Radiation Oncology/Palliation/Spinal Cord Compression/Randomized

Spinal Cord Compression Randomized Evidence

Steroids

• 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

• 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

• Bluegrass Neuro-Oncology Consortium (1992-2002) -- Surgery + RT vs. RT alone
  • Randomized. Stopped early after meeting stopping rule. 101 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.
  • 2008 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

RT Dose

• 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