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.

Neoadjuvant Arterial Embolization of Spine Metastases Associated With Improved Local Control in Patients Receiving Surgical Decompression and Stereotactic Body Radiotherapy.

BACKGROUND: Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control. OBJECTIVE: To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT). METHOD: A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level. RESULTS: Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort ( P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization ( P < .001). CONCLUSION: Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.

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.

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.

Recurrent adamantinoma metastatic to the spine: Clinical and imaging considerations.

Metastatic adamantinoma involving the spine is an extremely rare occurrence. In this case report, we present a patient with recurrent adamantinoma of the tibia which was found to have metastasized to the spine. The metastatic involvement was diagnosed pathologically, status post CT guided percutaneous core needle biopsy, performed after the patient returned with concerning symptoms and imaging findings suggestive of metastasis. The patient was ultimately treated surgically with vertebrectomy and reconstruction. A thoughtful review of this disease process is explored, emphasizing the pathology, imaging characteristics, and pertinent differential diagnostic considerations. While uncommon, knowledge of this rare disease process and its presentation can improve future patient diagnosis and outcomes.

Endovascular repair and open repair surgery of thoraco-abdominal aortic aneurysms cause drastically different types of spinal cord injury.

Both endovascular repair (EVR) and open repair (OR) surgery of thoraco-abdominal aortic aneurysms cause spinal cord (SC) injury that can lead to paraparesis or paraplegia. It has been assumed that mechanisms responsible for SC damage after EVR are similar to those after OR. This pilot study compared the pathophysiology of SC injury after EVR versus OR using a newly developed EVR dog model. An increasing number of stents similar to those used in patients were inserted in the aorta of three dogs to ensure thoracic or thoracic plus lumbar coverage. The aorta of OR dogs was cross-clamped for 45 min. Behavior assessment demonstrated unique patterns of proprioceptive ataxia and evolving paraparesis in EVR versus irreversible paraplegia in OR. MRI showed posterior signal in lumbar SC after EVR versus central cord edema after OR. Histopathology showed white matter edema in L3-L5 localized to the dorsal column medial lemniscus area associated with loss of myelin basic protein but not neurons after EVR, versus massive neuronal loss in the gray matter in L3-L5 after OR. Metabolome analysis demonstrates a distinctive chemical fingerprint of cellular processes in both interventions. Our results call for the development of new therapeutics tailored to these distinct pathophysiologic findings.

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.

Floating Vertebral Body Cement Ball After High-Viscosity-Cement Vertebroplasty for Lytic Defect: Report of 2 Cases.

BACKGROUND: Percutaneous vertebroplasty (PVP) is an effective procedure for painful pathological vertebral fractures. High-viscosity cement is the preferred choice for vertebroplasty given its low risk of extravasation. We describe here 2 cases of high-viscosity cement vertebroplasty in large lytic defects and associated complications. CASE DESCRIPTION: Case 1 describes PVP in an 89-year-old male patient with L1 pathological fracture from prostrate metastasis. Case 2 describes PVP in a 68-year-old male with T7 and T8 vertebral fractures from multiple myeloma. In both cases, high-viscosity cement was used to fill large lytic cavities. This resulted in poor interdigitation of the cement with the trabeculae forming an unstable floating cement ball and dangerous retrieval of the cement trocar needle. The implications of this occurrence have been described. CONCLUSIONS: High-viscosity-cement vertebroplasty in large lytic defects needs to be done with caution. The potential occurrence of poor cement interdigitation and the following complications can be catastrophic, and caution must be used.

Stereotactic CT image guidance and biplanar fluoroscopy for transoral C2 vertebroplasty and direct anterolateral subaxial vertebroplasty: a surgical technique note on access to the axial and subaxial spine.

BACKGROUND: Metastatic cervical spine disease can cause compression fractures, cervical spine instability, and pain. Vertebroplasty can stabilize a fracture, reduce the pain associated with a compression fracture, prevent or stop the progression of a fracture, thus avoiding cervical spine fixation, and decreased mobility. Transoral C2 vertebroplasty is less invasive than open fusion surgery, but it poses its own risk of infection and cement leak in this highly sensitive area. METHODS: The image guidance setup consisted of the Stryker NAV3i navigation system, Stryker CranialMask tracker, and the CranialMap 3.0 software combined with biplanar fluoroscopy. RESULTS: The patient's neck pain has completely resolved immediately after the surgery. There were no complications. CONCLUSION: Quality of life preservation is paramount in the management of metastatic spine disease. Vertebroplasty of osteolytic lesions can both relieve pain and restore stability, thus avoiding permanent stiff cervical collar, halo vest, or upfront occipitocervical fusion. With the increasing availability of surgical navigation systems, its use combined with biplanar fluoroscopy for performing transoral C2 vertebroplasty seems to be an adequate treatment in selected cases for pain relief, stabilization, and maintaining quality of life in the complex cancer population with C2 pathological fractures. The article describes as well vertebroplasty of the subaxial spine through a conventional anterior approach which again seems to be adequate in the treatment of spinal pathological fractures. Graphical abstract.

