Survival in Patients With Spinal Metastatic Disease Treated Nonoperatively With Radiotherapy: Are the SORG-ML Algorithms Relevant?

SUMMARY OF BACKGROUND DATA: The SORG-ML algorithms for survival in spinal metastatic disease were developed in patients who underwent surgery and were externally validated for patients managed operatively. OBJECTIVE: To externally validate the SORG-ML algorithms for survival in spinal metastatic disease in patients managed nonoperatively with radiation. STUDY DESIGN: Retrospective cohort. METHODS: The performance of the SORG-ML algorithms was assessed by discrimination [receiver operating curves and area under the receiver operating curve (AUC)], calibration (calibration plots), decision curve analysis, and overall performance (Brier score). The primary outcomes were 90-day and 1-year mortality. RESULTS: Overall, 2074 adult patients underwent radiation for spinal metastatic disease and 29% (n=521) and 59% (n=917) had 90-day and 1-year mortality, respectively. On complete case analysis (n=415), the AUC was 0.76 (95% CI: 0.71-0.80) and 0.78 (95% CI: 0.73-0.83) for 90-day and 1-year mortality with fair calibration and positive net benefit confirmed by the decision curve analysis. With multiple imputation (n=2074), the AUC was 0.85 (95% CI: 0.83-0.87) and 0.87 (95% CI: 0.85-0.89) for 90-day and 1-year mortality with fair calibration and positive net benefit confirmed by the decision curve analysis. CONCLUSION: The SORG-ML algorithms for survival in spinal metastatic disease generalize well to patients managed nonoperatively with radiation.

Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

BACKGROUND: Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. OBJECTIVE: The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. METHODS: Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. RESULTS: Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n = 148, 90%) presented with localized disease, with half (n = 82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n = 10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p < 0.001). CONCLUSION: Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

External validation of a predictive algorithm for in-hospital and 90-day mortality after spinal epidural abscess.

BACKGROUND CONTEXT: Mortality in patients with spinal epidural abscess (SEA) remains high. Accurate prediction of patient-specific prognosis in SEA can improve patient counseling as well as guide management decisions. There are no externally validated studies predicting short-term mortality in patients with SEA. PURPOSE: The purpose of this study was to externally validate the Skeletal Oncology Research Group (SORG) stochastic gradient boosting algorithm for prediction of in-hospital and 90-day postdischarge mortality in SEA. STUDY DESIGN/SETTING: Retrospective, case-control study at a tertiary care academic medical center from 2003 to 2021. PATIENT SAMPLE: Adult patients admitted for radiologically confirmed diagnosis of SEA who did not initiate treatment at an outside institution. OUTCOME MEASURES: In-hospital and 90-day postdischarge mortality. METHODS: We tested the SORG stochastic gradient boosting algorithm on an independent validation cohort. We assessed its performance with discrimination, calibration, decision curve analysis, and overall performance. RESULTS: A total of 212 patients met inclusion criteria, with a short-term mortality rate of 10.4%. The area under the receiver operating characteristic curve (AUROC) of the SORG algorithm when tested on the full validation cohort was 0.82, the calibration intercept was -0.08, the calibration slope was 0.96, and the Brier score was 0.09. CONCLUSIONS: With a contemporaneous and geographically distinct independent cohort, we report successful external validation of a machine learning algorithm for prediction of in-hospital and 90-day postdischarge mortality in SEA.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Environmental Sustainability in the Orthopaedic Operating Room.

Hotter global temperatures and increasingly variable climate patterns negatively affect human health, with a wide recognition that climate change is a major global health threat. Human activities, including those conducted in the orthopaedic operating room (OR), contribute to climate change by generating greenhouse gases that trap infrared radiation from the earth's surface. This review provides an overview of the environmental effect of the orthopaedic OR and efforts to address environmental sustainability in the OR. These concepts are presented with a particular focus on patient safety and cost savings because roll-out of these efforts must be conducted with a pragmatic and patient-centered focus. Orthopaedic surgeons have an opportunity to lead efforts to improve environmental sustainability in the OR and thus contribute to efforts to curb climate change.

