Daryl R. Fourney

Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients

Object The current North American experience with minimally invasive vertebro- and kyphoplasty is largely limited to the treatment of benign osteoporotic compression fractures. The objective of this study was to assess the safety and efficacy of these procedures for painful vertebral body (VB) fractures in cancer patients. Methods The authors reviewed a consecutive group of cancer patients (21 with myeloma and 35 with other primary malignancies) undergoing vertebro- and kyphoplasty at their institution. Ninety-seven (65 vertebro- and 32 kyphoplasty) procedures were performed in 56 patients during 58 treatment sessions. The mean patient age was 62 years (+/- 13 years [standard deviation]) and the median duration of symptoms was 3.2 months. All patients suffered intractable spinal pain secondary to VB fractures. Patients noted marked or complete pain relief after 49 procedures (84%), and no change after five procedures (9%); early postoperative Visual Analog Scale (VAS) pain scores were unavailable in four patients (7%). No patient was worse after treatment. Reductions in VAS pain scores remained significant up to 1 year (p = 0.02, Wilcoxon signed-rank test). Analgesic consumption was reduced at 1 month (p = 0.03, Wilcoxon signed-rank test). Median follow-up length was 4.5 months (range 1 day-19.7 months). Asymptomatic cement leakage occurred during vertebroplasty at six (9.2%) of 65 levels; no cement extravasation was seen during kyphoplasty. There were no deaths or complications related to the procedures. The mean percentage of restored VB height by kyphoplasty was 42 +/- 21%. Conclusions Percutaneous vertebro- and kyphoplasty provided significant pain relief in a high percentage of patients, and this appeared durable over time. The absence of cement leakage-related complications may reflect the use of 1) high-viscosity cement; 2) kyphoplasty in selected cases; and 3) relatively small volume injection. Precise indications for these techniques are evolving; however, they are safe and feasible in well-selected patients with refractory spinal pain due to myeloma bone disease or metastases.

A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group.

Study Design. Systematic review and modified Delphi technique. Objective. To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability. Summary of Background Data. Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors. Methods. We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability. Results. A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus. Conclusion. The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.

Spinal Instability Neoplastic Score: An Analysis of Reliability and Validity From the Spine Oncology Study Group

PURPOSE Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS). METHODS Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable. RESULTS The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766). CONCLUSION SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.

Poor drug distribution as a possible explanation for the results of the PRECISE trial

OBJECT Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. METHODS Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. RESULTS Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. CONCLUSIONS The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Spinal cord ependymoma: Radical surgical resection and outcome

OBJECTIVE Several authors have noted increased neurological deficits and worsening dysesthesia in the postoperative period in patients with spinal cord ependymoma. We describe the neurological progression and pain evolution of these patients over the 1-year period after surgery. In addition, our favored method of en bloc tumor resection is illustrated, and the rate of complications, recurrence, and survival in this group of patients is addressed. METHODS We operated on 26 patients (12 male and 14 female) with low-grade spinal cord ependymomas between 1975 and 2001. The median age at diagnosis was 42 years. Tumors extended into the cervical cord in 13 patients, the thoracic cord in 7 patients, and the conus medullaris in 6 patients. Eleven patients had previous surgery and/or radiation therapy. RESULTS We achieved a gross total resection in 88% of patients, whereas 8% had a subtotal resection and 4% had a biopsy. Only 1 patient developed a recurrence over a mean follow-up period of 31 months. CONCLUSION We conclude that radical surgical resection of spinal cord ependymomas can be safely achieved in the majority of patients. A trend toward neurological improvement from a postoperative deficit can be expected between 1 and 3 months after surgery and continues up to 1 year. Postoperative dysesthesias begin to improve within 1 month of surgery and are significantly better by 1 year after surgery. The best predictor of outcome is the preoperative neurological status.

Reliability analysis of the epidural spinal cord compression scale.

