Radiotherapy for the prophylaxis of heterotopic ossification: A systematic review and meta-analysis of published data

INTRODUCTION: Following surgery, the formation of heterotopic ossification (HTO) can limit mobility and impair quality of life. Radiotherapy has been proven to provide efficacious prophylaxis against HTO, especially in high-risk settings. PURPOSE: The current review aims to determine the factors influencing HTO formation in patients receiving prophylactic radiotherapy. METHODS: A systematic search of the literature was conducted on Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Studies were included if they reported the percentage of sites developing heterotopic ossification after receiving a specified dose of prophylactic radiotherapy. Weighted linear regression analysis was conducted for continuous or categorical predictors. RESULTS: Extracted from 61 articles, a total of 5464 treatment sites were included, spanning 85 separate study arms. Most sites were from the hip (97.7%), from United States patients (55.2%), and had radiation prescribed postoperatively (61.6%) at a dose of 700cGy (61.0%). After adjusting for radiation site, there was no statistically significant relationship between the percentage of sites developing HTO and radiation dose (p=0.1) or whether radiation was administered preoperatively or postoperatively (p=0.1). Sites with previous HTO formation were more likely to develop recurrent HTO than those without previous HTO formation (p=0.04). There was a statistically significant negative relationship between the HTO development and the cohort mean year of treatment (p=0.007). CONCLUSION: Decreases in rates of HTO over time in this patient population may be a function of more efficacious surgical regimens and prophylactic radiotherapy.