Attitudes and trends in the use of radiolucent spinal implants: A survey of the North American Spine Society section of spinal oncology.

Background: In spinal oncology, titanium implants pose several challenges including artifact on advanced imaging and therapeutic radiation perturbation. To mitigate these effects, there has been increased interest in radiolucent carbon fiber (CF) and CF-reinforced polyetheretherketone (CFR-PEEK) implants as an alternative for spinal reconstruction. This study surveyed the members of the North American Spine Society (NASS) section of Spinal Oncology to query their perspectives regarding the clinical utility, current practice patterns, and recommended future directions of radiolucent spinal implants. Methods: In February 2021, an anonymous survey was administered to the physicians of the NASS section of Spinal Oncology. Participation in the survey was optional. The survey contained 38 items including demographic questions as well as multiple-choice, yes/no questions, Likert rating scales, and short free-text responses pertaining to the "clinical concept", "efficacy", "problems/complications", "practice pattern", and "future directions" of radiolucent spinal implants. Results: Fifteen responses were received (71.4% response rate). Six of the participants (40%) were neurosurgeons, eight (53.3%) were orthopedic surgeons, and one was a spinal radiation oncologist. Overall, there were mixed opinions among the specialists. While several believed that radiolucent spinal implants provide substantial benefits for the detection of disease recurrence and radiation therapy options, others remained less convinced. Ongoing concerns included high costs, low availability, limited cervical and percutaneous options, and suboptimal screw and rod designs. As such, participants estimated that they currently utilize these implants for 27.3% of anterior and 14.7% of all posterior reconstructions after tumor resection. Conclusion: A survey of the NASS section of Spinal Oncology found a lack of consensus with regards to the imaging and radiation benefits, and several ongoing concerns about currently available options. Therefore, routine utilization of these implants for anterior and posterior spinal reconstructions remains low. Future investigations are warranted to practically validate these devices' theoretical risks and benefits.

A Natural History of Patients Treated Operatively and Nonoperatively for Spinal Metastases Over 2 Years Following Treatment: Survival and Functional Outcomes.

STUDY DESIGN: Prospective observational study. OBJECTIVE: We present the natural history, including survival and function, among participants in the prospective observational study of spinal metastases treatment investigation. SUMMARY OF BACKGROUND DATA: Surgical treatment has been touted as a means to preserve functional independence, quality of life, and survival. Nearly all prior investigations have been limited by retrospective design and relatively short-periods of post-treatment surveillance. METHODS: This natural history study was conducted using the records of patients who were enrolled in the prospective observational study of spinal metastases treatment study (2017-2019). Eligible participants were 18 or older and presenting for treatment of spinal metastatic disease. Patients were followed at predetermined intervals (1, 3, 6, 12, and 24-mo) following treatment. We conducted cox proportional hazard regression analysis adjusting for confounders including age, biologic sex, number of comorbidities, type of metastatic lesion, neurologic symptoms at presentation, number of metastases involving the vertebral body, vertebral body collapse, New England Spinal Metastasis Score (NESMS) at presentation, and treatment strategy. RESULTS: We included 202 patients. Twenty-three percent of the population had died by 3 months following treatment initiation, 51% by 1 year, and 70% at 2 years. There was no significant difference in survival between patients treated operatively and nonoperatively (P = 0.16). No significant difference in HRQL between groups was appreciated beyond 3 months following treatment initiation. NESMS at presentation (scores of 0 [HR 5.61; 95% CI 2.83, 11.13] and 1 [HR 3.00; 95% CI 1.60, 5.63]) was significantly associated with mortality. CONCLUSION: We found that patients treated operatively and nonoperatively for spinal metastases benefitted from treatment in terms of HRQL. Two-year mortality for the cohort as a whole was 70%. When prognosticating survival, the NESMS appears to be an effective utility, particularly among patients with scores of 0 or 1.Level of Evidence: 2.

