Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

Feasibility, safety, and efficacy of circumferential spine stereotactic body radiotherapy.

Background: With advances in systemic therapy translating to improved survival in metastatic malignancies, spine metastases have become an increasingly common source of morbidity. Achieving durable local control (LC) for patients with circumferential epidural disease can be particularly challenging. Circumferential stereotactic body radiotherapy (SBRT) may offer improved LC for circumferential vertebral and/or epidural metastatic spinal disease, but prospective (and retrospective) data are extremely limited. We sought to evaluate the feasibility, toxicity, and cancer control outcomes with this novel approach to circumferential spinal disease. Methods: We retrospectively identified all circumferential SBRT courses delivered between 2013 and 2019 at a tertiary care institution for post-operative or intact spine metastases. Radiotherapy was delivered to 14-27.5 Gy in one to five fractions. Feasibility was assessed by determining the proportion of plans for which ≥95% planning target volume (PTV) was coverable by ≥95% prescription dose. The primary endpoint was 1-year LC. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity were assessed. Detailed dosimetric data were collected. Results: Fifty-eight patients receiving 64 circumferential SBRT courses were identified (median age 61, KPS ≥70, 57% men). With a median follow-up of 15 months, the 12-month local control was 85% (eight events). Five and three recurrences were in the epidural space and bone, respectively. On multivariate analysis, increased PTV and uncontrolled systemic disease were significantly associated with an increased likelihood of LF; ≥95% PTV was covered by ≥95% prescription dose in 94% of the cases. The rate of new or progressive vertebral compression fracture was 8%. There were no myelitis events or any grade 3+ acute or late toxicities. Conclusions: For patients with circumferential disease, circumferential spine SBRT is feasible and may offer excellent LC without significant toxicity. A prospective evaluation of this approach is warranted.

Quantitative dynamic wearable motion-based metric compared to patient-reported outcomes as indicators of functional recovery after lumbar fusion surgery.

BACKGROUND: Low back pain is a debilitating condition with poor patient outcomes despite the use of a wide variety of diagnostic and treatment modalities. A lack of objective metrics to support clinical decision-making may be a reason for these poor outcomes. This study aimed to compare patient recovery following lumbar fusion surgery using an objective motion-based metric (functional performance) and subjective patient-reported outcomes for pain, disability and kinesophobia. METHODS: A prospective observational study was conducted on 121 patients that received a lumbar fusion surgery. A wearable motion system was used to quantify three-dimensional multi-planar lumbar motion and benchmark each patient's lumbar function prior to surgery and post-operatively at follow-up time points for up to 2 years. Patient recovery profiles after surgery were evaluated using the acquired functional motion data and compared to patient-reported outcomes. FINDINGS: Our results found significant improvement after surgery in objective functional performance as well as patient-reported pain, disability, and kinesophobia. However, we found a delayed response in the objective metric, with meaningful improvement occurring only 6 months after fusion surgery. In contrast, we found significant improvement in all subjective scores as early as 6 weeks post-surgery. INTERPRETATION: Objective motion-based metric provides a unique perspective to assessing patient's functional recovery. While it is associated with dimensions of pain, disability and fear avoidance, it is also distinct and assesses a uniquely different dimension of functional health. This information can form the basis for the use of objective metrics to gauge patient recovery after lumbar fusion surgery.

Spine Stereotactic Body Radiotherapy to Three or More Contiguous Vertebral Levels.

Background: With survival improving in many metastatic malignancies, spine metastases have increasingly become a source of significant morbidity; achieving durable local control (LC) is critical. Stereotactic body radiotherapy (SBRT) may offer improved LC and/or symptom palliation. However, due to setup concerns, SBRT is infrequently offered to patients with ≥3 contiguous involved levels. Because data are limited, we sought to evaluate the feasibility, toxicity, and cancer control outcomes of spine SBRT delivered to ≥3 contiguous levels. Methods: We retrospectively identified all SBRT courses delivered between 2013 and 2019 at a tertiary care institution for postoperative or intact spine metastases. Radiotherapy was delivered to 14-35 Gy in 1-5 fractions. Patients were stratified by whether they received SBRT to 1-2 or ≥3 contiguous levels. The primary endpoint was 1-year LC and was compared between groups. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity was assessed. In-depth dosimetric data were collected. Results: Overall, 165 patients with 194 SBRT courses were identified [54% were men, median age was 61 years, 93% had Karnofsky Performance Status (KPS) ≥70, and median follow-up was 15 months]. One hundred thirteen patients (68%) received treatment to 1-2 and 52 to 3-7 (32%) levels. The 1-year LC was 88% (89% for 1-2 levels vs. 84% for ≥3 levels, p = 0.747). On multivariate analysis, uncontrolled systemic disease was associated with inferior LC for patients with ≥3 treated levels. No other demographic, disease, treatment, or dosimetric variables achieved significance. Rates of new/progressive fracture were equivalent (8% vs. 9.5%, p = 0.839). There were no radiation-induced myelopathy or grade 3+ acute or late toxicities in either group. Coverage of ≥95% of the planning target volume with ≥95% prescription dose was similar between groups (96% 1-2 levels vs. 89% ≥3 levels, p = 0.078). Conclusions: For patients with ≥3 contiguous involved levels, spine SBRT is feasible and may offer excellent LC without significant toxicity. Prospective evaluation is warranted.

Toward an artificial intelligence-assisted framework for reconstructing the digital twin of vertebra and predicting its fracture response.

