[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.207.240.35. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 7,633
Citations 0
Original Investigation
December 3, 2019

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial

Author Affiliations
  • 1Mount Vernon Cancer Centre, Northwood, United Kingdom
  • 2University of Manchester, Manchester, United Kingdom
  • 3Bristol Centre for Haematology and Oncology Bristol, Bristol, United Kingdom
  • 4The Christie Hospital, Manchester, United Kingdom
  • 5Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
  • 6The Freeman Hospital, Newcastle, United Kingdom
  • 7Queen Alexandra Hospital, Portsmouth, United Kingdom
  • 8Royal Sussex County Hospital, Brighton, United Kingdom
  • 9Weston Park Hospital, Sheffield, United Kingdom
  • 10Southend University Hospital, United Kingdom
  • 11Raigmore Hospital, Inverness, United Kingdom
  • 12Southampton General Hospital, Southampton, United Kingdom
  • 13The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
  • 14Velindre Cancer Centre, Cardiff, United Kingdom
  • 15Kent Oncology Centre, Maidstone, United Kingdom
  • 16Royal Adelaide Hospital, Adelaide, Australia
  • 17University of Adelaide, Adelaide, Australia
  • 18Castle Hill Hospital, Hull, United Kingdom
  • 19CRUK & UCL Cancer Trials Centre, London, United Kingdom
JAMA. 2019;322(21):2084-2094. doi:10.1001/jama.2019.17913
Visual Abstract.
Visual Abstract.
Single-Fraction vs Multifraction Radiotherapy and Ambulatory Status in Spinal Canal Compression Due to Metastatic Cancer
Single-Fraction vs Multifraction Radiotherapy and Ambulatory Status in Spinal Canal Compression Due to Metastatic Cancer
Key Points

Question  Is treatment with a single dose of radiotherapy noninferior to multifraction radiotherapy delivered over 5 days among patients with metastatic cancer who have spinal canal compression?

Findings  In a clinical trial of 686 patients, the percentage who were ambulatory at 8 weeks was 69.3% in the single-fraction group vs 72.7% in the multifraction radiotherapy group. The lower CI limit for the risk difference (−11.5%) did not meet the predefined noninferiority margin of −11.0%.

Meaning  Treatment with single-fraction radiotherapy did not meet the criterion for noninferiority compared with multifraction radiotherapy for ambulatory response rate at 8 weeks, but consideration should be given to the extent to which the lower bound of the CI overlapped with the noninferiority margin.

Abstract

Importance  Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen.

Objective  To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy.

Design, Setting, and Participants  Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017.

Interventions  Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341).

Main Outcomes and Measures  The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was −11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival.

Results  Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, −3.5% [1-sided 95% CI, −11.5% to ∞]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was −0.4% (63.9% vs 64.3%; [1-sided 95% CI, −6.9 to ∞]; P value for noninferiority = .004) at week 1, −0.7% (66.8% vs 67.6%; [1-sided 95% CI, −8.1 to ∞]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, −4.6 to ∞]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion.

Conclusions and Relevance  Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding.

Trial Registration  ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008

×