Stereotactic Body Radiotherapy of Painful Osseous Metastases: A Correlation Meta-Analysis

Abstract

Osseous metastases are a common cause of cancer pain, only partially palliated by analgesics or conventional radiotherapy (CRT). Stereotactic body radiotherapy (SBRT) is increasingly utilized because of high rates of local disease control reported in large retrospective series. Whether local disease control translates to adequate pain control remains ineffectively evaluated. A recent (as yet unpublished) randomized trial (RTOG 0631) of SBRT vs. CRT for spinal metastases showed no difference in pain control, but several questions about the trial have been raised. Moreover, the proportion of patients experiencing pain relief has been described in several reports, yet the durability of pain relief has not been well-described. In this meta-analysis we sought to analyze the effectiveness and durability of SBRT for pain relief for both appendicular and axial metastases. A systematic review of the English literature was performed for all studies reporting palliative outcomes of SBRT with five or fewer fractions for osseous metastases; studies reporting local control but not pain control were excluded. A random effects model was used to determine the net Pearson product-moment correlation (R2) for post-SBRT pain relief over time. The pooled correlation coefficient and 95% confidence interval were calculated using Fisher r-to-z transformation. Risk of bias was assessed using sunset plots; heterogeneity was assessed using I2 and meta-regression. 449 abstracts were reviewed, 7 full-text articles were included totaling 1100 patients. All studies were prospective in design. All included studies collected data on pain related to osseous metastatic disease pre- and post-SBRT; mean total dose (Gy) and fractions were 17.3 and 2.6 respectively. 4 studies used the brief pain inventory (BPI), 2 used the visual analog scale (VAS) and 1 used QLQ-15. Median follow-up was 24 weeks with a median reduction in pre-radiotherapy pain of 59% (R2 = 0.83, 95%CI:0.80-0.87, I2 = 58.63%). Meta-regression analysis by number of fractions fully accounted for heterogeneity. Sunset plots did not indicate significant publication bias. The published literature is predominately non-randomized with only 1100 patients reported, limiting the evidence level. Pain reduction averages 59% over a median follow-up of 24 weeks. Heterogeneity from palliative therapies prior to SBRT therapy may obscure the full effect of SBRT. SBRT for painful, osseous metastases is associated with pain relief in a majority of patients, but the durability of this relief continues to be inadequately reported in the literature.