1. Radiotherapy for Metastatic Spinal Cord Compression
Dirk Rades, MD
Professor and Chair
Department of Radiation Oncology
University of Lübeck, Germany

2. Metastatic Spinal Cord Compression
MSCC in 5-10%
of all cancer patients
most common primaries:
Breast-Ca (~25%)
Prostate-Ca (~20%)
Lung-Ca (~20%)
Myeloma (10-15%)
Renal Cell Cancer (~10%)
Localization:
cervical <10%
thoracic 60-80%
lumbar 15-30%
Prasad et al. Lancet Oncol 2005
Lesion of
dorsal elements
Lesion of vertebra

3. “True“ MSCC = Motor Deficits
=> Poor Survival Prognosis
Year N pts. Median OS (mos.)
Sorensen et al
Helweg-Larsen et al
Rades et al
Hoskin et al
Maranzano et al
Overall Treatment Time ?

4. Evaluation of five radiation schedules and prognostic factors for MSCC
in a series of 1,304 patients
Schedule Time N Pts.
1 x 8 Gy 1 day 261
5 x 4 Gy 1 week 279
10 x 3 Gy 2 weeks 274
15 x 2.5 Gy 3 weeks 233
20 x 2 Gy 4 weeks 257
Rades et al., JCO 2005

5. Improvement of Motor Deficits

6. Particularly important for long-term survivors !
SCORE-1: Long-course (10x3 Gy, 15x2.5 Gy, 20x2 Gy) vs. Short-course RT (1x8 Gy, 5x4 Gy)
Particularly important for long-term survivors !
Rades et al., ASCO IJROPB 2011

7. Survival-Score (N=1,852) Rades et al., Cancer 2008
at 6 months (%)
Score
Type of primary tumor
Breast cancer
Prostate cancer
Myeloma/lymphoma
Lung cancer
Other tumors 78 66 85 25 40 8 7 9 3 4
Other bone metastases
Yes No 48 65 5
Visceral metastases 17 80 2
Interval tumor diagnosis to MSCC
15 months
>15 months 41 71
Ambulatory status
Ambulatory
Non-ambulatory 31
Time of developing motor deficits
1-7 days
8-14 days
>14 days 26 55 6
Rades et al., Cancer 2008

8. 5x4 Gy vs. 10x3 Gy (randomized SCORE 2 - Trial)
Rades et al., JCO 2016

9. 5x4 Gy vs. 10x3 Gy (randomized SCORE 2 - Trial)
Rades et al., JCO 2016

10. Matched-Pairs (N=242): 1x8 Gy vs. 5x4 Gy (≤35 points)
Rades et al., IJROBP 2015

11. Matched-Pairs (N=410): 1x8 Gy vs. 5x4 Gy (all patients)
Matched-Pair Analysis (1:1):
(age, gender, ECOG, tumor, N vertebrae, bone mets, visc. mets, interval FD-MSCC, ambulatory st., time developing motor deficits)
Local Control of MSCC
Overall Survival
Rades et al., unpublished

12. In addition to RT: Corticosteroids
Effective ? => Yes Appropriate Dose ??

13. SCORE-1 Study: Bisphosphonates
Rades et al., IJROBP 2011

14. In addition to RT: Decompressive Surgery
surgery plus 10 x 3 Gy (N=50) vs. 10 x 3 Gy alone (N=51)
ability to walk after treatment: 42/50 (84%) vs. 29/51 (57%) p=0.001
maintaining ambulatory status: median 122 vs. 13 days p=0.003
overall survival: median 4.2 vs. 3.3 months p=0.033
Surgery only for selected patients (10-15%):
KPS  70, OS  3 mos., no paraplegia > 48 hrs., 1 spinal segment, no myeloma
10 years to accrue (not all eligible patients included ?)
10% more ambulatory patients than in other series
small number of patients (statistical power ?)
surgery-related complications: primary 12%; salvage 40%
Patchell et al., Lancet 2005

15. Surgery + RT vs. RT alone [N=324] Matched-Pair Analysis (1:2):
(age, gender, ECOG, tumor, N vertebrae, bone mets, visc. mets, interval FD-MSCC, ambulatory, time developing motor deficits, RT)
S + RT RT alone P
better motor function 27% 26%
1-year local control 90% 91%
1-year survival 47% 40%
Rades et al., JCO, 2010

16. Recurrence after Short-course RT
Re-RT for MSCC (appears safe, if BED120 Gy2)
Rades et al., IJROBP 2005, CANCER 2008

17. Recurrence after Long-course RT Surgery, if possible and indicated

18. Recurrence after Long-course RT
- if Surgery is not possible -
Re-RT ? => high precision RT
Also an Option for Less Radiosensitive Tumors ?

19. Less Radiosensitive Tumors
Dose Escalation
Rades et al., IJROBP, 2011

20. Less Radiosensitive Tumors: RS/SBRT

21. RS/SBRT: Late Toxicity - Vertebral Fractures
Yamada, IJROBP 2008 N=93 IG-IMRT 1 x 24 ( ) Gy 2%
(EQD2 = 82 – 141 Gy)
Rose, JCO 2009 N=62 IG-IMRT 1 x 24 ( ) Gy 39%
Garg, Cancer 2012 N=61 RS 1 x Gy 21%
(EQD2 = 66 – 141 Gy)
Jawad, JNS 2016 N=594 RS/SBRT median 1 x 20 Gy 6%
(EQD2 = 100 Gy)
Chang, Spine 2016 review of 38 studies 14%

22. RS / SBRT: Spinal Cord Tolerance
RTOG 06-31: Dose Constraints for SF-RS:
Spinal cord 5-6 mm cranial / caudal to target:
10% < 10 Gy
0.35 ml < 10 Gy
0.035 ml < 14 Gy
Cauda equina:
5 ml < 14 Gy
0.035 ml < 16 Gy
Sahgal et al., IJROBP 2010:
1 x 10 Gy (EQD2: 30 Gy) = safe
Kirkpatrick et al., IJROBP 2010:
1 x 13 Gy (EQD2: 49 Gy)
3 x 6.7 Gy (EQD2: 43 Gy)
risk of myelopathy <1%

23. (multidisciplinary evaluation)
MSCC
(multidisciplinary evaluation)
surgery indicated
and possible
Surgery not indicated / not possible
intermediate radiosensitivity
very radiosensitive tumors
(lymphoma, myeloma, germ cell tumors)
less radiosensitive tumors
SBRT ?
(studies)
prognosis
≤2 months
prognosis
3-6 months
prognosis
>6 months
systemic therapy?
surgery + long-course RT
[Corticosteroids,
Bisphosphonates]
SBRT
[Corticost.,
Bisphosph.]
Single Fraction
[Corticosteroids]
or BSC
Short-course RT
[Corticosteroids]
Long-course RT
[Corticosteroids,
Bisphosphonates]
Patients with MSCC require an individual (personalized) treatment approach !

24. Thank You Very Much for your Attention and Best Regards from Lübeck !