Use of Anti-Resorptive Medications prior to Stereotactic Body Radiotherapy for Spinal Metastasis Reduced the Incidence of Vertebral Body Compression Fracture

Abstract

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is frequently utilized for pain relief and tumor control in patients with spinal metastases. A common adverse effect of SBRT is vertebral body compression fracture (VCF), which can be associated with pain and disability. Anti-resorptive (AR) drugs are often given to patients with bone metastases to minimize this risk, but minimal data exist regarding optimal regimens. This study examines the association between peri-SBRT AR drug use and VCF incidence. We hypothesized that patients taking AR drugs prior to SBRT will have lower VCF incidence than those taking them afterward. <h3>Materials/Methods</h3> Patients treated with SBRT for spinal metastases at a single institution from 2009-2020 were retroactively reviewed. Those with primary site multiple myeloma, hemangioma or radiation-level vertebral hardware were excluded. Statistical analysis was performed and p<0.05 was considered significant. Kaplan-Meier survival analysis was used to compare the cumulative incidence of VCF for subgroups including no AR drugs, AR drugs after SBRT only, and AR drugs before SBRT. Cox proportional hazards and Fine-Gray competing risk models were used to separately analyze those taking bisphosphonates (BPs) and those taking denosumab. Model covariates included AR duration, AR cumulative dose, radiation dose and fractionation, BMI, radiotherapy (RT) naivety and total SINS score. Fine-Gray model competing risks were local progression and death. <h3>Results</h3> Of the 234 patients (410 vertebrae) analyzed, 366 (89%) were RT naive. 79 (19.3%) patients were taking BPs alone, 79 (19.3%) were taking denosumab alone, and 49 (12.0%) were taking both. For those taking pre-SBRT AR drugs, the median interval between the last dose of BPs or denosumab and SBRT was 378.3 and 396.3 days. Kaplan-Meier analysis revealed a lower VCF incidence for patients initiating AR drugs before SBRT compared to no AR drugs (6-month 4% vs. 8%, 1-year 4% vs. 12%, 2-year 4% vs 23%, p=0.008). In multivariable analysis, those initiating denosumab prior to SBRT were 81% less likely to develop VCF versus after SBRT (SHR: 0.19, 95% CI [0.04-0.98], p=0.047). There was a trend towards reduced risk of VCF in those initiating BPs prior to SBRT versus after SBRT (SHR: 0.27 [0.06-1.36], p=0.114). Denosumab duration (SHR: 0.99 [0.99-1.01], p=0.45) and cumulative dose (SHR: 1.00 [0.99-1.00], p=0.69) did not affect VCF incidence. BP duration (SHR: 1.14 [1.05-1.24], p=0.003) and cumulative dose (SHR: 0.99 [0.98-0.99], p=0.02) had small statistically significant effects. <h3>Conclusion</h3> These data suggest that denosumab use prior to SBRT may reduce the risk of treatment-induced VCF. AR drugs are underutilized in patients with spine metastases and may represent a useful intervention to improve long-term outcomes. Confirmation of these findings using multi-institution datasets and prospective trials will be important.