Jorrit Jan Verlaan

The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.

Study Design. Systematic literature review. Objective. To address the following questions in a systematic literature review:  1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)?  2. How has SINS affected daily clinical practice?  3. Can SINS be used as a prognostic tool? Summary of Background Data. Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. Methods. PubMed, Embase, and clinical trial databases were searched with the key words “spinal neoplasm,” “spinal instability,” “spinal instability neoplastic score,” and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. Results. The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. Conclusion. No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial. Level of Evidence: N/A

Characteristics of Patients Who Survived 2 Years After Surgery for Spinal Metastases: Can We Avoid Inappropriate Patient Selection?

PURPOSE Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is < 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. PATIENTS AND METHODS A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. RESULTS In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. CONCLUSION Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival.

An Evidence-Based Review and Survey of Expert Opinion of Reconstruction of Metastatic Spine Tumors

Study Design. Systematic review and consensus expert opinion. Objective. To provide surgeons and other health care professionals with guidelines for surgical reconstruction of metastatic spine disease based on evidence and expert opinion. Summary of Background Data. The surgical treatment of spinal metastases is controversial. Specifically two aspects of surgical reconstruction are addressed in this study: (i) choice of bone graft used during surgery for metastatic spine tumors and (ii) the design of reconstruction or construct to stabilize. Methods. A systematic review of the available medical literature from 1980 to 2015 was conducted, and combined with consensus expert opinion from a recent survey of spine surgeons who treat metastatic spine tumors. Results. There is very little evidence in the literature to provide guidance on the use of bone graft in metastatic tumor reconstruction. There is little evidence in the literature to support the preferential use of one graft type over the other. Approximately, 41% of respondents said they used bone graft or bone graft substitutes to accomplish fusion. There were 17 studies that described the use of a prefabricated prosthetic, 10 studies describing the use of polymethyl methacrylate (PMMA) bone cement, and only three studies describing the use of bone graft for anterior column reconstruction. The use of structural allograft was most popular among the experts for anterior reconstruction, followed by cage reconstruction, and PMMA bone cement. Conclusion. Achieving bony union may be of importance for the maintenance of spinal stability in the long term after reconstruction. Whether bony union is required for patients with shorter life expectancies is debatable. The literature supports the use of anterior reconstruction with either a prefabricated prosthetic or PMMA bone cement. It also supports the use of an anterior construct reinforced with bilateral posterior instrumentation when performing a three-column reconstruction. Level of Evidence: N/A

Molecular Markers and Targeted Therapeutics in Metastatic Tumors of the Spine: Changing the Treatment Paradigms.

Study Type. A review of the literature. Objective. The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. Summary of Background Data. Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column. Methods. A review of the literature was performed focusing on illustrative examples of the role that molecular-based therapeutics have played in clinical outcomes for patients diagnosed with metastatic tumor types affecting the spinal column. Results. The impact of molecular therapeutics including receptor tyrosine kinases and immune checkpoint inhibitors and the ability of molecular signatures to provide prognostic information are discussed in metastatic breast cancer, lung cancer, prostate cancer, melanoma, and renal cell cancer affecting the spinal column. Conclusion. For the providers who will ultimately counsel patients diagnosed with metastases to the spinal column, molecular advancements will radically alter the management/surgical paradigms utilized. Ultimately, the translation of these molecular advancements into routine clinical care will greatly improve the quality and quantity of life for patients diagnosed with spinal malignancies and provide better overall outcomes and counseling for treating physicians. Level of Evidence: N/A

Surgeon Reported Outcome Measure for Spine Trauma: An International Expert Survey Identifying Parameters Relevant for the Outcome of Subaxial Cervical Spine Injuries

Study Design. International web-based survey. Objective. To identify clinical and radiological parameters that spine surgeons consider most relevant when evaluating clinical and functional outcomes of subaxial cervical spine trauma patients. Summary of Background Data. Although an outcome instrument that reflects the patients’ perspective is imperative, there is also a need for a surgeon reported outcome measure to reflect the clinicians’ perspective adequately. Methods. A cross-sectional online survey was conducted among a selected number of spine surgeons from all five AOSpine International world regions. They were asked to indicate the relevance of a compilation of 21 parameters, both for the short term (3 mo–2 yr) and long term (≥2 yr), on a five-point scale. The responses were analyzed using descriptive statistics, frequency analysis, and Kruskal-Wallis test. Results. Of the 279 AOSpine International and International Spinal Cord Society members who received the survey, 108 (38.7%) participated in the study. Ten parameters were identified as relevant both for short term and long term by at least 70% of the participants. Neurological status, implant failure within 3 months, and patient satisfaction were most relevant. Bony fusion was the only parameter for the long term, whereas five parameters were identified for the short term. The remaining six parameters were not deemed relevant. Minor differences were observed when analyzing the responses according to each world region, or spine surgeons’ degree of experience. Conclusion. The perspective of an international sample of highly experienced spine surgeons was explored on the most relevant parameters to evaluate and predict outcomes of subaxial cervical spine trauma patients. These results form the basis for the development of a disease-specific surgeon reported outcome measure, which will be a helpful tool in research and clinical practice. Level of Evidence: 4

Clinical and radiological results 6 years after treatment of traumatic thoracolumbar burst fractures with pedicle screw instrumentation and balloon assisted endplate reduction.