Prospective comparison of the accuracy of the New England Spinal Metastasis Score (NESMS) to legacy scoring systems in prognosticating outcomes following treatment of spinal metastases.

BACKGROUND CONTEXT: We developed the New England Spinal Metastasis Score (NESMS) as a simple, informative, scoring scheme that could be applied to both operative and non-operative patients. The performance of the NESMS to other legacy scoring systems has not previously been compared using appropriately powered, prospectively collected, longitudinal data. PURPOSE: To compare the predictive capacity of the NESMS to the Tokuhashi, Tomita and Spinal Instability Neoplastic Score (SINS) in a prospective cohort, where all scores were assigned at the time of baseline enrollment. PATIENT SAMPLE: We enrolled 202 patients with spinal metastases who met inclusion criteria between 2017-2019. OUTCOME MEASURES: One-year survival (primary); 3-month mortality and ambulatory function at 3- and 6-months were considered secondarily. METHODS: All prognostic scores were assigned based on enrollment data, which was also assigned as time-zero. Patients were followed until death or survival at 365 days after enrollment. Survival was assessed using Kaplan-Meier curves and score performance was determined via logistic regression testing and observed to expected plots. The discriminative capacity (c-statistic) of the scoring measures were compared via the z-score. RESULTS: When comparing the discriminative capacity of the predictive scores, the NESMS had the highest c-statistic (0.79), followed by the Tomita (0.69), the Tokuhashi (0.67) and the SINS (0.54). The discriminative capacity of the NESMS was significantly greater (p-value range: 0.02 to <0.001) than any of the other predictive tools. The NESMS was also able to inform independent ambulatory function at 3- and 6-months, a function that was only uniformly replicated by the Tokuhashi score. CONCLUSIONS: The results of this prospective validation study indicate that the NESMS was able to differentiate survival to a significantly higher degree than the Tokuhashi, Tomita and SINS. We believe that these findings endorse the utilization of the NESMS as a prognostic tool capable of informing care for patients with spinal metastases.

Characterizing Health-Related Quality of Life by Ambulatory Status in Patients with Spinal Metastases.

STUDY DESIGN: Retrospective review of prospective longitudinal data. OBJECTIVE: To determine health-related quality of life (HRQL) utilities associated with specific ambulatory states in patients with spinal metastases: independent, ambulatory with assistance, and nonambulatory. SUMMARY OF BACKGROUND DATA: It is assumed that HRQL is aligned with ambulatory ability in patients with spinal metastases. Few studies have effectively considered these parameters while also accounting for clinical confounders. METHODS: We used prospective longitudinal data from patients treated at one of three tertiary medical centers (2017-2019). HRQL was characterized using the Euroquol-5-dimension (EQ5D) inventory. We performed standardized estimations of HRQL stratified by ambulatory state using generalized linear modeling that accounted for patient age at presentation, biologic sex, follow-up duration, operative or nonoperative management, and repeated measures within the same participant. RESULTS: We evaluated 675 completed EQ5D assessments, with 430 for independent ambulators, 205 for ambulators with assistance, and 40 for nonambulators. The average age of the cohort was 61.5. The most common primary cancer was lung (20%), followed by breast (18%). Forty-one percent of assessments were performed for participants treated surgically. Mortality occurred in 51% of the cohort. The standardized EQ5D utility for patients with spinal metastases and independent ambulatory function was 0.76 (95% confidence interval [CI] 0.74, 0.78). Among those ambulatory with assistance, the standardized EQ5D utility was 0.59 (95% CI 0.57, 0.61). For nonambulators, the standardized EQ5D utility was 0.14 (95% CI 0.09, 0.19). CONCLUSION: Patients with spinal metastases and independent ambulatory function have an HRQL similar to patients with primary cancers and no spinal involvement. Loss of ambulatory ability leads to a 22% decrease in HRQL for ambulation with assistance and an 82% reduction among nonambulators. Given prior studies demonstrate superior maintenance of ambulatory function with surgery for spinal metastases, our results support surgical consideration to the extent that it is clinically warranted.Level of Evidence: 3.

