
20
Q
What were the results of the Mahajan et al 2017 trial looking at post-op SRS vs. observation in pts w/ resected brain mets?
A
- Obs. vs. SRS
– Median OS: 18 mos vs. 17 mos; P=0.24
– 1-yr freedom from local recurrence: 43% vs. 72%; p=0.015
— 1-yr LC: 57% vs. 28%
– 1-yr freedom from local recurrence a/w # of resected mets:
— 1 Resected Met: 53%
— 2-3 Resected Mets: 62%
– In the MVA, the significant predictors of local recurrence were SRS and met size
– There were no treatment-related deaths in either group, and there was no radiographic evidence of necrosis in the SRS group.
21
Q
Per the post hoc analysis of the Mahajan et al. 2017 trial, which looked at post-op SRS vs. observation, how is resection cavity diameter size related to LC?
A
- 1-yr freedom from LR w/ respect to cavity diameter
– ≤ 2.5 cm: 91%
– 2.5-3.5 cm: 40%
– > 3.5 cm: 36%
22
Q
For targets > 3-4 cm, is SRS or SRT preferred?
A
- SRT (30/5, 24/3, etc.)
– Risk of radionecrosis is increased
– LC w/ SRS for targets > 3-4 cm is suboptimal
23
Q
Which liver met histologies are the most radiosensitive?
A
24
Q
Following SRS to the brainstem, what is the rate of severe (Gr ≥ 3) tox
A
- 7.4%
- Grade 3 tox includes:
– Local edema
– Hemorrhage
– Radionecrosis requiring medical intervention
– Encephalopathy
– Seizure
– Syncope
– Memory loss
– Ataxia impairing activities of daily living.
25
When combining WBRT w/ SRS for brain mets, by how much is it reasonable to decrease the SRS dose?
~30%
26
What were the overall results and the main conclusion of the FIRE-SCLC study looking at SRS vs. SBRT for brain mets from SCLC?
- For all pts:
-- Median OS = 8.5 months
-- Median TTCP = 8.1 months
-- Rare leptomeningeal progression (10.8%) and neurologic mortality (12.4%)
- Propensity score-matched analysis of SRS vs. WBRT
-- WBRT a/w improved TTCP (HR=0.38, p<0.001)
-- No change in OS (6.5 mos vs 5.2 mos)
- Conclusion: The results for SRS for brain metastases in SCLC are similar to those in other malignancies versus those of WBRT, namely decreased TTCP with similar OS
27
What were the results of the FIRE-SCLC study looking at SRS vs. SBRT for brain mets from SCLC when stratified by the number of brain mets?
- Median OS:
--1 lesion: 11.0 months
-- 2-4 lesions: 8.7 months
-- 5-10 lesions: 8.0 months
-- ≥ 11 lesions: 5.5 months
28
What are the components of the TEACHH prognostic model for pts referred for palliative RT?
1. **T**ype of Cancer (lung and other vs. breast and prostate)
4. **E**COG performance status (2-4 vs. 0-1)
2. Older **A**ge (>60 years vs. ≤ 60 years)
6. **C**hemotherapy, prior palliative courses (≥2 vs.<2)
3. **H**epatic metastases
5. **H**ospitalizations within 3 months before palliative RT (0 vs. ≥1)
29
How are the TEACHH prognostic model scores related to OS for metastatic pts referred for palliative RT?
30
For a pt w/ continued pain after RT for bone mets, when can re-irradiation be considered?
> 4 wks
31
How many pts will experience pain relief upon re-irradiation if they did not respond do a prior round of palliative RT for their bone met?
~ 50%
32
What doses of RT can be used to treat spinal metastases from radioresistant histologies, like RCC?
SBRT is more useful than conventional palliative RT for radioresistant histologies:
- 24 Gy in 2 fx
- 27-30 Gy in 3 fx
33
What is the rate of a flare reaction for pts undergoing conventional palliative RT for bone mets w/o steroids?
30-40%
34
What is the rate of a flare reaction for pts undergoing palliative SBRT for bone mets w/o steroids?
~60%
35
What is the rate of a flare reaction for pts undergoing single-fx palliative RT for bone mets w/o steroids?
15%
36
How can flare reaction in pts undergoing palliative bone met RT be managed?
- Steroids (dex 8 mg 1 hr prior to tx and 4 days after)
- May reduce the incidence of a flare reaction by ~10%
- May improve the time to flare reaction occurrence
37
What are the SINS criteria?
- CAPLET for SINS criteria:
-- Collapse of the vertebral body
-- Alignment of spine radiographically
-- Pain
-- Location (junctional, mobile, semi-rigid, or rigid spine)
-- Extension unilaterally or bilaterally to posterolateral spinal elements
-- Type of lesion (blastic, mixed, or lytic)
- Scores:
-- 0-6 Stable
-- 7-12 indeterminate
-- 13-18 is unstable
-- Surgical consult required ≥ 7
- HOOK: Capitol (CAPLET) Sin
38
In RTOG 9508, what were the outcomes in the WBRT vs. WBRT + SRS arm?
- 1-3 brain mets → WBRT (37.5/15) vs. WBRT+SRS (RTOG 9005 doses)
-- Median OS: 5.7 vs. 6.5 mos (NS)
-- Median OS (multiple mets): 6.7 vs. 5.8 months (NS)
-- Median OS (single met): 4.9 vs 6.5 mos (SS)
-- Stable or improved KPS at 6 mos: 27% vs. 43% (SS)
-- 1-yr LC: 71% vs. 82% (SS)
39
What is the OS survival benefit a/w using a PRO questionnaire vs. usual care for pts undergoing palliative CHT?