BACKGROUND CONTEXT When used to fixate traumatic thoracolumbar burst fractures, pedicle screw constructs may fail in the presence of severe vertebral body comminution as the intervertebral disc can creep through the fractured endplates leading to insufficient anterior column support. Balloon-assisted endplate reduction (BAER) and subsequent calcium phosphate cement augmentation may prevent this event by restoring the disc space boundaries. The results of the first studies using BAER after pedicle screw fixation are encouraging, showing good fracture reduction, few complications, and minimal loss of correction at 2 years of follow-up. PURPOSE To present the clinical and radiological outcome of 20 patients treated for traumatic thoracolumbar burst fractures with pedicle screws and BAER after a minimum of 6 years follow-up. STUDY DESIGN Prospective trial. PATIENT SAMPLE Twenty consecutive neurologically intact adult patients with traumatic thoracolumbar burst fractures were included. OUTCOME MEASURES Radiological parameters (wedge/Cobb angle on plain radiographs and mid-sagittal anterior/central vertebral body height on magnetic resonance imaging scans) and patient reported parameters (EQ-5D and Oswestry Disability Index) were used. METHODS All patients had previously undergone pedicle screw fixation and BAER with calcium phosphate cement augmentation. The posterior instrumentation was removed approximately 1.5 years after index surgery. Radiographs were obtained preoperatively, postoperatively, after removal of the pedicle screws, and at final follow-up (minimum 6 years post-trauma). Magnetic resonance imaging scans were obtained preoperatively, 1 month after index surgery, and 1 month after pedicle screw removal. Health questionnaires were filled out during the last outpatient visit. RESULTS The pedicle screw instrumentation was removed uneventfully in all patients and posterolateral fusion was observed in every case. The mean wedge and Cobb angle converged to almost identical values (5.3° and 5.8°, respectively) and the mid-sagittal anterior and central endplates were reduced to approximately 90% and 80% of the estimated preinjury vertebral body height, respectively; this reduction was sustained at follow-up. Patient-reported outcomes showed favorable results in 79% of the patients. One patient required (posterior) reoperation due to adjacent osteoporotic vertebral body collapse after pedicle screw removal. CONCLUSIONS Balloon-assisted endplate reduction is a safe and low-demanding adjunct to pedicle screw fixation for the treatment of traumatic thoracolumbar burst fractures. It may help achieve minimal residual deformity and reduce the number of secondary (anterior) procedures. Despite these positive findings, one in five patients experienced daily discomfort and disability.

Metastatic Spinal Cord Compression and Steroid Treatment

Study Design: Systematic review. Objectives: We conducted a systematic review of the literature to answer the following questions regarding the use of steroid therapy in metastatic spinal cord compression (MSCC): 1. In cases of MSCC, what is the effect of steroid administration before definitive radiotherapy or surgery on ambulatory status, bowel and bladder function and survival? 2. What steroid dosing regimens are associated with the best outcomes concerning neurological symptoms and complication prevention in cases of MSCC? Summary of Background Data: Currently, there is significant variation in the initial bolus dose, daily maintenance dose and duration of treatment when steroids are used as a bridge to definitive therapy for MSCC. Methods: A literature search following PRISMA guidelines was conducted in June 2016, using Medline via Ovid SP, Medline via PubMed, Embase, Biosis Previews and the Cochrane Library. Search terms used in each database varied slightly to optimize results. All generic steroid formulations were included along with spinal cord compression or myelopathy combined with metastatic or malignant tumors. Papers discussing acute traumatic causes of spinal cord compression were excluded, as were papers discussing cord compression from nonmetastatic tumors or epidural lipomatosis. Subjects were limited to adult humans undergoing definitive treatment with radiotherapy or surgery. Results: Of the 309 papers retrieved, 66 full text studies were reviewed and 6 papers were found to address the stated questions. Conclusions: There is a paucity of high quality literature evaluating the use of steroids in MSCC. On the basis of the evidence available an initial 10 mg intravenous bolus of dexamethasone followed by 16 mg PO QD has been associated with fewer complications compared with 100 mg bolus and 96 mg QD. Weaning of steroids should occur rapidly after definitive treatment. Risk of gastric bleeding or perforation can be managed with the routine use of proton-pump inhibitors. Level of Evidence: Level IIIa.

