Radiation Oncology/Palliation/Spinal Cord Compression

Spinal Cord Compression

• Please also see the bone metastasis page, which includes spine metastases without cord compression
• Please also see summary of randomized evidence
• Please also see the spine dose tolerance page

Epidemiology

• Estimated >20,000 cases in US per year, in ~10% patients
  • Most common breast (~30%), NSCLC (~17%), prostate (~14%)
• Clinical presentation
  • Back pain (90%), frequently for weeks
  • Weakness (80%)
  • Sensory deficits (50-80%)
  • Autonomic dysfunction (40-60%)
• Definition (Princess Margaret, see PMID 15774794)
  • Radiographic features: Compression of dural sac and its contents (spinal cord and/or cauda equina) by an extradural tumor mass. Minimum radiographic evidence is indentation of the theca at the level of clinical features
  • Clinical features: Any or all of the following: pain (local or radicular), weakness, sensory disturbance, and/or evidence of sphincter dysfunction.
• Anatomically, compression can be intramedullary, leptomeningeal, or extradural
• Pathophysiology of extradural compression includes several mechanisms
  • Continued growth of bone met into epidural space
  • Blockage of neural foramina by a paraspinal mass
  • Destruction of vertebral bone, causing a collapse and displacement of bony fragments into epidural space
  • Vascular obstruction of epidural venous plexus, leading to cord edema, ischemia, and ultimately permanent damage
• History (adapted from Perez, 4th):
  • When did the pain begin?
  • When last walking independently?
  • Why come to hospital today?
  • Fever or weight loss?
  • Last void?
• Physical exam (adapted from Perez, 4th):
  • KPS?
  • Raise legs against gravity?
  • Hands sensation compared with feet sensation?
  • Reflexes (ankle, knee, elbow, wrist)?
• Workup: MRI (sensitivity 93%, specificity 97%, accuracy 95%)
• Predictive factors: time to development of motor deficits, favorable histology
• Median OS ~3 months
  • If ambulatory after treatment, median OS ~7 months
  • If non-ambulatory after treatment, median OS ~1.5 months
  • Approximately 30% can survive >1 year

Prognosis

• Multi-national; 2008 PMID 18436390 -- "A Score Predicting Posttreatment Ambulatory Status in Patients Irradiated for Metastatic Spinal Cord Compression." (Rades D, Int J Radiat Oncol Biol Phys. 2008 Apr 22. [Epub ahead of print])
  • Scoring system. 2096 met spinal cord compression patients. Factors: primary tumor type, interval between tumor diagnosis and MSCC, visceral mets, motor function before RT, time to develop motor deficits. Total score 21-44. Outcome modeled: ambulatory status
  • Outcome: Post-RT ambulatory rate if score <=28 6%, 29-31 44%, 32-34 70%, 35-37 86%, >=38 98%. 6-month OS 6%, 31%, 42%, 61%, 93%
  • Conclusion: For patients with score <=28, suggest short course RT. For patients with score 29-37, suggest surgery + RT. For patients with score >=38 RT alone provides excellent results

• Multi-national; 2011 PMID 20605351 -- "Validation of a score predicting post-treatment ambulatory status after radiotherapy for metastatic spinal cord compression." (Rades D, Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1503-6.)
  • 653 patients (treated with RT alone) prospective trial for validation of 2008 retrospective study with 2096 patients reported above. Same scoring system as 2008 with simplified three instead of five groups for post treatment ambulatory status. RT alone groups were compared with another group of 104 patients treated with surgery followed by RT.
  • Outcome: Post-RT ambulatory rate for score ≤28 (Group I)=10.6%, 29-37 (Group II)=70.9%, ≥38 (Group III)=98.5%. 6-month OS 11.3%, 46.4%, and 92.0%. Addition of laminectomy (n=41) did not add statistically significant (SS) benefit compared to RT alone. SS benefit with laminectomy plus stabilization (n=63) followed by RT when all groups combined (P=0.04), with non-SS trend in Group II (P=0.23, possibly due to only 31 patients in the group).
  • Conclusion: For patients with score ≤28, suggest short course RT for palliation of pain. For patients with score 29-37, consider adding laminectomy plus stabilization to RT. For patients with score ≥38 RT alone provides excellent results