Albumin and Survival in Extremity Metastatic Bone Disease: An Analysis of Two Independent Datasets.

INTRODUCTION: Numerous prognostication models have been developed to estimate survival in patients with extremity metastatic bone disease, but few include albumin despite albumin's role in malnutrition and inflammation. The purpose of this study was to examine two independent datasets to determine the value for albumin in prognosticating survival in this population. MATERIALS AND METHODS: Extremity metastatic bone disease patients undergoing surgical management were identified from two independent populations. Population 1: Retrospective chart review at two tertiary care centers. Population 2: A large, national, North American multicenter surgical registry with 30-day follow-up. Bivariate and multivariate analyses were used to examine albumin's value for prognostication at 1-, 3-, and 12-month after surgery. RESULTS: In Population 1, 1,090 patients were identified with 1-, 3-, and 12-month mortality rates of 95 (8.8%), 305 (28.9%), and 639 (62.0%), respectively. In Population 2, 1,675 patients were identified with one-month postoperative mortality rates of 148 (8.8%). In both populations, hypoalbuminemia was an independent prognostic factor for mortality at 30 days. In the institutional set, hypoalbuminemia was additionally associated with 3- and 12-month mortality. CONCLUSIONS: Hypoalbuminemia is a marker for mortality in extremity metastatic bone disease. Further consideration of this marker could improve existing prognostication models in this population. LEVEL OF EVIDENCE: III.

The Cost-Effectiveness of Surgical Intervention for Spinal Metastases: A Model-Based Evaluation.

BACKGROUND: Operative and nonoperative treatments for spinal metastases are expensive interventions with a high rate of complications. We sought to determine the cost-effectiveness of a surgical procedure compared with nonoperative management as treatment for spinal metastases. METHODS: We constructed a Markov state-transition model with health states defined by ambulatory status and estimated the quality-adjusted life-years (QALYs) and costs for operative and nonoperative management of spine metastases. We considered 2 populations: 1 in which patients presented with independent ambulatory status and 1 in which patients presented with nonambulatory status due to acute (e.g., <48 hours) metastatic epidural compression. We defined the efficacy of each treatment as a likelihood of maintaining, or returning to, independent ambulation. Transition probabilities for the model, including the risks of mortality and becoming dependent or nonambulatory, were obtained from secondary data analysis and published literature. Costs were determined from Medicare reimbursement schedules. We conducted analyses over patients' remaining life expectancy from a health system perspective and discounted outcomes at 3% per year. We conducted sensitivity analyses to account for uncertainty in data inputs. RESULTS: Among patients presenting as independently ambulatory, QALYs were 0.823 for operative treatment and 0.800 for nonoperative treatment. The incremental cost-effectiveness ratio (ICER) for a surgical procedure was $899,700 per QALY. Among patients presenting with nonambulatory status, those undergoing surgical intervention accumulated 0.813 lifetime QALY, and those treated nonoperatively accumulated 0.089 lifetime QALY. The incremental cost-effectiveness ratio for a surgical procedure was $48,600 per QALY. The cost-effectiveness of a surgical procedure was most sensitive to the variability of its efficacy. CONCLUSIONS: Our data suggest that the value to society of a surgical procedure for spinal metastases varies according to the features of the patient population. In patients presenting as nonambulatory due to acute neurologic compromise, surgical intervention provides good value (ICER, $48,600 per QALY). There is a low value for a surgical procedure performed for patients who are ambulatory at presentation (ICER, $899,700 per QALY). LEVEL OF EVIDENCE: Economic and Decision Analysis Level III. See Instructions for Authors for a complete description of levels of evidence.

