Abstract
Objectives: Prospective randomized trials comparing different radiotherapy approaches to guide clinical practice for spinal metastases are lacking. As such, we aimed to perform a systematic review and meta-analysis for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single fraction (SF-SRS) or multiple fraction (MF-SRS)) or conventional radiotherapy (RT) and compare outcomes with different fractionation schedules.
Methods: Thirty-four studies were identified via a PICOS/PRISMA/MOOSE selection protocol including patients with spinal metastases treated with SF-SRS, MF-SRS, or RT with information on dose and fractionation. The primary outcomes were 1-year local control (LC) and acute and late Grade 3-5 toxicities (including vertebral compression fracture (VCF) rates) per the Common Terminology Criteria for Adverse Events (CTCAE) or Radiation Therapy Oncology Group (RTOG), and a secondary outcome of 1-year overall survival (OS). Weighted random effects meta-analyses were conducted using the DerSimonian and Laird methods to characterize summary effect sizes for the primary and secondary outcome measures.
Results: A total of 3,237 patients with 4,911 lesions were analyzed; 2,152 lesions (43.8%) received SF-SRS, 969 lesions (19.7%) received MF-SRS, and 1,790 lesions (36.5%) received RT. Patients treated with SF-SRS had significantly higher 1-year LC (92.9% (95% CI: 86.4-97.4%); p =0.007) as compared to RT (81.0% (95% CI: 69.2-90.5%)) with no difference between MF-SRS (82.1% (95% CI: 76.9-86.8%); p =0.86) or RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4-99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4-93.5%); p=0.007), though again with no difference noted between MF-SRS (82.7% (95% CI: 68.3-93.4%); p=0.88) and RT. On examination of dose-response for SRS, a 4.7% increase in LC was noted for each 10 Gy increase in BED10 (p < 0.001). There was no difference in toxicity rates between SF-SRS (0.4%), MF-SRS (0.2%), or RT (0%). No significant dose-response was identified with regards to VCF rates. One-year OS estimates were 57.2%, 67%, and 32.3% for SF-SRS, MF-SRS, and RT, respectively.
Conclusions: SRS was well-tolerated with minimal severe toxicities. SF-SRS resulted in superior LC for spinal metastases as compared to RT. A significant dose response was found suggesting a roughly 5% increase in LC for every 10 Gy increase in BED10 without a subsequent increase in VCF rates.