• Hannover; 2002 (1998-2000) PMID 12095565 -- "Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. (Rades D, Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):975-9.)
  • Prospective. 98 patients. No surgery, dexamethasone 32-40 mg/qd. 3 subgroups based on time of motor deficit development prior to RT: Group A (1-7 days, n=31), Group B (8-14 days, n=31), and Group C (>14 days, n=36). Groups balanced. RT started as soon as possible, 30/10 or 37.5/15 or 40/20, using PA field
  • Outcome: Initial ambulatory rate A 48% vs. B 55% vs. C 56%. Post-treatment ambulatory rate 35% vs. 55% vs. 86%. This held at 6 weeks (SS), 12 weeks (SS), and trend at 24 weeks (p=0.07). Deterioration worst in Group A (10% improved, 42% stabilized, 48% worse)
  • Predictors: time-to-develop motor deficit (slower better), type of tumor (favorable=myeloma, lymphoma, SCLC, testicular better), pretreatment ambulation (ambulation better)
  • Conclusion: Functional outcome better with slower development of motor deficits before RT

Steroids

• If clinical suspicion is high, should be administered even before radiographic diagnosis. They can be rapidly discontinued if necessary
• A randomized trial showed improved ambulation with administration of steroids over no steroids, with a dose of 96 mg QD
• Loading and maintenance dose are not well established. A small randomized trial showed statistical equivalence between dexamethasone 100 mg IV and dexamethasone 10 mg, although there was a suggestion of clinical benefit for the higher dose
• Very high doses (~100 mg QD) can result in significant toxicity, and are typically not used now. One ought to be cautious in patients with diabetes mellitus, HTN, and peptic ulcer disease
• A recommended regimen (Perez 5th ed) is dexamethasone 10 mg IV loading dose, then dexamethasone 4-6 mg every 6-8 hours. Patients should also be started on proton pump inhibitor for the duration of dexamethasone based on PPI date in NSAIDs and GI prophylaxis
• A Phase II trial suggests that for patients with good motor function, corticosteroids may not be necessary, as long as they are counseled about development of symptoms

• Perugia; 1996 (Italy)(1991-1993) PMID 8610645 -- "Radiotherapy without steroids in selected metastatic spinal cord compression patients. A phase II trial." (Maranzano E, Am J Clin Oncol. 1996 Apr;19(2):179-83.)
  • Phase II. 20 patients with spinal cord compression, no neurologic deficit (radiculopathy allowed), no massive invasion of spine on MRI/CT. Walking deficits in 4 patients (2 radiculopathy, 2 back pain). No steroids given RT 30/10
  • Outcome: 100% ambulatory at completion. Median OS 14 months
  • Conclusion: RT without steroids is feasible in patients with good motor function and avoids toxicity

• Copenhagen -- 96 mg dexamethasone vs. control
  • Randomized. 57 patients with spinal cord compression. Arm 1) high-dose dexamethasone (IV bolus 96mg, then 96 mg x3 days, then 10 day taper) vs. Arm 2) no steroids
  • 1994 PMID 8142159 -- "Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial." (Sorensen S, Eur J Cancer. 1994;30A(1):22-7.)
    • Outcome: Gait function dexamethasone 81% vs. control 63%, 6-months later 59% vs. 33%. Median OS no difference
    • Toxicity: Significant side effects 11%
    • Conclusion: High-dose glucocorticoid therapy should be given as adjunct

• Norwegian Radium Hospital; 1992 PMID 1560260 -- "High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression." (Heimdal K, J Neurooncol. 1992 Feb;12(2):141-4.)
  • Retrospective. 28 consecutive patients, treated with high-dose dexamethasone (96 mg IV, taper in 14 days).
  • Toxicity: 29% side-effects, 14% serious (1 fatal ulcer, 1 rectal bleeding, 1 GI perforation, 1 sigmoid perforation)
  • Conclusion: High incidence of side effects, now use dexamethasone 16 mg daily, taper in 14 days