Evaluating ambulatory function as an outcome following treatment for spinal metastases: a systematic review.

BACKGROUND CONTEXT: Studies regarding treatment of spinal metastases are critical to evidence-based decision-making. However, variation exists in how a key outcome, ambulatory function, is assessed. PURPOSE: To characterize the sources and tools investigators have used to evaluate ambulatory function as an outcome following treatment of spinal metastases. We also sought to understand the ways ambulatory function has been conceptualized in prior studies. STUDY DESIGN: Systematic review of the literature. PATIENT SAMPLE: We identified 44 published studies for inclusion. Samples within these investigations ranged from 20 to 2,096 subjects. OUTCOME MEASURES: We describe the methods investigators have used to evaluate ambulatory function following treatment for spinal metastases. METHODS: We conducted a systematic review through PubMed, Scopus and Web of Science following PRISMA guidelines. We included studies that consisted of adult patients receiving operative or non-operative treatment for spinal metastases. We also required that study investigators specified post-treatment ambulatory function as an outcome. We recorded year of publication, study design, types of spinal metastases included in the study, treatments employed, and sample size. We also described the source (medical record, study-specific observer and/or provider, patient and/or participant), tool (standardized measure, quantitative, qualitative) and concept (eg, ambulatory vs. non-ambulatory; independent ambulation vs. ambulatory with assistance vs. non-ambulatory) used to assess ambulatory function. RESULTS: We found the plurality of studies relied on medical record documentation as their source. Amongst prospective studies, only a minority used a quantitative measure (eg, prespecified degree of walking ability) to assess ambulatory function. Most studies conceptualized ambulatory function as a dichotomized outcome, typically ambulatory versus non-ambulatory or a similar equivalent. CONCLUSIONS: Wide variation exists in how ambulatory function is defined in studies involving patients with spinal metastases. We suggest several improvements that will allow a more robust assessment of the quality and quantity of ambulatory function among patients treated for spinal metastases.

Prospective validation of a clinical prediction score for survival in patients with spinal metastases: the New England Spinal Metastasis Score.

BACKGROUND CONTEXT: The New England Spinal Metastasis Score (NESMS) was proposed as an intuitive and accessible prognostic tool for predicting survival in patients with spinal metastases. We designed an appropriately powered, prospective, longitudinal investigation to validate the NESMS. PURPOSE: To prospectively validate the NESMS. STUDY DESIGN: Prospective longitudinal observational cohort study. PATIENT SAMPLE: Patients, aged 18 and older, presenting for treatment with spinal metastatic disease. OUTCOME MEASURES: One-year mortality (primary); 6-month mortality and mortality at any time point following enrollment (secondary). METHODS: The date of enrollment was set as time zero for all patients. The NESMS was assigned based on data collected at the time of enrollment. Patients were prospectively followed to one of two predetermined end-points: death, or survival at 365 days following enrollment. Survival was visually assessed with Kaplan-Meier curves and then analyzed using multivariable logistic regression, followed by Bayesian regression to assess for robustness of point estimates and 95% confidence intervals (CI). RESULTS: This study included 180 patients enrolled between 2017 and 2018. Mortality within 1-year occurred in 56% of the cohort. Using NESMS 3 as the referent, those with a score of 2 had significantly greater odds of mortality (odds ratio 7.04; 95% CI 2.47, 20.08), as did those with a score of 1 (odds ratio 31.30; 95% CI 8.82, 111.04). A NESMS score of 0 was associated with perfect prediction, as 100% of individuals with this score were deceased at 1-year. Similar determinations were encountered for mortality at 6-months and overall. CONCLUSIONS: This study validates the NESMS and demonstrates its utility in prognosticating survival for patients with spinal metastatic disease, irrespective of selected treatment strategy. This is the first study to prospectively validate a prognostic utility for patients with spinal metastases. The NESMS can be directly applied to patient care, hospital-based practice and health-care policy.