- 5 mos (31.2 mos vs. 26 mos)
- Anytime a patient reported new or worsening symptoms on PRO, a nurse was alerted to follow-up.
40
What are the benefits of using mindfulness-based cognitive therapy, art therapy, and stress therapy for cancer pts?
Reduces anxiety and depression
41
What are the barriers to palliative and goals of care discussions in the medical setting for the ROs?
- Not wanting to upset the medical oncologist (31%)
- Inability to schedule clinic time to hold these conversations (31%)
- Poor insurance reimbursement (12%)
- Lack of interest in this clinical area (9%)
- Other causes (17%)
42
How much can you save costs by calling an inpatient palliative care consult within 2 or 6 days of hospitalization per Project ENABLE Il, Bakitas et al. JAMA 2009?
- 2 days: 24%
- 6 days: 16%
43
What were the main findings of Project ENABLE Il, Bakitas et al. JAMA 2009?
- Advanced cancer pt → Nursing-led palliative intervention vs. usual care
- Improved QoL in the intervention group (SS)
- Resource use (days in hospital/ICU, visits to ED, etc) NS
44
What were the main findings of Project ENABLE IlI, May et al. JCO 2015?
- Advanced care → early vs. delayed supportive oncology intervention
- No change in QOL
- Improved OS at 1 yr
-- ↑15%: 48% → 63%
45
What is the rate of skeletal-related events (SRE) in high-risk asymptomatic bone mets treated w/ RT vs. observation per the recent MSKCC Phase II clinical trial?
SREs in RT vs. Obs arms:
- 1.6% vs. 29% (p=0.001)
46
What characterizes a high-risk bone lesion per the recent MSKCC Phase II clinical trial?
- High-risk
-- Diameter ≥ 2 cm
-- Location in the junctional spine
-- Involving the hip or sacroiliac joint
-- Involving one of the long bones of the body, such as those found in arms and legs.
47
What skeletal-related events were improved w/ the tx of a a high-risk bone lesion per the recent MSKCC Phase II clinical trial?
- Skeletal-related events (SREs)
-- Pain
-- Spine fractures
-- Spinal cord compression requiring surgery or radiation
48
What was the pt population, randomization, and primary EP of the SCORAD trial for malignant epidural spinal cord compression (MESCC)?
- Pt: proved dx of MSECC or cauda equina syndrome
- Randomization:
-- 8 Gy / 1 fx
-- 20 Gy / 5 fx
- Primary EP: Ambulatory status at 8 weeks
- Secondary EPs: Ambulatory status at weeks 1, 4, and 12, and OS
49
What were the results of the SCORAD trial for malignant epidural spinal cord compression (MESCC)?
- 8 Gy vs. 20 Gy:
-- Week 8 ambulatory status: 69.3% in the 8Gy vs. 72.7%; p=0.06 (non-inferiority not demonstrated)
-- Non-inferiority was demonstrated for all other secondary time points at 1, 4, and 12 weeks
-- 12 weeks OS: 50% vs. 55% (NS)
- Conclusion: While the SCORAD trial failed to meet its primary endpoint of non-inferiority of ambulatory status at 8 weeks with single-fraction RT, the clinical difference between arms was overall negligible
50
Which malignant histology demonstrates on OS benefit w/ WBRT f/b SRS boost for brain metastases per RTOG 9508?
- SqCC
- NCLC
51
What are the RPA classes for pts w/ brain metastases, and what are their respective effects on OS?
52
What is the median OS of pts w/ 1-4 brain mets (<3 cm each) that receive WBRT + SRS vs. WBRT alone per Aoyama et al, JAMA 2006?
- 7.5 mos vs. 8 mos (NS)
53
What were the findings of the Temel et al study, NEJM 2010 re: standard oncologic care w/wo early palliative care in pts w/ mNSCLC?
- At 12 weeks, the early palliative care group had
-- better QOL
-- less depressive sx
-- longer median OS (11.6 vs. 8.9 mos) despite receiving less aggressive EOL care
54
What were the findings of the RTOG 0631 trial re: SBRT (16-18Gy/1fx) vs. standard 1-fx EBRT (8/1)?
SBRT (16-18/1) vs. EBRT (8/1)
- Pain response at 3 mos: 41.3% vs. 60.5% (SS)
- Pain response at 12 mos: NS
- Rate of adverse events: NS
## Footnote
MNEMONIC: 6x3 in 1 fx (631)
55
What were the findings of the SC.24 trial (Sahgal et al, Lancet Onc 2021) re: SBRT (24Gy/2fx) vs. standard EBRT (20/5)?
SBRT (24/2) vs. EBRT (20/5)
- Pain response at 3 mos: 35% vs. 14% (SS)
- Pain response at 6 mos: 32% vs. 16% (SS)
- ≥ Gr 3 pain: 5% vs. 4% (SS)
56
What is the Bilsky scoring system for spinal cord compression?
- Grade 0: Bone involvement only
- Grade 1: Epidural impingement
- Grade 2: Spinal cord compression but CSF visible
- Grade 3: Spinal cord compression and no CS seen
57
What is Mirels criteria for pathologic fx?
Palliative, Benign, Constraints
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