• Rotterdam -- bolus 10 mg IV vs. bolus 100 mg IV
  • Randomized. 37 patients with cord compresion. Arm 1) Dexamethasone bolus 10 mg IV vs. Arm 2) dexamethasone bolus 100 mg IV. Both followed by dexamethasone 16 mg daily
  • 1989 PMID 2771077 -- "Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression." (Vecht CJ, Neurology. 1989 Sep;39(9):1255-7.)
    • Outcome: Improved neurologic status: moderate 8% vs. high 25% (NS). Overall no difference in pain, ambulation, or bladder function
    • Conclusion: No difference
    • Comment: Small trial, and clinically significant difference (8% vs. 25%) if real

Surgery + RT vs. RT alone

• Surgery is indicated when there is spinal instability or bony retropulsion causing the cord compression. This is a consensus opinion, without literature support (see PMID 15774794)
• Surgery may also be indicated in patients with symptomatic cord compression, with paralysis <2 days based on the Patchell trial. However, there is significant morbidity associated with the operation, and the trade-offs need to be considered. Laminectomy doesn't appear as beneficial

• Bluegrass Neuro-Oncology Consortium (1992-2002) -- Decompression + RT vs. RT alone
  • Randomized. Stopped early after meeting stopping rule. 101/200 patients, paraplegia <=48 hours. Spinal cord compression from mets (excluded radiosensitive histologies, CNS primary). Decadron 100 mg, then 24 mg Q6. Arm 1) Surgery + RT vs. Arm 2) RT alone. 32 unable to walk (16 vs. 16). RT 30/10, field 8cm wide and one VB above/below lesion. RT started within 14 days post-op, or within 24 hrs of randomization. Endpoint ability to walk.
  • 2005 PMID 16112300 -- "Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial." (Patchell RA, Lancet. 2005 Aug 20-26;366(9486):643-8.)
    • Ability to walk: surgery + RT 84% vs. RT alone 57% (SS). Length of response: 122 days vs. 13 days (SS). No improvement: surgery + RT 19% vs. RT alone 62% (SS)
      • If ambulatory: Ability to walk 94% vs. 74% (SS); duration of response 153 days vs. 54 days (SS)
      • If non-ambulatory: Ability to walk 62% vs. 19% (SS); duration of response 59 days vs. 0 days (SS)
    • Cross-over: ambulatory patients treated with RT alone and failed, then treated with surgery: 30% able to walk
    • Continence: surgery + RT 156 days vs. RT alone 17 days (SS); OS 126 days vs. 100 days (SS)
    • Conclusion: Direct decompression + RT better than RT alone, even for patients who are ambulatory
  • Comment: RT alone arm results significantly worse than what would have been expected based on other prospective RT trials; took 10 yrs to accrue 101 pts, suggesting results apply to only a minority of cord compression pts; non-neurologic morbidity higher in RT alone group, suggesting insufficient stratification factors used

• Germany (2000-2009)
  • 2010 PMID 20606090 --"Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression (Rades D, J Clin Oncol. 2010 Aug 1;28(22):3597-604)
  • Matched pair analysis of 108 pts receiving surgery+ steroids + RT for metastastic cord compression vs 216 pts (1:2 match) from database of 2300 pts treated w/ RT alone. Matched for 11 potential prognostic factors. Included pts w/ multiple involved vertebrae, myeloma/lymphoma, non-ambulatory pts.
    • Outcomes (RT alone vs surg RT--no p values significant)
      • Ambulatory Post-Treatment: 68% vs 69%
      • Regained Ambulation: 26% vs 30%
      • 1 yr local control: 91% vs 90%
      • 1 yr OS: 40% vs 47%
      • Complications: None > CTCAE gr. 1 vs 11% sig bleed, postop pneumonia, PE
  • Conclusion: Endpts after RT alone similar to surg+ RT. A new RCT is justified.