Diagnoses, treatment, and oncologic outcomes in patients with calcaneal malignances: Case series, systematic literature review, and pooled cohort analysis.

BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge. AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors. METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage. RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07). CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.

Serum alkaline phosphatase is a prognostic marker in bone metastatic disease of the extremity.

PURPOSE: The purpose of this study was to determine the prognostic value of serum alkaline phosphatase for treatment decision making in metastatic bone disease. METHODS: 1090 patients who underwent surgery for extremity metastatic disease were retrospectively identified at two tertiary care centers. The association between alkaline phosphatase and mortality was assessed by bivariate and multivariate analyses. RESULTS: Three-month and one-year mortality rates were 305 (29%) and 639 (62%), respectively. Alkaline phosphatase was associated with mortality at both three months and one year. CONCLUSION: Serum alkaline phosphatase may be a useful marker in prognostic algorithms for patients with extremity metastatic disease.

The Prognostic Value of Laboratory Markers and Ambulatory Function at Presentation for Post-Treatment Morbidity and Mortality Following Epidural Abscess.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop a comprehensive understanding of the prognostic value of laboratory markers on morbidity and mortality following epidural abscess. SUMMARY OF BACKGROUND DATA: Spinal epidural abscess is a serious medical condition with high rates of morbidity. The value of laboratory data in forecasting morbidity and mortality after epidural abscess remains underexplored. METHODS: We obtained clinical data on patients treated for epidural abscess at two academic centers from 2005 to 2017. Our primary outcome was the development of one or more complications within 90-days of presentation, with mortality a secondary measure. Primary predictors included serum albumin, serum creatinine, platelet-lymphocyte ratio, and ambulatory status at presentation. We used multivariable logistic regression techniques to adjust for confounders. The most parsimonious set of variables influencing both complications and mortality were considered to be clinically significant. These were then examined individually and in combination to assess for synergy along with model-discrimination and calibration. We performed internal validation with a bootstrap procedure using sampling with replacement. RESULTS: We included 449 patients in this analysis. Complications were encountered in 164 cases (37%). Mortality within 1-year occurred in 39 patients (9%). Regression testing determined that serum albumin, serum creatinine, and ambulatory status at presentation were clinically important predictors of outcome, with albumin more than 3.5 g/dL, creatinine less than or equal to 1.2 mg/dL, and independent ambulatory function at presentation considered favorable characteristics. Patients with no favorable findings had increased likelihood of 90-day complications (odds ratio [OR] 5.43; 95% confidence intervals [CI] 1.98, 14.93) and 1-year mortality (OR 8.94; 95% CI 2.03, 39.37). Those with one favorable characteristic had greater odds of complications (OR 4.00; 95% CI 2.05, 7.81) and mortality (OR 5.71; 95% CI 1.60, 20.43). CONCLUSION: We developed a nomogram incorporating clinical and laboratory values to prognosticate outcomes after treatment for epidural abscess. The results can be used in shared-decision making and counseling. LEVEL OF EVIDENCE: 3.

Survival After Surgery for Renal Cell Carcinoma Metastatic to the Spine: Impact of Modern Systemic Therapies on Outcomes.