Dual-Energy CT-Derived Iodine Content and Spectral Attenuation Analysis of Metastatic Versus Nonmetastatic Lymph Nodes in Squamous Cell Carcinoma of the Oropharynx.

The presence of a single nodal metastasis has significant prognostic and treatment implications for patients with head and neck cancer. This study aims to investigate whether dual-energy computed tomography (DECT)-derived iodine content and spectral attenuation curve analysis can improve detection of nodal metastasis in oropharyngeal carcinoma. Eight patients with newly diagnosed oropharyngeal squamous cell carcinoma and pathologically proven nodal metastatic disease (n = 13 metastatic nodes; n = 16 nonmetastatic nodes) who underwent contrast-enhanced DECT of the neck were retrospectively evaluated. DECT-derived iodine content (mg/mL) and monoenergetic attenuation values at 40 keV and 100 keV were obtained via circular regions of interest within metastatic and nonmetastatic cervical lymph nodes. Iodine content was significantly lower in metastatic nodes (0.96 ± 0.28 mg/mL) than in nonmetastatic nodes (1.65 ± 0.38 mg/mL; P = .002). Iodine spectral attenuation slope was significantly lower in metastatic nodes (1.33 ± 0.49 mg/mL) than in nonmetastatic nodes (1.91 ± 0.64 mg/mL; P = .015). A nodal iodine threshold of ≤1.3 mg/mL showed a sensitivity of 84.6% and a specificity of 75.0%, with an area under the curve of 0.839, P < .0001. At a threshold value of ≤1.95 for nodal spectral attenuation slope, an optimized specificity of 92.3% and specificity of 50.0% was achieved, with an area under the curve of 0.68 (P = .049). DECT-derived quantitative iodine data and spectral attenuation curves may improve the diagnostic accuracy of computed tomography for nodal metastasis in patients with squamous cell carcinoma of the oropharynx.

Magnetic resonance elastography to estimate brain stiffness: Measurement reproducibility and its estimate in pseudotumor cerebri patients.

This study determines the reproducibility of magnetic resonance elastography (MRE) derived brain stiffness in normal volunteers and compares it against pseudotumor patients before and after lumbar puncture (LP). MRE was performed on 10 normal volunteers for reproducibility and 14 pseudotumor patients before and after LP. During LP, opening and closing cerebrospinal fluid (CSF) pressures were recorded before and after removal of CSF and correlated to brain stiffness. Stiffness reproducibility was observed (r > 0.78; p < 0.008). Whole brain opening LP stiffness was significantly (p = 0.04) higher than normals, but no significant difference (p = 0.11) in closing LP measurements. No significant correlation was observed between opening and closing pressure and brain stiffness.

Fluoroscopic-Guided Lumbar Spinal Drain Insertion for Thoracic Aortic Aneurysm Surgery.

We retrospectively reviewed the medical records of 11 patients who were referred by anesthesiologists to an interventional neuroradiologist for fluoroscopy-guided lumbar spinal drain insertion for thoracic aortic aneurysm repair between January 2010 and June 2015. Successful drain insertion was achieved in all patients. Three (27.3%) patients developed drain-related complications. Fluoroscopy-guided spinal drain insertion is an alternative to the conventional, nonimage-guided, blind technique used by anesthesiologists when they expect to encounter difficulty with insertion or in cases of failed insertion.

Postoperative cement augmentation after 360-degree fixation for highly unstable vertebral fractures in patients with multiple myeloma: a technical note on delayed trans-instrumentation vertebroplasty.