Superior target delineation for stereotactic body radiotherapy of bone metastases from renal cell carcinoma on MRI compared to CT

BACKGROUND In metastatic renal cell carcinoma (mRCC) there has been a treatment shift towards targeted therapy, which has resulted in improved overall survival. Therefore, there is a need for better local control of the tumor and its metastases. Image-guided stereotactic body radiotherapy (SBRT) in bone metastases provides improved symptom palliation and local control. With the use of SBRT there is a need for accurate target delineation. The hypothesis is that MRI allows for better visualization of the extend of bone metastases in mRCC and will optimize the accuracy of tumor delineation for stereotactic radiotherapy purposes, compared with CT only. METHODS From 2013 to 2016, patients who underwent SBRT for RCC bone metastases were included. A planning CT and MRI were performed in radiotherapy treatment position. Gross tumor volumes (GTV) in both CT and MRI were delineated. Contouring was performed by a radiation oncologist specialized in bone metastases and verified by a radiologist, based on local consensus contouring guidelines. In both CT and MRI, the GTV volumes, conformity index (CI) and distance between the centers of mass (dCOM) were compared. RESULTS Nine patients with 11 RCC bone metastases were included. The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT. The median GTV volume on MRI was 33.4 mL (range 0.2-247.6 mL), compared to 18.1 mL on CT (range 0.1-195.9) (P=0.013). CONCLUSIONS Contouring of RCC bone metastases on MRI resulted in clinically relevant and statistically significant larger lesions (mean increase 41%) compared with CT. MRI seems to represent the extend of the GTV in RCC bone metastases more accurately. Contouring based on CT-only could result in an underestimation of the actual tumor volume, which may cause underdosage of the GTV in SBRT treatment plans.

Loss of Local Tumor Control After Index Surgery for Spinal Metastases: A Prospective Cohort Study

BACKGROUND As survival after treatment for symptomatic spinal metastases increases, the incidence of local tumor recurrence also may increase. However, data regarding incidence and timing of recurrence or duration of survival after second surgeries are not readily available and may help to inform clinicians when to perform second surgeries. OBJECTIVE To identify features associated with loss of local control (LLC) at a previously treated or new spinal level. METHODS Clinical and surgical data were collected from a prospective cohort of 1421 patients who had surgery for symptomatic spinal metastases. Patients undergoing repeat spinal surgery for symptomatic LLC at the same or a different level were identified and analyzed. RESULTS In total, 3.0% patients underwent repeat surgery for symptomatic LLC after a median interval of 184 days from the first surgery; median survival was 6.1 months after second surgery. Factors associated with second surgery for LLC were the primary tumor type, number of spinal levels, Tomita staging, Tokuhashi and Karnofsky scores, anterior surgical approach, more aggressive surgical resection, and postoperative radiotherapy. In total, 1.5% patients were admitted for surgery for a different spinal level than the index operation after median 338 days from the first operation. CONCLUSIONS The likelihood for repeat surgery due to LLC cannot be accurately predicted at the time of initial presentation. Factors associated with second surgery for LLC relate to less aggressive tumor biology and better survival. Most patients had a reasonable duration of survival after second surgery.

Bone mineral density changes over time in diffuse idiopathic skeletal hyperostosis of the thoracic spine

Diffuse idiopathic skeletal hyperostosis (DISH) is an increasingly prevalent ankylosing condition. Patients with DISH have an increased risk of spinal fractures, hypothetically the result of biomechanical changes in the spine. The aim of this study was to analyze the occurrence of biomechanical stress shielding in patients with DISH. To do this, bone mineral density (BMD) was measured longitudinally in the vertebral bodies of subjects with and without DISH and in the newly formed bone of subjects with DISH. The presence of DISH was evaluated using Resnick criteria on two chest computed tomography (CT) scans taken at least 2.5 years apart from subjects over 50 years of age. Three groups were identified: pre-DISH (individuals who developed DISH after the first CT scan), definite DISH (individuals who had DISH on both CT scans), and controls (individuals with no DISH). Hounsfield units (HU) were measured in the newly formed bone and in predefined anterior and posterior portions of the involved vertebral bodies. Mean BMD of the newly formed bone increased significantly (mean ΔHU 137.5; p < 0.01) during a mean interval of 5 years in the cranial, middle, and caudally involved vertebral segments of both DISH groups. Mean BMD of the vertebral bodies in the ankylotic segments in the DISH groups did not significantly differ from that of the non-ankylotic vertebral bodies of the same subject. In contrast to our hypothesis, the HU value of the vertebral body decreased more in the control group than in the DISH groups; however, statistical significance was only reached at the cranial level in the anterior part of the vertebral body (p = 0.048). Our data suggest that 1) vertebral BMD is not influenced by the presence of DISH and 2) increased spinal stiffness may play a more important role than vertebral BMD in the increased fracture risk of and the typical fracture patterns observed in individuals with DISH.