Single versus multifraction radiotherapy for spinal cord compression: A systematic review and meta-analysis

Published:February 02, 2019DOI:


      • Single (SFRT) and short course multifraction (MFRT) regimens for spinal cord compression were compared in a systematic review and meta-analysis.
      • There was no observed difference with respect to motor response, bladder dysfunction and OS between SFRT and MFRT for MESCC, based on moderate quality evidence.
      • Firm conclusions cannot be drawn for SFRT versus MFRT in terms of pain control, QOL or toxicity.
      • Future investigations should focus on these outcomes and treatment for patients with a better expected prognosis.



      While multifraction radiotherapy (RT) regimens (MFRT) have been considered the standard of care in patients with metastatic epidural spinal cord compression (MESCC) with limited prognosis, recent randomized evidence has demonstrated that single fraction RT (SFRT) may be equivalent in terms of functional and overall outcomes. A systematic review and meta-analysis was conducted to determine the effects of SFRT compared to short course MFRT in patients with MESCC.


      A search of OVID, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2018 was conducted. Randomized and prospective non-randomized trials comparing SFRT and short course MFRT for MESCC were included. Data were analyzed using a random effects model, and relative risks (RR) or hazard ratios (HR) were reported with corresponding 95% confidence intervals (CI). Quality of evidence was assessed using the GRADE criteria.


      Overall 1717 articles were reviewed. Three randomized trials were eligible for inclusion (n = 712 patients). The pooled treatment effect for SFRT versus MFRT with respect to motor response was RR = 0.96 (95% CI = 0.86–1.07, I2 = 19%), HR = 1.00 (95% CI = 0.88–1.13, I2 = 0%) for OS, and RR = 0.97, (95% CI = 0.85–1.11, I2 = 61%) for bladder function. There was insufficient data to perform a meta-analysis on quality of life, toxicity or pain response, however available information suggests pain response appears similar between SFRT and MFRT. Overall quality of evidence was deemed moderate due to risk of bias.
      There was no evidence of an observed difference with respect to motor response, bladder dysfunction and OS between SFRT and MFRT for MESCC in patients with a limited prognosis.


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        • Loblaw D.A.
        • Mitera G.
        • Ford M.
        • Laperriere N.J.
        A 2011 updated systematic review and clinical practice guideline for the management of malignant extradural spinal cord compression.
        Int J Radiat Oncol Biol Phys. 2012; 84: 312-317
        • Loblaw D.A.
        • JPerry J.
        • Chambers A.
        • et al.
        Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines initiative‘s neuro-oncology disease site group.
        J Clin Oncol. 2005; 23: 2028-2037
        • Patchell R.
        • Tibbs P.
        • Regine W.
        • et al.
        Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial.
        Lancet. 2005; 366: 643-648
        • Rades D.
        • Segedin B.
        • Conde-Moreno A.
        • et al.
        Radiotherapy with 4 Gy x 5 versus 3Gy x 10 for metastatic epidural spinal cord compression: final results of the SCORE-2 trial (ARO 2009/01).
        JCO. 2016; 34: 597-603
        • Rades D.
        Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression.
        J Clin Oncol. 2005 May 20; 23: 3366-3375
        • Rades D.
        • Panzer A.
        • Rudat V.
        • et al.
        Dose escalation of radiotherapy for Metastatic Spinal Cord Compression (MSCC) in patients with relatively favorable survival prognosis.
        Strahlenther Onkol. 2011; 187: 729-735
        • Qu S.
        • Meng H.L.
        • Liang Z.G.
        • et al.
        Comparison of short course radiotherapy versus long-course radiotherapy for treatment of metastatic spinal cord compression: a systematic review and meta-analysis.
        Medicine (Baltimore). 2015; 94 (Published online 2015 Oct 30)
        • Rades D.
        • Huttenlocher S.
        • Šegedin B.
        • et al.
        Single-fraction versus 5-fraction radiation therapy for metastatic epidural spinal cord compression in patients with limited survival prognoses: results of a matched-pair analysis.
        Int J Radiat Oncol Biol Phys. 2015; 93: 368-372
        • Maranzano E.
        • Trippa F.
        • Casale M.
        • et al.
        8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial.
        Radiother Oncol. 2009; 93: 174-179
        • Thirion P.
        • O’Sullivan L.
        • Clayton-Lea A.
        • et al.
        ICORG 05-03: prospective randomized non-inferiority phase 3 trial comparing two radiation schedules in malignant spinal cord compression not proceeding with surgical decompression.
        Int J Radiat Oncol Biol Phys. 2014; 90: 1263-1264
        • Lee K.
        • Dunne M.
        • Small C.
        • et al.
        (ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis.
        Acta Oncol. 2018;
        • Hoskin P.
        • Misra V.
        • Hopkins K.
        • et al.
        SCORAD III: Randomized non-inferiority phase III trial of single-dose radiotherapy (RT) compared to multi-fraction RT in patients with metastatic spinal cord compression (SCC).
        JCO. 2017; 35 (published online before print)
        • Rades D.
        • et al.
        Validation of a score predicting post-treatment ambulatory status after radiotherapy for metastatic spinal cord compression.
        Int J Radiat Oncol Biol Phys. 2011; 79: 1503-1506
        • Rades D.
        • et al.
        Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression.
        Cancer. 2010; 116: 3670-3673
      1. Higgins J.P.T. Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 (Available from)
      2. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.3. US Department of Health, National Institutes of Health and National Cancer Institute. 2010. Published online:

