Effect of single-fraction vs multifraction radiotherapy on ambulatory status among patients with spinal canal compression from metastatic cancer: The SCORAD randomized clinical trial
AuthorsHoskin, Peter J
AffiliationMount Vernon Cancer Centre, Northwood, United Kingdom
MetadataShow full item record
AbstractIMPORTANCE: 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.
CitationHoskin PJ, Hopkins K, Misra V, Holt T, McMenemin R, Dubois D, et al. Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial. Jama. 2019;322(21):2084-94.
- Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial.
- Authors: Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O'Connor T, Velasco MR Jr, Weckstein D, O'Mara A, Loprinzi CL, Shapiro CL
- Issue date: 2017 Jan 3
- Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II): The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial.
- Authors: Siva S, Bressel M, Mai T, Le H, Vinod S, de Silva H, Macdonald S, Skala M, Hardcastle N, Rezo A, Pryor D, Gill S, Higgs B, Wagenfuehr K, Montgomery R, Awad R, Chesson B, Eade T, Wong W, Sasso G, De Abreu Lourenco R, Kron T, Ball D, Neeson P, Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung (SAFRON) II Study Investigators.
- Issue date: 2021 Oct 1
- Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy--a systematic review of randomised trials.
- Authors: Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD
- Issue date: 2003 Sep
- Survival analysis of malignant epidural spinal cord compression after palliative radiotherapy using Tokuhashi scoring system and the impact of systemic therapy.
- Authors: Mui WH, Lam TC, Wong FCS, Sze WK
- Issue date: 2017 Dec
- Metastatic spinal cord compression: radiotherapy outcome and dose fractionation.
- Authors: Hoskin PJ, Grover A, Bhana R
- Issue date: 2003 Aug