Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose–Response for Late Toxicity

Purpose To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. Methods and Materials A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. Results Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED 3 ) > 200 Gy (or EQD2 2Gy [2-Gy equivalent dose calculated using an α/β ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity ( P  = .036). Maximum point BED 3 > 110 Gy (or EQD2 2Gy  > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy ( P  = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. Conclusion Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED 3 > 200 Gy and spinal cord or cauda equina point BED 3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.