“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,” posited the study authors. Therefore, the researchers questioned “whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy.”
The findings of the study—a multicenter, noninferiority, randomized clinical trial—were published in JAMA.
The study took place at 42 UK and five Australian radiotherapy centers and included 686 metastatic cancer patients with spinal cord or cauda equina compression, who were recruited from February 2008 through April 2016. Other eligibility criteria included life expectancy greater than eight weeks and no history of radiotherapy to the same area. Final follow-up was performed in September 2017. Patients randomly received either external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in five fractions over five consecutive days (n = 341). The primary outcome measure was eight-week ambulatory status per a four-point scale, with grade 1 defined as “ambulatory without the use of aids and grade 5 of 5 muscle power” and grade 2 as “ambulatory using aids or grade 4 of 5 muscle power.” The authors classified the noninferiority margin for the ambulatory status difference as –11%. Other outcomes were one-, four-, and 12-week ambulatory status, as well as overall survival.
Of the initial 686 patients who were randomized (median [interquartile range] age, 70 [64 to 77] years; 503 [73%] were male), most (44%) had prostate cancer; 19% had lung cancer and 12% had breast cancer. In total, 255 patients died prior to the eight-week assessment. Just about half of the total initial cohort (n = 342, 49.8%) was analyzed for the primary outcome. Of the patients available for analysis, in the single-fraction group (n = 166), eight-week ambulatory status grade 1 or 2 was attained by 115 patients (69.3%); 176 patients in the multifraction group were available for eight-week analysis, of whom 128 (72.7%) achieved ambulatory status grade 1 or 2 (difference, −3.5% [one-sided 95% CI, −11.5% to ∞]; P value for noninferiority = 0.06). Regarding the secondary outcomes, the study authors reported: “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.” The 12-week overall survival rate was lower in the single-fraction group than the multifraction group (50% vs. 55%; stratified hazard ratio, 1.02 [95% CI, 0.74 to1.41]). Other secondary outcomes did not largely differ between the groups or did not meet noninferiority criterion.
“We believe our findings, which show equal clinical effectiveness for single-dose radiotherapy, provide strong evidence for [National Institute for Health and Care Excellence] guidelines, and those in other countries, to be changed to stipulate a one-dose one-visit approach, reducing unnecessary discomfort for end of life cancer patients without compromising efficacy,” said lead study investigator professor Peter Hoskin, of the University of Manchester, Mount Vernon Cancer Centre (NHS), in a press release.