In a study reported in Journal of Clinical Oncology, Arjun Sahgal, MD, of Princess Margaret Cancer Centre in Toronto, and colleagues evaluated the occurrence of vertebral compression fractures in patients undergoing spinal stereotactic body radiotherapy.1 Vertebral compression fractures occurred in 14% of spinal segments treated, and radiation dose/fraction, vertebral compression fractures at baseline, lytic tumors, and spinal deformity were associated with significantly increased risk of this adverse event.
The study included a total of 252 patients with 410 spinal segments treated with stereotactic body radiotherapy, including 68 patients with 89 spinal segments treated at The University of Texas MD Anderson Cancer Center, Houston, 85 patients with 132 spinal segments treated at the Cleveland Clinic, and 99 patients with 189 spinal segments treated at University of Toronto. The primary outcome was the development of vertebral compression fractures, defined as a new fracture or progression of a baseline fracture.
In addition to patient, treatment, and tumor factors, the Spinal Instability Neoplastic Scoring (SINS) system was used to determine predictive value (Table 1).2 Individual SINS criteria consist of location (junctional, mobile, semirigid, and rigid spine), type of pain (mechanical, nonmechanical) vs pain-free, spinal misalignment (kyphosis/scoliosis, translation/subluxation) vs normal alignment, presence of baseline vertebral compression fractures (≥ 50% collapse, < 50% collapse) vs no collapse but > 50% of the vertebral body involved by tumor vs neither, type of lesion (lytic, mixed, sclerotic), and whether tumor involves the posterolateral elements (bilateral, unilateral) or not.
The scoring system classifies patients as stable, potentially unstable (indeterminate), and unstable based on the overall score. Each treated vertebral segment was scored according to the SINS criteria. Additional factors analyzed included histologic type, paraspinal/epidural disease extension, whether any targeted therapy or bisphosphonates had been given within 2 months before stereotactic body radiotherapy, prior radiation to the treated segment, total dose prescribed, number of fractions, and whether the treated segment included other adjacent segments in the target volume (single vs multiple).
Median follow-up was 11.5 months (range, 0.03–113 months). Median and mean overall survival were 16 and 26 months, respectively. A total of 57 vertebral compression fractures were identified (14% of spinal segments), consisting of 27 new fractures (47% of fractures) and 30 fracture progressions. Median time to vertebral compression fracture was 2.46 months (range, 0.03–43.01 months), with 65% occurring within the first 4 months after stereotactic body radiotherapy. The 1- and 2-year cumulative rates of fracture were 12.35% and 13.49%, respectively.
Mean age was 57 years for patients with and without fractures. Of the 57 fractures, 26 each occurred in the thoracic and lumbar spine and 5 occurred in the cervical spine. Paraspinal/epidural disease was present in 38 cases.
Patients were receiving targeted systemic therapy and bisphosphonates in 31 and 14 cases, respectively, and had received prior radiation in 7 cases. There was a single segment target in 43 cases. Radiation dose/fraction was < 8 Gy in 4 cases, 8 to 11 Gy in 13, 12 to 19 Gy in 22, 20 to 23 Gy in 6, and ≥ 24 Gy in 12.
Bone lesion types were lytic in 48 cases, mixed in 6, and blastic in 3. In 47 cases, patients had normal spinal alignment, with kyphosis/scoliosis present in 9 and subluxation/translation present in 1. Vertebral body collapse was present in 30 cases, with ≥ 50% vertebral body involvement in 3 and < 50% in 27; no collapse but > 50% of vertebral body involvement with the tumor was present in 13 cases. SINS classification was stable in 13 cases, indeterminate in 42, and unstable in 2.
Predictors of Fracture
On multivariate analysis, radiation dose/fraction and baseline vertebral compression fracture, presence of a lytic tumor, and spinal deformity (3 of the 6 SINS criteria) were significant predictors of vertebral compression fracture. For baseline vertebral body collapse, compared with no vertebral compression fracture and < 50% vertebral body involvement, hazard ratios were 6.92 (P = .0189) for ≥ 50% vertebral compression fracture, 8.98 (P < .001) for < 50% vertebral compression fracture, and 4.96 (P < .001) for no vertebral compression fracture but > 50% of vertebral body involved.
Compared with radiation dose/fraction ≤ 19 Gy, hazard ratios were 5.25 (P < .001) for ≥ 24 Gy/fraction and 4.91 (P < .001) for 20 to 23 Gy/fraction. Compared with normal spinal alignment, the hazard ratio was 2.99 (P < .001) for kyphosis/scoliosis or subluxation/translation. Compared with mixed and osteoblastic tumors, the hazard ratio was 3.53 (P = .0022) for osteolytic tumors. Paraspinal/epidural disease extension was a significant predictor on univariate but not multivariate analysis.
The investigators concluded:
Caution must be observed when treating with ≥ 20 Gy/fraction, in particular, for patients with lytic tumor, spinal misalignment, and a baseline vertebral compression fracture. Frequent short-term follow-up is required, as nearly two-thirds of all vertebral compression fractures occurred within the first 4 months. We also conclude that SINS may have utility in predicting patients at high risk of [stereotactic body radiotherapy]-induced [vertebral compression fracture]. ■
Disclosure: For full disclosures of all study authors, please visit jco.ascopubs.org.
1. Sahgal A, Atenafu EG, Chao S, et al: Vertebral compression fracture after spine stereotactic body radiotherapy: A multi-institutional analysis with a focus on radiation dose and the Spinal Instability Neoplastic Score. J Clin Oncol 31:3426-3431, 2013.
2. Fourney DR, Frangou EM, Ryken TC, et al: Spinal Instability Neoplastic Score: An analysis of reliability and validity from the Spine Oncology Study Group. J Clin Oncol 29:3072-3077, 2011.
As reviewed in this issue of The ASCO Post, Sahgal et al reported a multi-institutional analysis aimed at clarifying the risk of developing either new or progressive vertebral body compression fractures following high-dose spinal stereotactic body radiation therapy. In the period studied, they...