This article presents an effort toward building an artificial intelligence (AI) assisted framework, coined ReconGAN, for creating a realistic digital twin of the human vertebra and predicting the risk of vertebral fracture (VF). ReconGAN consists of a deep convolutional generative adversarial network (DCGAN), image-processing steps, and finite element (FE) based shape optimization to reconstruct the vertebra model. This DCGAN model is trained using a set of quantitative micro-computed tomography (micro-QCT) images of the trabecular bone obtained from cadaveric samples. The quality of synthetic trabecular models generated using DCGAN are verified by comparing a set of its statistical microstructural descriptors with those of the imaging data. The synthesized trabecular microstructure is then infused into the vertebra cortical shell extracted from the patient's diagnostic CT scans using an FE-based shape optimization approach to achieve a smooth transition between trabecular to cortical regions. The final geometrical model of the vertebra is converted into a high-fidelity FE model to simulate the VF response using a continuum damage model under compression and flexion loading conditions. A feasibility study is presented to demonstrate the applicability of digital twins generated using this AI-assisted framework to predict the risk of VF in a cancer patient with spinal metastasis.

A digital twin for simulating the vertebroplasty procedure and its impact on mechanical stability of vertebra in cancer patients.

We present the application of ReconGAN, introduced in a previous study, for simulating the vertebroplasty (VP) operation and its impact on the fracture response of a vertebral body. ReconGAN consists of a Deep Convolutional Generative Adversarial Network (DCGAN) and a finite element based shape optimization algorithm to virtually reconstruct the trabecular bone microstructure. The VP procedure involves injecting shear-thinning liquid bone cement through a needle in the trabecular region to reinforce a diseased or fractured vertebra. To simulate this treatment modality, computational fluid dynamics (CFD) is employed to predict the morphology of the injected cement within the bone microstructure. A power-law equation is utilized to characterize the non-Newtonian shear-thinning behavior of the polymethyl methacrylate (PMMA) bone cement during injection simulations. The CFD model is coupled with the level-set method to simulate the motion of the interface separating bone cement and bone marrow. After predicting the cement morphology, a data co-registration algorithm is employed to transform the CFD model to a high-fidelity continuum damage mechanics (CDM) finite element model of the augmented vertebra for predicting the fracture response. A feasibility study is presented to demonstrate the ability of this CFD-CDM framework to investigate the effect of VP on the mechanical integrity of the vertebral body in a cancer patient with a lytic metastatic tumor.

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

BACKGROUND: Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. OBJECTIVE: To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. METHODS: We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. RESULTS: A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94% vs 75%, respectively, at 1 yr (P = .03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88% vs 76% for those who did not receive preoperative embolization (P = .037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. CONCLUSION: Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

Assessment of a rabbit posterolateral spinal fusion using movement between vertebrae: a modification of the palpation exam for quantifying fusions.

BACKGROUND: Manual palpation of rabbit spine levels has been used to assess fusion status. This method of testing is subject to inter-observer differences in assessment. We attempted to quantify fusion based on the amount of movement between rabbit vertebrae at the level of fusion. METHODS: Rabbits were divided into three groups. The first underwent a sham surgery; the second underwent a unilateral spinal fusion; and the third underwent a bilateral spinal fusion. All groups were sacrificed at either 5- or 10-week post-procedure. Each spine was tested for fusion using standard manual palpation techniques. The spines were also placed on a specially designed apparatus and moved through 10°, 20°, and 30° of extension/flexion. RESULTS: Out of 10 rabbits, 2 underwent sham surgery, 2 underwent a fusion procedure at L4-L5 and 6 underwent a fusion at L5-L6. We only included rabbits that underwent a L5-L6 fusion surgery. Our apparatus did not always rotate the spine the intended amount with up to 30% error. When rabbits graded as fused were compared to sham rabbits, there was a trend towards reduction in percent of overall measured angle within the fused group as compared to the sham group (8.77% vs. 13.84%, P=0.14). CONCLUSIONS: Our model attempted to quantify the amount of displacement between vertebrae during the manual palpation exam. There is a trend towards reduced measured angle between vertebrae between fused and non-fused spines and no statistically significant difference in overall measured angle between unilaterally and bilaterally fused spines.

The biochemical response to biomechanical tissue loading on the low back during physical work exposure.

BACKGROUND: Our understanding of low back disorder causality is limited in that how biomechanical loading acting on various spinal tissues initiates the pain pathway is not clear. Previous studies suggest that cytokines may be important in mediating the inflammatory responses in patients with back pain. This study quantified the acute biochemical responses to physical work stressing the low back and assessed the relationships between these systemic responses and specific lumbar spine tissue loads. METHODS: Twelve healthy males were tested under control and two weight-lifting conditions (light and heavy). Venous blood was sampled at various time points before and after the physical work and analyzed for cytokine, granulocyte, and creatine kinase levels. Biomechanical data were collected during the tasks and a biologically-assisted lumbar spine model was used to calculate spinal loads at various lumbar spine levels and trunk muscle forces. FINDINGS: Levels of interleukin-6, granulocytes, and creatine kinase all increased after both weight-lifting tasks, with the greatest changes observed with the heavier lifting task. Similarly, plasma levels of interleukin-1ß and tumor necrosis factor-α both increased following the heavier lifting task. These inflammatory responses were significantly correlated with specific spinal tissue loads. INTERPRETATION: This study suggests that it may be possible to use inflammatory cytokines as biomarkers to monitor the physiological responses of the human body to biomechanical loading. Identifying the possible sources of cytokine up-regulation using an advanced biomechanical model may help a more effective understanding of the causal pathways that lead to low back disorders.