• Upstate, New York -- Laminectomy +RT vs. RT alone
  • 1980 PMID 7441333 -- "Treatment of spinal epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy." (Young RF, J Neurosurg. 1980 Dec;53(6):741-8.)
  • Randomized. 29 patients, metastatic spinal cord compression. Arm 1) laminectomy + RT vs. Arm 2) RT alone. Post-op RT started within 7 days, 30/10, +/- one VB using single PA field at 5 cm depth. RT alone 12/3 followed by 18/7, started within 1-2 after myelogram. Decadron IV 12 mg loading, then 4 mg Q6.
    • Outcome: No difference in pain relief (88% vs. 92%), improved ambulation (45% vs. 54%), or sphincter function. Mean survival 6 months vs. 5 months (NS).
    • Conclusion: Results are suggestive but not conclusive due to limited size and design defects

RT Dose

• There does not appear to be any difference among the various dose-fractionation regimens
• In the US, RT 30/10 is considered standard of care, and shorter fractionation schedules (20/5 or 8/1) are typically reserved for those with progressive disease refractory to systemic chemotherapy and are typically avoided in newly diagnosed patients who are chemotherapy-naive (Perez 5th ed)
• German multi-institutional randomized trial showed 20/5 schema is not inferior to 30/10 schema, in patients with poor/intermediate survival

• SCORE-2 / ARO 2009/01 -- epidural spinal cord compression, 20/5 vs 30/10
  • Randomized. 203 patients with metastatic spinal cord compression, lower extremity motor deficits. Evaluated by neurosurgeon. Poor or intermediate prognosis (score <=38 points on scoring system (above)). Diagnosis confirmed by MRI. Arm 1) 4 Gy x 5 fractions vs Arm 2) 3 Gy x 10 fractions. 3D-conformal ~70%, rest PA or AP/PA fields. Primary end point motor deficits at 1 month
  • Results, 2016 PMID 26729431 -- Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01)." (Rades D, J Clin Oncol. 2016 Feb 20;34(6):597-602. doi: 10.1200/JCO.2015.64.0862. Epub 2016 Jan 4.)
    • Outcome: 1 month response rate 4x5 87% vs 3x10 90% (NS). Improvement 38% vs 44% (NS), stable function 49% vs 45%, further deterioration 13% vs 10% (NS for all). Ambulatory rate 72% vs 78% (NS). 6-month LC 75% vs 82% (NS)
    • Conclusion: Short course RT with 4 Gy x 5 was not inferior to 3 Gy x 10 in these patients

• Germany / Netherlands; 2008 (2006-2008) PMID 18539406 -- "Preliminary Results of Spinal Cord Compression Recurrence Evaluation (Score-1) Study Comparing Short-Course Versus Long-Course Radiotherapy for Local Control of Malignant Epidural Spinal Cord Compression." (Rades D, Int J Radiat Oncol Biol Phys. 2008 Jun 6. [Epub ahead of print])
  • Prospective, 2 arm. 231 patients with spinal cord compression. Arm 1) Short RT (8/1, 20/5) or Arm 2) Long RT (30/10, 37.5/15, or 40/20). Randomization not possible as different schedules used for logistical reasons in different countries. Primary endpoint PFS (lack of progressive motor deficits or in-field recurrence)
  • Outcome: 12 month PFS short RT 55% vs. long RT 72% (SS); LC 61% vs. 77% (SS); OS 25% vs. 32% (NS). Improvement in motor function 28% vs. 30% (NS)
  • Conclusion: Short and long course RT similar functional outcome and OS. However, long course RT significantly better for PFS and LC