OBJECTIVE The evolution of imaging techniques, along with highly effective radiation options has changed the way metastatic epidural tumors are treated. While high-grade epidural spinal cord compression (ESCC) frequently serves as an indication for surgical decompression, no consensus exists in the literature about the precise definition of this term. The advancement of the treatment paradigms in patients with metastatic tumors for the spine requires a clear grading scheme of ESCC. The degree of ESCC often serves as a major determinant in the decision to operate or irradiate. The purpose of this study was to determine the reliability and validity of a 6-point, MR imaging-based grading system for ESCC. METHODS To determine the reliability of the grading scale, a survey was distributed to 7 spine surgeons who participate in the Spine Oncology Study Group. The MR images of 25 cervical or thoracic spinal tumors were distributed consisting of 1 sagittal image and 3 axial images at the identical level including T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images. The survey was administered 3 times at 2-week intervals. The inter- and intrarater reliability was assessed. RESULTS The inter- and intrarater reliability ranged from good to excellent when surgeons were asked to rate the degree of spinal cord compression using T2-weighted axial images. The T2-weighted images were superior indicators of ESCC compared with T1-weighted images with and without Gd. CONCLUSIONS The ESCC scale provides a valid and reliable instrument that may be used to describe the degree of ESCC based on T2-weighted MR images. This scale accounts for recent advances in the treatment of spinal metastases and may be used to provide an ESCC classification scheme for multicenter clinical trial and outcome studies.

Chronic low back pain: A heterogeneous condition with challenges for an evidence-based approach

“Chronic” low back pain (LBP), defined as present for 3 or more months, has become a major socioeconomic problem insufficiently addressed by five major entities largely working in isolation from one another – procedural based specialties, strength based rehabilitation, cognitive behavioral therapy, pain management and manipulative care. As direct and indirect costs continue to rise, many authors have systematically evaluated the body of evidence in an effort to demonstrate the effectiveness (or lack thereof) for various diagnostic and therapeutic interventions. The objective of this Spine Focus issue is not to replicate previous work in this area. Rather, our expert panel has chosen a set of potentially controversial topics for more in-depth study and discussion. A recurring theme is that chronic LBP is a heterogeneous condition, and this affects the way it is diagnosed, classified, treated, and studied. The efficacy of some treatments may be appreciated only through a better understanding of heterogeneity of treatment effects (i.e., identification of clinically relevant subgroups with differing responses to the same treatment). Current clinical guidelines and payer policies for LBP are systematically compared for consistency and quality. Novel approaches for data gathering, such as national spine registries, may offer a preferable approach to gain meaningful data and direct us towards a “results-based medicine.” This approach would require more high-quality studies, more consistent recording for various phenotypes and exploration of studies on genetic epidemiologic undertones to guide us in the emerging era of “results based medicine.”

Safeguards to Prevent Neurologic Complications after Epidural Steroid Injections: Consensus Opinions from a Multidisciplinary Working Group and National Organizations

Background: Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections. Methods: A collaboration was undertaken between the U.S. Food and Drug Administration Safe Use Initiative, an expert multidisciplinary working group, and 13 specialty stakeholder societies. The goal of this collaboration was to review the existing evidence regarding neurologic complications associated with epidural corticosteroid injections and produce consensus procedural clinical considerations aimed at enhancing the safety of these injections. U.S. Food and Drug Administration Safe Use Initiative representatives helped convene and facilitate meetings without actively participating in the deliberations or decision-making process. Results: Seventeen clinical considerations aimed at improving safety were produced by the stakeholder societies. Specific clinical considerations for performing transforaminal and interlaminar injections, including the use of nonparticulate steroid, anatomic considerations, and use of radiographic guidance are given along with the existing scientific evidence for each clinical consideration. Conclusion: Adherence to specific recommended practices when performing epidural corticosteroid injections should lead to a reduction in the incidence of neurologic injuries.

Evaluating the Correlation and Responsiveness of Patient-reported Pain With Function and Quality-of-life Outcomes After Spine Surgery