BACKGROUND: Although surgical fixation is usually not part of the first-line treatment of spinal lesions in patients with multiple myeloma, there are some unique clinical situations (such as the presence of acute onset of neurological deficits) in which spinal decompression and instrumentation may be required. In such scenario, because of the presence of poor bone quality, the strength of the spinal construct is of paramount importance. Although several studies have demonstrated the benefits of cement augmentation in increasing the pullout strength of pedicle screw fixation, the injection of cement during placement of pedicle screws may hamper the possibility of additional circumferential screw fixation. In addition, cement injection into vertebral bodies full of tumor and in the presence of adjacent epidural disease may incur in higher risks of tumor extravasation and worsening of neurological deficits than cement injection after initiation of adjuvant therapies. CASE DESCRIPTION: The advantages of delayed trans-instrumentation vertebroplasty after 360-degree fixation are discussed in this technical note with an illustrative case of a patient with multiple myeloma presenting with cauda equina syndrome after a T12 compression fracture. CONCLUSIONS: In spite of the associated challenges of such an interventional procedure due to the presence of extensive hardware, carrying out delayed trans-instrumentation vertebroplasty after 360-degree circumferential fixations is not only feasible, but in our opinion, may constitute the best strategy to optimize the strength of spinal instrumentation in challenging scenarios involving poor bone quality, such as in patients with multiple myeloma.

Vertebral compression fractures in patients under treatment with denosumab: a contraindication for percutaneous vertebroplasty?

BACKGROUND CONTEXT: Denosumab (XGeva) is a receptor activator of nuclear factor-κB ligand (RANKL)-antibody that was approved by the Food and Drug Administration (FDA) in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors. Although there is a widespread use of such drug in patients under risk of pathological fractures, the compatibility of denosumab therapy with percutaneous vertebroplasty (an interventional procedure commonly used for pain control in such population) has not yet been established. PURPOSE: To present the serial imaging findings and technical report of an attempted percutaneous vertebroplasty in a patient with refractory pain and a lytic pathological vertebral fracture related to small cell lung cancer spinal metastasis and who was actively under medical treatment with denosumab. STUDY DESIGN: Retrospective review and case report. METHODS: The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department of Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June 2013 (a 30-month period). RESULTS: Although the computed tomography scan of the thoracic spine, performed 6 weeks after the initiation of the treatment with denosumab, presented a remarkable remodeling of the previously lytic vertebral lesion (which became markedly sclerotic in appearance), the clinical response in terms of pain improvement was not satisfactory. At the time of the percutaneous vertebroplasty (which was indicated for pain control), after advancing the 11-gauge needle through the pedicle with extreme difficulty, the needle repeatedly deviated laterally and, despite several attempts, it was not possible to penetrate the vertebral body and perform the cement injection. CONCLUSIONS: This is the first report of the technical peculiarities of percutaneous vertebroplasty in patients under medical treatment with denosumab. According to our experience, because of its RANKL-mediated effects on osteoclasts activity, denosumab has been shown to induce a fast and marked sclerotic response on vertebral bodies that may not be accompanied by a satisfactory improvement in pain control (especially in patients with mechanical type of pain) and which may actually prevent the successful performance of percutaneous vertebroplasty. Therefore, it is of paramount importance that future studies evaluating patients with vertebral fractures under treatment with denosumab include long-term pain outcome measures. Additionally, further investigation is warranted to determine the optimal order of treatment and the best timeframe for combining percutaneous vertebroplasty and denosumab therapy in patients presenting with acute vertebral compression fractures and refractory axial pain.

Preoperative direct percutaneous embolization of spinal metastasis from renal cell carcinoma.

Preoperative direct percutaneous embolization has been very rarely used in hypervascular metastatic spinal tumors to decrease blood loss during the surgery. A patient is presented with solitary spinal metastasis due to renal cell carcinoma who underwent a two-stage spondylectomy. Transarterial tumor embolization with polyvinyl alcohol (PVA) particles and liquid coil placement, and percutaneous tumor embolization with PVA particles were used before the first and the second stage, respectively.

Endovascular therapy for subclavian artery rupture in von Recklinghausen disease.

Vascular anomalies are extremely rare in patients with von Recklinghausen disease. This report presents a case of an acute spontaneous subclavian artery rupture in a patient with von Recklinghausen disease. A 44-year-old woman with a history of neurofibromatosis type 1, multiple sclerosis, and aortic valve replacement experienced a ''popping sensation'' in her neck. An emergent angiogram via a right brachial artery approach revealed active extravasation of contrast from the proximal part of the right subclavian artery between the vertebral and axillary arteries. An 8 mm × 5 cm endoprosthesis stent graft was placed across the area of extravasation via the brachial sheath. Completion angiography revealed brisk flow through the stent graft with resolution of the area of extravasation and no residual stenosis. Arterial rupture, aneurysm formation, stenosis, and dissection can be fatal in patients with neurofibromatosis. Further research is needed to determine screening guidelines and management algorithms for this patient population.