• Multi-national (1992-2003)
  • NSCLC; 2006 PMID 16580192 -- "Defining the appropriate radiotherapy regimen for metastatic spinal cord compression in non-small cell lung cancer patients." (Rades D, Eur J Cancer. 2006 May;42(8):1052-6.)
    • Retrospective. 252 NSCLC patients with SCC compression. Treated with short (8/1 or 20/5) or long (30/10, 37.5/15, or 40/20) RT. Improvement in motor function 14%, no change 54%, deterioration 32%
    • Oucome: function affected by time of motor deficit before RT (>14 days better). No impact of RT regimen. In short RT group, no difference between 8/1 and 20/5
    • Conclusion: recommend 8 Gy x 1
  • Multiple myeloma; 2006 PMID 16413695 -- "Short-course radiotherapy is not optimal for spinal cord compression due to myeloma." (Rades D, Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5):1452-7.)
    • Retrospective. 172 patients. Treated with short (8/1 or 20/5) or long (30/10, 37.5/15, or 40/20) RT
    • Outcome: Improvement in 52%; in nonambulatory 47% regained ability to walk. Improvement more frequent after long-course RT 76% vs. 40% (SS) at 1 year, 83% vs. 54% (SS) at 2 years. Similar outcome among the different long fractionation schemes
    • Conclusion: Long-course RT preferable for myeloma patients; 30/10 appropriate
  • Fractionation; 2005 PMID 15908648 -- "Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression." (Rades D, J Clin Oncol. 2005 May 20;23(15):3366-75.)
    • Retrospective. 1304 patients with spinal cord compression. Treated with 8/1, 20/5, 30/10, 37.5/15, 40/20
    • Outcome: motor function improved in ~30%, ambulatory rates ~70%. RT schedule not associated with outcome. Recurrence rates: 8/1 24%, 20/5 26%, 30/10 14%, 37.5/15 9%, 40/20 7% (SS); no difference between 8/1 and 20/5, and no difference between 30/10, 37.5/15, and 40/20
    • Toxicity: acute mild (Grade I only), no late toxicity
    • Conclusion: Similar functional outcome. Recommend 8/1 in expected poor survival, and 30/10 in expected good survival

• Germany / Netherlands; 2005 (1999-2003) - PMID 15890595 — "Comparison of 1 x 8 Gy and 10 x 3 Gy for functional outcome in patients with metastatic spinal cord compression." Rades D et al. Int J Radiat Oncol Biol Phys. 2005 Jun 1;62(2):514-8.
  • Retrospective. 96 pts treated 1 x 8 Gy (in Amsterdam) compared with 108 pts treated with 10 x 3 Gy (in Germany). Evaluated ambulatory status and motor function
  • No difference in outcome between the two radiation regimens. 1 x 8 Gy should be considered in poor prognosis patients.

• Italy (1998-2002) -- 16/2 (over 1 week) vs. 15/3 + 15/5 (over 2 weeks)
  • Randomized. 300 patients, short life expectancy (<=6 months), with metastatic spinal cord compression. Dexamethasone 8 mg IV BID, taper after end of RT. Arm 1) Short-course RT (8 Gy x 2 over 7 days) vs Arm 2) Split-course RT (5 Gy x 3, 4 day break, 3 Gy x 5). RT 2 VBs above and below.
  • 2005 PMID 15738534 — "Short-Course Versus Split-Course Radiotherapy in Metastatic Spinal Cord Compression: Results of a Phase III, Randomized, Multicenter Trial." (Maranzano E et al. J Clin Oncol. 2005 May 20;23(15):3308-10.)
    • Outcome: Pain relief short 56% vs long 59% (NS), ambulation 68% vs. 71% (NS), bladder function 90% vs. 89% (NS). Median OS 4 months. Recurrence 2%, all in short course
    • Toxicity: Grade 1-2 dysphagia 14%, Grade 1-2 diarrhea 7%
    • Conclusion: Both regimens effective, short-course more convenient for patients

• "Always on a Friday", Netherlands, 2001 (1987-97)
  • PMID 11321668 — "Always on a Friday? Time pattern of referral for spinal cord compression." Poortmans P et al. Acta Oncol. 2001;40(1):88-91.
  • 443 pts treated for spinal cord compression. 30% of referrals took place on Fridays.

Specific tumor types

Myeloma:

• For more information on treatment of spinal cord compression, see Radiation Oncology/Multiple myeloma.

