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

Pierre G Thirion, Mary T Dunne, Paul J Kelly, Aileen Flavin, Joe M O'Sullivan, Dayle Hacking, Wojciech Sasiadek, Cormac Small, Maeve M Pomeroy, Joseph Martin, Orla McArdle, Imelda Parker, Lydia S O'Sullivan, Aoife M Shannon, Angela Clayton-Lea, Conor D Collins, Michael R Stevenson, Alberto Alvarez-Iglesias, John G Armstrong, Michael Moriarty, Pierre G Thirion, Mary T Dunne, Paul J Kelly, Aileen Flavin, Joe M O'Sullivan, Dayle Hacking, Wojciech Sasiadek, Cormac Small, Maeve M Pomeroy, Joseph Martin, Orla McArdle, Imelda Parker, Lydia S O'Sullivan, Aoife M Shannon, Angela Clayton-Lea, Conor D Collins, Michael R Stevenson, Alberto Alvarez-Iglesias, John G Armstrong, Michael Moriarty

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. CONSORT flow diagram.
Fig. 1. CONSORT flow diagram.
ICORG 05-03 CONSORT flow diagram of two radiation schedules in malignant spinal cord compression.

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