title: Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial.
abstract: BACKGROUND
  Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms.
  
  
  METHODS
  149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443.
  
  
  RESULTS
  Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years.
  
  
  CONCLUSIONS
  SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities.
  
  
  BACKGROUND
  National Cancer Institute of the US National Institutes of Health.
authors.affiliation: Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. xswang@mdanderson.org
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Rhines
authors.forename: Almon S
authors.initials: AS
authors.lastname: Shiu
authors.forename: James N
authors.initials: JN
authors.lastname: Yang
authors.forename: Ugur
authors.initials: U
authors.lastname: Selek
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Gning
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Allen
authors.forename: Syed S
authors.initials: SS
authors.lastname: Azeem
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Hadley J
authors.initials: HJ
authors.lastname: Sharp
authors.forename: David C
authors.initials: DC
authors.lastname: Weksberg
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
authors.forename: Eric L
authors.initials: EL
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000532:radiotherapy*; D009369:Neoplasms / Q000473:pathology; D059408:Pain Management; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D013117:Spinal Cord Compression / Q000473:pathology / Q000532:radiotherapy*; D013120:Spinal Cord Neoplasms / Q000532:radiotherapy* / Q000556:secondary