Study Design. Systematic review. Objective. To determine the correlation of patient-reported pain with physical function and health-related quality of life (HRQoL) after spine surgery and to determine the responsiveness of pain, physical function, and HRQoL after spine surgery. Summary of Background Data. Several validated outcome instruments are available to assess the success of treatment for chronic low back pain. These patient-centered tools include measurements for pain based on numeric scales, validated condition-specific functional outcomes measures, and HRQoL outcomes measures. It is unclear whether these three types of patient-reported outcomes are measuring different constructs and whether all three should be measured after spine surgery. In addition, it is unclear which of these outcomes measures is most sensitive to change after spine surgery for low back pain. Methods. A systematic search was conducted in MEDLINE, EMBASE, and the Cochrane Collaboration Library for literature published through December 2010. The correlation between pain (visual analog scale, VAS), physical function (Oswestry Disability Index, ODI), and HRQoL (36-Item Short Form Health Survey [SF-36] and European Quality of Life [EQ-5D]) change scores was performed using the Spearman rank correlation coefficients. To compare the responsiveness of pain, function, and HRQoL scores after spine surgery, we calculated effect sizes by dividing change scores by the SD of the baseline scores. This standardized method allowed us to compare the responsiveness of each outcome measure directly and reported an effect size of 0.2 to 0.3 as a “small” effect, around 0.5 a “medium” effect and 0.8 to infinity, a “large” effect. To determine whether the differences in effect sizes measuring responsiveness were significantly different, we conducted a Wilcoxon signed-rank test between each of the three measurements of pain, function, and HRQoL scores when there was enough data to perform the test. Results. None of the correlations exceeded 0.70 using the Spearman rank correlation coefficients, suggesting that these outcomes are measuring different constructs. The strongest correlations were between the VAS back pain change scores and the SF-36 physical composite score change scores (&rgr; = 0.67) and VAS back pain change scores and ODI change scores (&rgr; = 0.69). The pooled mean effect sizes for the five studies that reported a pain measure and the ODI were 1.4 ± 0.57 and 1.1 ± 0.39, respectively. Both are considered “large” effect sizes. The pooled mean effect sizes for the three studies reporting the SF-36 physical and mental composite scores were 0.66 ± 0.39 and 0.54 ± 0.36, respectively. Both are considered “medium” effect sizes. The pooled mean effect sizes for the single studies reporting the EQ-5D and SF-36 total score were 0.78 ± 0.12 and 0.34 ± 0.21. These were “medium” and “small,” respectively. Conclusion. We observed little correlation between the change in pain and the change in HRQoL outcomes measures. The strongest correlation was between VAS pain and ODI but was still not considered strong (0.69). These findings suggest that these three outcomes (pain, function, and HRQoL) are measuring different constructs. With respect to responsiveness, VAS pain and ODI were the only outcomes measures that demonstrated a large effect after lumbar spine surgery. None of the HRQoL tools were as sensitive to the treatment. The EQ-5D, SF physical composite, and SF mental composite outcomes demonstrated a medium effect, while the SF-36 total score demonstrated a small effect. The responsive measure shows that the more specific the outcomes tool, the more sensitive the response. Clinical Recommendations. Recommendation 1: When surgically treating CLBP, we recommend administering both a VAS for pain and a condition-specific physical measure such as the ODI before and after surgical intervention as these outcomes are the most treatment specific and responsive to change. Strength of recommendation: Strong. Recommendation 2: When evaluating the surgical outcomes for CLBP in the clinical-research setting, we recommend selecting a shorter version for measuring general HRQoL (e.g., SF-12, EQ-5D) to minimize clinician and patient burden. Strength of recommendation: Strong.

Feasibility and Safety of En Bloc Resection for Primary Spine Tumors: A Systematic Review by the Spine Oncology Study Group

Study Design. Systematic review. Objectives. To determine the general feasibility and safety of en bloc resection for primary spine tumors by analyzing (1) the effect of incisional biopsy performed before definitive en bloc resection and (2) the rate of achievement of disease-free margins, morbidity, mortality, and health resource utilization. Summary of Background Data. The feasibility of en bloc resection is determined by careful surgical and oncologic staging, and a key step in this process is obtaining a tissue diagnosis. There is currently good evidence to support the premise that the best chance for surgical cure in primary tumors of the spine is by en bloc resection with disease-free margins; however, the early morbidity of these procedures begs the question of whether they are justified. Methods. A formal systematic review with search of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews databases was undertaken. Included reports described patients with low grade malignant spine tumors, the method of staging and surgical resection, and the complications. Two blinded, independent reviewers used a standardized study selection worksheet. Results. About 89 articles were identified, with 8 selected after excluding small case series and studies that included other pathologies (e.g., metastatic disease). Weinstein, Boriani, Biagini staging accurately predicted the attainment of wide or marginal en bloc resection in 88% of cases. There was a clear increase in tumor recurrence when intralesional procedures were performed before the definitive en bloc resection. Tumor recurrence significantly shortened patient survival. Surgical complication rates ranged from 13% to 56% and mortality ranged from 0% to 7.7%. Conclusion. (1) Incisional biopsy or intralesional resection significantly increases the risk of local recurrence, therefore, transcutaneous computed tomography-guided trocar biopsy is recommended. When there is a suspicion of primary spine tumor, the surgeon who performs the definitive surgery should ideally perform or direct the biopsy procedure. (2) En bloc resection is achievable if staging determines that it is feasible. The adverse event profile of these surgeries is high even at experienced centers. Therefore, experienced, multidisciplinary teams should perform these surgeries. (3) Grade of Recommendation can be “strong recommendation, low-quality evidence.”