Re-treatment

• Please also see spine NTCP page; Radiation_Oncology/Palliation/Bone_metastases#Re-treatment

• Multi-national; 2008 (1995-2007) PMID 18642349 -- "Prognostic factors for functional outcome and survival after reirradiation for in-field recurrences of metastatic spinal cord compression." (Rades D, Cancer. 2008 Jul 18. [Epub ahead of print])
  • Retrospective. 124 patients re-irradiated for MSCC in-field recurrence, C-spine excluded. First RT 8/1 or 20/5 or 30/10 or 37.5/15 or 40/20 depending on medical center. All stable/improved after first RT. All motor deficits at time of Re-RT, 69% ambulatory. Second RT 8/1 (38%), 15/5 (23%), 20/5 (24%), 21/7 (2%), 20/10-24/12 (9%). Cummulative BED(a/b=2) 77.5-143 Gy, 92% <=120 Gy. Median F/U 11 months
  • Outcome: Motor function improved 36%, stable 50%, deteriorated 14%. Predictors for motor function: effect of 1st RT, ECOG PS, time-to-motor deficits, visceral mets. Re-RT dose or cumulative BED no impact on function or OS
  • Late toxicity: No radiation myelopathy observed
  • Conclusion: Spinal irradiation appears effective and safe when cumulative BED <120 Gy (a/b=2, corresponds to 60 Gy in 2 Gy/fx). Single fraction reasonable if poor estimated survival

• Hamburg, 2005 (Germany)(1995-2003) PMID 16170487 -- "[Effectiveness and toxicity of reirradiation (Re-RT) for metastatic spinal cord compression (MSCC)]" - [Article in German] (Rades D, Strahlenther Onkol. 2005 Sep;181(9):595-600.)
  • Retrospective. 74 patients re-irradiated in-field. Median F/U 9 months
  • Outcome: Improved motor function in 39%; no impact of RT schedule, cumulative EQD2, or time between treatments
  • Toxicity: no radiation myelopathy. Cumulative EQD2 (using a/b=2) 39-40 in n=21, 49-50 in n=41, 56-60 in n=6, and >60 in n=6
  • Conclusion: Re-RT effective for in-field recurrence of cord compression

• Knoxville, TN; 2005 PMID 16125871 -- "Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis." (Mahan SL, Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1576-83. Epub 2005 Aug 26.)
  • Retrospective. 8 patients with spinal cord compression after prior RT (30/10 - 45/25 Gy). Tomotherapy technique. Retreatment dose 20-30 Gy in 2-2.5 Gy/fx. Cummulative spinal cord Dmax limit 50 Gy. Dose gradient 10%/mm. Mean F/U 15 months
  • Outcome: 100% LC. Complete pain relief 6/8, partial pain relief 2/8
  • Complications: None
  • Conclusion: Tomotherapy

Guidelines and Standards

• Johns Hopkins; 2008 PMID 18688056 -- "Evidence-based standards for cancer pain management." (Dy SM, J Clin Oncol. 2008 Aug 10;26(23):3879-85.)
  • Literature review, then expert panel. Metastatic bone pain and spinal cord compression
  • Spinal cord compression: MRI imaging. Corticosteroids. Start definitive treatment (surgery or RT) within 24 hours

• Toronto; 2005 PMID 15774794 -- "Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group." (Loblaw DA, J Clin Oncol. 2005 Mar 20;23(9):2028-37.)
  • Minimize treatment delay. MRI imaging. High dose dexamethasone effective, but significant toxicity. Patients who are ambulatory do not need dexamethasone, but should be educated about the symptoms of spinal cord compression
  • Treatment for patients with MSCC should consider pretreatment ambulatory status, comorbidities, technical surgical factors, the presence of bony compression and spinal instability, potential surgical complications, potential RT reactions, and patient preferences.

• Toronto; 1998 PMID 9552073 -- "Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline." (Loblaw DA, J Clin Oncol. 1998 Apr;16(4):1613-24.)