Vertebral body collapse after spine stereotactic body radiation therapy: a single-center institutional experience

About a third of cancer patients will develop bone metastases during the course of their disease.¹ The most common site of bone metastasis is the spine, which can often present with back pain, vertebral body collapse (VBC), radiculopathy, and epidural spinal cord compression.² Compression of the spinal cord has the potential to cause serious harm with symptoms ranging from pain to paralysis.² Optimal management of spine metastases involves multidisciplinary collaboration between surgeons, medical oncologists, pain specialists, and radiation oncology. For patients who are not candidates for immediate neurosurgical intervention, management often involves palliative radiotherapy with the goal of providing symptomatic relief of pain and preventing further progression of disease. With technological advancements in the delivery of radiotherapy, stereotactic body radiation therapy (SBRT) has emerged as an effective technique to safely treat spinal metastases with high doses of radiation while sparing surrounding healthy tissue.³

Delivery of spine SBRT involves precise treatment planning and patient setup utilizing computed topography image verification to ensure the radiation is delivered conformally to the target. The advantages of treating malignant spine metastases with SBRT is controversial. A recent meta-analysis showed the overall pain response may be similar compared to conventional external beam radiotherapy (cEBRT), but more patients had complete pain alleviation with SBRT.⁴ Other studies have shown advantages of SBRT compared to cEBRT such as improved local control and pain relief.^5,6,7 With advances in systemic therapies improving survival for many types of malignancies, local control of all metastatic disease has become increasingly important. Several drawbacks to spine SBRT, however, are increased risks of pain flare and radiation induced VBC. Current literature suggests the rate of VBC is between 4% and 39% for patients with metastatic disease undergoing spine SBRT.^{8,9,10,11,12,13} Chronic pain and kyphotic deformity caused by VBC may lead to depression, impaired mobility, and reduced quality of life.¹⁴ One study also found no clinically relevant differences between conventional radiotherapy and SBRT at 12 weeks for global quality of life, physical functioning, emotional functioning, functional interference, and psychosocial aspects.¹⁵ This necessitates further exploration into the side effects of SBRT.

Multiple risk factors for VBC following spine SBRT have been identified, which include vertebral body involvement, kyphotic/scoliotic spine deformity, lytic tumor, lung and hepatocellular histology, and single-fraction SBRT to a dose of 20 Gy or higher.^9,16 In developing a tool to predict the risk of VBC after spine SBRT, epidural tumor extension, lumbar location, gross tumor volume, and spinal instability neoplastic score (SINS) of more than 6 were associated with increased risk of fracture.¹⁷ While risk factors and predictive models are helpful in identifying patients at high risk of VBC, it remains unclear how to best reduce fracture incidence while also providing effective palliation.

Kyphoplasty is a minimally invasive procedure used in the management of VBC that uses an inflatable balloon to restore bone height then inject bone cement into the vertebral body.¹⁸ This has been shown to be safe and effective for controlling pain in patients with spine metastases.^19,20 Few studies have investigated the effect of prophylactic kyphoplasty prior to spine SBRT on reducing the risk of VBC. The purpose of the present study is to expand on the published experience of spine SBRT and review our single-institution outcomes of spine SBRT with and without prophylactic kyphoplasty as it relates to SINS and VBC.

A total of 83 patients with 100 treated spine segments were included for analysis. There were 10 patients with simultaneously treated synchronous metastases and 7 patients with metachronous metastases. Baseline patient characteristics and treatment details are described in Table 1. The median age was 68 years (interquartile range [IQR], 59−74) and 51% of patients were male. Median follow up time was 12.1 months (IQR, 5.0−25.5). The most common primary tumor histology treated was lung (29%), followed by renal (24%) and prostate (12%). Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. Categories with (n = 100) are lesion-level variables and categories with (n = 83) are patient variables. The 100 lesions were assumed independent events for patients with multiple lesions. SINS for each spine segment prior to SBRT are summarized in Table 2.

Following SBRT there were 10 spine segments that developed VBC (10%), 9 which were de novo VBC and 1 that was progression of a prior VBC. Median time to VBC was 2.4 months (IQR, 0.9−4.0). Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No clinical or SINS factors were associated with VBC upon univariate analysis.

This study reviewed a large single-institutional experience with spine SBRT through evaluation of VBC and SINS. As implementation of spine SBRT into practice continues to evolve, there is greater need for tools to identify patients at highest risk of adverse events such as VBC. We report the risk of VBC to be 10%, which agrees with other studies that found the risk to range from 4% to 39%.^{8,9,10,11,12,13} The wide range of published VBC rates likely owes to differences in treatment technique and patient selection. Unlike previous reports, our study was unable to identify additional clinical or SINS factors associated with VBC. A systematic review of studies examining risk of VBC post-SBRT and reporting risk factors identified lytic disease, baseline VBC prior to SBRT, higher dose per fraction SBRT, spinal deformity, older age, and more than 40% to 50% of vertebral body involved by tumor to be the most frequent factors associated with VBC on Multivariable analysis.²³

Management of a radiation induced VBC can be challenging and may require surgical intervention. In a review of patients developing VBC after spine SBRT, they found that 32% of patients needed a salvage spinal reconstruction procedure, consisting primarily of percutaneous cement augmentation procedures in 77% of patients while the remaining patients required open spinal reconstructive surgery.²⁴ Method of salvage intervention is institutionally dependent and will vary based on resources available, clinical factors, and patient performance status. While spinal instrumentation may provide greater stability than cement augmentation procedures such as kyphoplasty, these are more invasive procedures and typically result in more post-operative pain.

A key finding from our study is no post-treatment VBC occurred in patients that underwent prophylactic kyphoplasty prior to SBRT. While kyphoplasty prior to spine SBRT has previously been shown to be safe and effective in small series, neither reported rates of subsequent VBC.^25,26 In agreement with these findings, another study found the incidence of VBC to be lower in patients that underwent surgical intervention or vertebroplasty prior to SBRT.¹⁷ The optimal timing and patient selection for kyphoplasty in those undergoing spine SBRT still remains under investigation. By utilizing previously identified risk factors, patients at high risk of fracture should be considered for kyphoplasty to protect them from complications prior to ablative therapy with SBRT.

The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.