Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression

Br J Cancer. 2020 Apr;122(9):1315-1323. doi: 10.1038/s41416-020-0768-z. Epub 2020 Mar 11.

Abstract

Background: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.

Methods: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms.

Results: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093).

Conclusion: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.

Clinical trial registration: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

Publication types

  • Clinical Trial, Phase III
  • Pragmatic Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dose Fractionation, Radiation*
  • Female
  • Humans
  • Ireland / epidemiology
  • Male
  • Middle Aged
  • Radiotherapy / adverse effects
  • Risk Factors
  • Spinal Cord Compression / pathology
  • Spinal Cord Compression / radiotherapy*
  • Spinal Cord Neoplasms / pathology
  • Spinal Cord Neoplasms / radiotherapy*
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT00968643