BACKGROUND: Modern medical management of metastatic renal cell carcinoma (RCC) includes therapies targeting tyrosine kinases, growth pathways (mammalian target of rapamycin (mTOR)), and immune checkpoints. OBJECTIVE: To test our hypothesis that patients with spinal metastases would benefit from postoperative systemic therapy despite presenting with disease that, in many cases, was resistant to prior systemic therapy. METHODS: This is an Institutional Review Board-approved clinical retrospective cohort analysis. A sample of adult patients with RCC metastatic to the spine who underwent operative intervention between January 2010 and December 2017 at 2 large academic medical centers was used in this study. RESULTS: We identified 78 patients with metastatic RCC in whom instrumented stabilization was performed in 79% and postoperative stereotactic radiosurgery was performed in 41% of patients. Of patients presenting with weakness or myelopathy, 93% noted postoperative improvement and 78% reported improvement in radicular and axial paraspinal pain severity. Increased overall survival (OS) (913 d (95% CI: 633-1975 d, n = 49) vs 222 d (95% CI: 143-1005 d, n = 29), P = .003) following surgery was noted in patients who received postoperative systemic therapy a median of 80 d (interquartile range 48-227 d) following the surgical intervention. CONCLUSION: Postoperative outcomes and palliation of symptoms for metastatic RCC without targeted therapies in this cohort are similar to those reported in earlier series prior to the adoption of these systemic therapies. We observed a significantly longer OS among patients who received modern systemic therapies postoperatively. These findings have implications for the preoperative evaluation of patients with systemic disease who may have been deemed poor surgical candidates prior to the availability of these systemic therapies.

Development and Internal Validation of Machine Learning Algorithms for Preoperative Survival Prediction of Extremity Metastatic Disease.

BACKGROUND: A preoperative estimation of survival is critical for deciding on the operative management of metastatic bone disease of the extremities. Several tools have been developed for this purpose, but there is room for improvement. Machine learning is an increasingly popular and flexible method of prediction model building based on a data set. It raises some skepticism, however, because of the complex structure of these models. QUESTIONS/PURPOSES: The purposes of this study were (1) to develop machine learning algorithms for 90-day and 1-year survival in patients who received surgical treatment for a bone metastasis of the extremity, and (2) to use these algorithms to identify those clinical factors (demographic, treatment related, or surgical) that are most closely associated with survival after surgery in these patients. METHODS: All 1090 patients who underwent surgical treatment for a long-bone metastasis at two institutions between 1999 and 2017 were included in this retrospective study. The median age of the patients in the cohort was 63 years (interquartile range [IQR] 54 to 72 years), 56% of patients (610 of 1090) were female, and the median BMI was 27 kg/m (IQR 23 to 30 kg/m). The most affected location was the femur (70%), followed by the humerus (22%). The most common primary tumors were breast (24%) and lung (23%). Intramedullary nailing was the most commonly performed type of surgery (58%), followed by endoprosthetic reconstruction (22%), and plate screw fixation (14%). Missing data were imputed using the missForest methods. Features were selected by random forest algorithms, and five different models were developed on the training set (80% of the data): stochastic gradient boosting, random forest, support vector machine, neural network, and penalized logistic regression. These models were chosen as a result of their classification capability in binary datasets. Model performance was assessed on both the training set and the validation set (20% of the data) by discrimination, calibration, and overall performance. RESULTS: We found no differences among the five models for discrimination, with an area under the curve ranging from 0.86 to 0.87. All models were well calibrated, with intercepts ranging from -0.03 to 0.08 and slopes ranging from 1.03 to 1.12. Brier scores ranged from 0.13 to 0.14. The stochastic gradient boosting model was chosen to be deployed as freely available web-based application and explanations on both a global and an individual level were provided. For 90-day survival, the three most important factors associated with poorer survivorship were lower albumin level, higher neutrophil-to-lymphocyte ratio, and rapid growth primary tumor. For 1-year survival, the three most important factors associated with poorer survivorship were lower albumin level, rapid growth primary tumor, and lower hemoglobin level. CONCLUSIONS: Although the final models must be externally validated, the algorithms showed good performance on internal validation. The final models have been incorporated into a freely accessible web application that can be found at https://sorg-apps.shinyapps.io/extremitymetssurvival/. Pending external validation, clinicians may use this tool to predict survival for their individual patients to help in shared treatment decision making. LEVEL OF EVIDENCE: Level III, therapeutic study.