        • Bilsky M.
        • Laufer I.
        • Fourney D.
        • et al.
        Reliability analysis of epidural spinal cord compression scale.
        J Neurosurg spine. 2010; 13: 324-328
      3. Review Manager (RevMan), [Computer program]. Version 5.3 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014

      4. GetData Graph Digitizer software. Cologne, Germany. (2018). Downloaded from: April 18 2018.

        • Tierney J.F.
        • Stewart L.A.
        • Ghersi D.
        • et al.
        Practical methods for incorporating summary time-to-event data in a meta-analysis.
        Trials. 2007; 7: 8-16
      5. Deeks JJ, Higgins JPT, Altman DG (ed.). Chapter 9: Analysing data and undertaking meta-analyses. Section In: Higgins JPT, Green S (ed.). Cochrane handbook for systematic reviews of interventions version 5.0.2 (updated September 2009). The Cochrane Collaboration, 2009. Available from

      6. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). Available from

        • Giraldo A.
        • Benavente S.
        • Ramos M.
        • et al.
        Effectiveness of radiotherapy for metastatic spinal cord compression in patients with short life expectancy.
        Rep Pract Oncol Radiother. 2017; 22: 58-63
      7. Nguyen J, Chow E, Zeng L et al. Palliative response and functional interference outcomes using the Brief Pain Inventory for spinal bony metastases treated with conventional radiotherapy. Clin Oncol 23(7):485-491.

        • Bone Pain Trial Working Party
        8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.
        Radiother Oncol. 1999; 52: 111-121
        • Zaikova O.
        • Fossa S.
        • Bruland O.S.
        • et al.
        Radiotherapy or surgery for spine metastases?.
        Acta Orthop. 2011; 82: 365-371
        • Rades D.
        • Lange M.
        • Veninga T.
        • et al.
        Final results of a prospective study comparing the local control of short-course and long-course radiotherapy for metastatic spinal cord compression.
        Int J Radiat Oncol Biol Phys. 2011; 79: 524-530
        • Ryu S.
        • Yoon H.
        • Stessin A.
        • et al.
        Contemporary treatment with radiosurgery for spine metastasis and spinal cord compression in 2015.
        Radiat Oncol. 2015; 33: 1-11
        • Klimo P.
        • Thompson C.J.
        • Kestle R.W.
        • et al.
        A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease.
        Neuro-Oncology. 2005; 7: 64-76
        • Raison N.T.J.
        • Alwan W.
        • Abbot A.
        • et al.
        The reliability of red flags in spinal cord compression.
        Acute Trauma. 2014; 3: e78150
        • Cook D.J.
        • Guyatt G.H.
        • Ryan G.
        • et al.
        Should unpublished data be included in meta-analysis? Current convictions and controversies.
        JAMA. 1993; 269: 2749-2753
      8. Tetzlaff J, Moher D, Pham B, et al. Survey of views on including grey literature in systematic reviews. In: Come to the craic. Abstracts of the 14th Cochrane Colloquium; 2006. 23–26 Oct; Dublin, UK. 2006.

        • Bollen L.
        • Jacobs W.C.H.
        • Van der Linden Y.M.
        • et al.
        A systematic review of prognostic factors predicting survival in patients with spinal bone metastasis.
        Eur Spine J. 2018; 27: 799-805
        • Spratt D.E.
        • Beeler W.H.
        • deMoraes F.Y.
        • et al.
        An integrated multidisciplinary algorithm for the management of spinal metastasis: an International Spine Oncology Consortium report.
        Lancet Oncol. 2017; 18: E720-E730
        • Fairchild A.
        • Barnes E.
        • Ghosh S.
        • et al.
        International patterns of practice in palliative radiotherapy for painful bone metastasis: evidence-based practice?.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1501-1510
        • Van der Linden Y.
        • RoosD Lutz S
        • et al.
        International variations in radiotherapy fractionation for bone metastasis: geographic borders define practice patterns?.
        Clin Oncol (R Coll Radiol). 2009; 21: 655-658