Single-fraction radiation could not be shown to be noninferior to multi-fraction radiation at improving walking function in patients with spinal compression from metastatic cancer, but the small differences seen in a noninferiority trial may not matter to patients, investigators suggest.
Among 686 patients with spinal compression from metastatic cancer randomly assigned in a clinical trial to receive either 8 Gy of radiation in a single fraction or 20 Gy delivered in 5 fractions over 5 consecutive days, 69.3% of patients in the single-fraction arm had good ambulatory status at 8 weeks, compared with 72.7% of patients in the multi-fraction arm (P for noninferiority = .06), reported Peter J Hoskin, BSc, MBBS, MD, of Mount Vernon Cancer Centre in Northwood, England, and colleagues.
The trial did not meet the endpoint of noninferiority of single-fraction radiation for improving ambulation at 8 weeks because the lower limit of the 95% confidence interval (CI) was –11.5%, overlapping the noninferiority margin of –11%.
“However, for all other time points, the CI limits were within the noninferiority margin, and the observed risk differences between single-fraction and multi-fraction radiotherapy groups in ambulatory status were small and unlikely to be of clinical importance,” the investigators wrote in JAMA.
The authors note that although radiotherapy is widely used as a palliative measure for patients with spinal canal compression caused my metastatic disease, there is no agreement on the optimum schedule, with some guidelines recommending higher doses in multiple fractions, and others recommending a single 8 Gy does for patients with painful spinal sites.
To see whether single-fraction radiation could be noninferior to multi-fraction, the investigators enrolled patients in 42 sites in the United Kingdom and 5 in Australia into the SCORAD trial, and randomly assigned them to either single-fraction (345 patients) or multi-fraction (341 patients) radiation. The median age of those enrolled was 70 years, and 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer.
As noted, the primary endpoint of noninferiority of single-fraction radiation at improving ambulatory status at week 8 was not met. Ambulatory status was based on a 4-point scale and was classified as either grade 1: ambulatory without the use of aids and grade 5 of 5 of muscle power, or grade 2: ambulatory with aids or grade 4 of 5 of muscle power.
An analysis of secondary endpoints showed that the difference in ambulatory status grade 1 or 2 in the single- vs. multi-fraction group at week 1 was −0.4% (P value for noninferiority = .004), at week 4 it was −0.7% (P value for noninferiority = .01), and at week 12 it was 4.1% (P value for noninferiority = .002).
Overall survival rates at 12 weeks were 50% in the single-fraction group vs. 55% in the multi-fraction group; this difference was not statistically significant.
Of 11 other secondary endpoints analyzed, including ambulatory and safety endpoints, the between-group differences were not statistically significant or did not meet noninferiority criteria, the authors noted.
They concluded that although the trial did not meet the primary endpoint, ”the extent to which the lower bound of the CI overlapped with the noninferiority margin should be taken into account when interpreting the clinical importance of these findings.”
Cancer Research UK and Cancer Council Queensland funded the trial. Dr. Hoskin reported being supported by the National Institute for Health Research Manchester Biomedical Research Centre.
SOURCE: Hoskin PJ et al. JAMA 2019 Dec 3. doi: 10.1001/jama.2019.17913.