Search

BACKGROUND The outcome differences following surgery for an impending versus a completed pathological fracture have not been clearly defined. The purpose of the present study was to assess differences in outcomes following the surgical treatment of impending versus completed pathological fractures in patients with long-bone metastases in terms of (1) 90-day and 1-year survival and (2) intraoperative blood loss, perioperative blood transfusion, anesthesia time, duration of hospitalization, 30-day postoperative systemic complications, and reoperations. METHODS We retrospectively performed a matched cohort study utilizing a database of 1,064 patients who had undergone operative treatment for 462 impending and 602 completed metastatic long-bone fractures. After matching on 22 variables, including primary tumor, visceral metastases, and surgical treatment, 270 impending pathological fractures were matched to 270 completed pathological fractures. The primary outcome was assessed with the Cox proportional hazard model. The secondary outcomes were assessed with the McNemar test and the Wilcoxon signed-rank test. RESULTS The 90-day survival rate did not differ between the groups (HR, 1.13 [95% CI, 0.81 to 1.56]; p = 0.48), but the 1-year survival rate was worse for completed pathological fractures (46% versus 38%) (HR, 1.28 [95% CI, 1.02 to 1.61]; p = 0.03). With regard to secondary outcomes, completed pathological fractures were associated with higher intraoperative estimated blood loss (p = 0.03), a higher rate of perioperative blood transfusions (p = 0.01), longer anesthesia time (p = 0.04), and more reoperations (OR, 2.50 [95% CI, 1.92 to 7.86]; p = 0.03); no differences were found in terms of the rate of 30-day postoperative complications or the duration of hospitalization. CONCLUSIONS Patients undergoing surgery for impending pathological fractures had lower 1-year mortality rates and better secondary outcomes as compared with patients undergoing surgery for completed pathological fractures when accounting for 22 covariates through propensity matching. Patients with an impending pathological fracture appear to benefit from prophylactic stabilization as stabilizing a completed pathological fracture seems to be associated with increased mortality, blood loss, rate of blood transfusions, duration of surgery, and reoperation risk. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. QUESTIONS/PURPOSES (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? METHODS All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. RESULTS The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. CONCLUSION SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE Level III, therapeutic study.

BACKGROUND CONTEXT Patient-Reported Outcome Measurement Information System (PROMIS) scores are increasingly utilized in clinical care. However, it is unclear if PROMIS can discriminate surgeon performance on an individual level. PURPOSE The purpose of this study was to examine surgeon-level variance in rates of achieving minimal clinically important difference (MCID) after lumbar decompression. PATIENT SAMPLE This is a prospective, observational cohort study performed across a healthcare enterprise (two academic medical centers and three community centers). Patients 18 years or older undergoing one- to two-level primary decompression for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) were included. OUTCOME MEASURES The primary outcome was achievement of MCID, using a distribution-based method, on paired PROMIS physical function scores. METHODS Descriptive statistics were generated to examine the baseline characteristics of the study cohort. Bivariate analyses were used to examine the impact of surgeon-level variance on rates of MCID. Multivariable analyses were used to examine the risk-adjusted impact of surgeon-level variance on rates of MCID. RESULTS Overall, 636 patients treated by nine surgeons were included. The median patient age was 58 [interquartile range (IQR): 46–70] and 62.3% (n=396) were female. Among all patients, 56.9% (n=362) underwent surgery for LDH. The overall rate of achieving MCID was 75.8% (n=482). Of the surgeons, the median years in practice were 12 (range 4–31) and 55.6% (n=5) were in academic practice settings. On bivariate analysis, patients treated by one of the surgeons had lower rates of achieving MICD (odds ratio=0.37, 95% confidence interval: 0.15–0.91, p=.03). However, on multivariable analysis adjusting for operative indication (LDH vs. LSS), body mass index, number of comorbidities, percent unemployment in patient zip code, and preoperative PROMIS physical function scores, all surgeons were equally likely to obtain MCID. CONCLUSIONS In this cohort, variance in PROMIS scores after primary lumbar decompression is influenced by patient-related factors and not by individual surgeon. Adequate risk adjustment is needed if ascertaining clinical improvement on an individual surgeon basis. Level of Evidence 2

BACKGROUND Patients with bone metastases often are unable to complete quality of life (QoL) questionnaires, and cohabitants (such as spouses, domestic partners, offspring older than 18 years, or other people who live with the patient) could be a reliable alternative. However, the extent of reliability in this complicated patient population remains undefined, and the influence of the cohabitant's condition on their assessment of the patient's QoL is unknown. QUESTIONS/PURPOSES (1) Do QoL scores, measured by the 5-level EuroQol-5D (EQ-5D-5L) version and the Patient-reported Outcomes Measurement Information System (PROMIS) version 1.0 in three domains (anxiety, pain interference, and depression), reported by patients differ markedly from scores as assessed by their cohabitants? (2) Do cohabitants' PROMIS-Depression scores correlate with differences in measured QoL results? METHODS This cross-sectional study included patients and cohabitants older than 18 years of age. Patients included those with presence of histologically confirmed bone metastases (including lymphoma and multiple myeloma), and cohabitants must have been present at the clinic visit. Patients were eligible for inclusion in the study regardless of comorbidities, prognosis, prior surgery, or current treatment. Between June 1, 2016 and March 1, 2017 and between October 1, 2017 and February 26, 2018, all 96 eligible patients were approached, of whom 49% (47) met the selection criteria and were willing to participate. The included 47 patient-cohabitant pairs independently completed the EQ-5D-5L and the eight-item PROMIS for three domains (anxiety, pain, and depression) with respect to the patients' symptoms. The cohabitants also completed the four-item PROMIS-Depression survey with respect to their own symptoms. RESULTS There were no clinically important differences between the scores of patients and their cohabitants for all questionnaires, and the agreement between patient and cohabitant scores was moderate to strong (Spearman correlation coefficients ranging from 0.52 to 0.72 on the four questionnaires; all p values < 0.05). However, despite the good agreement in QoL scores, an increased cohabitant's depression score was correlated with an overestimation of the patient's symptom burden for the anxiety and depression domains (weak Spearman correlation coefficient of 0.33 [95% confidence interval 0.08 to 0.58]; p = 0.01 and moderate Spearman correlation coefficient of 0.52 [95% CI 0.29 to 0.74]; p < 0.01, respectively). CONCLUSION The present findings support that cohabitants might be reliable raters of the QoL of patients with bone metastases. However, if a patient's cohabitant has depression, the cohabitant may overestimate a patient's symptoms in emotional domains such as anxiety and depression, warranting further research that includes cohabitants with and without depression to elucidate the effect of depression on the level of agreement. For now, clinicians may want to reconsider using the cohabitant's judgement if depression is suspected. CLINICAL RELEVANCE These findings suggest that a cohabitant's impressions of a patient's quality of life are, in most instances, accurate; this is potentially helpful in situations where the patient cannot weigh in. Future studies should employ longitudinal designs to see how or whether our findings change over time and with disease progression, and how specific interventions-like different chemotherapeutic regimens or surgery-may factor in.

Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-κB ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell-rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell-rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.

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.

BACKGROUND Adult spinal deformity (ASD) is a debilitating condition that commonly requires surgical intervention. However, ASD patients may also present with osteoporosis, predisposing them to surgical complications and failure of instrumentation. As a result, proper detection of low bone mineral density (BMD) is critical in order to ensure proper patient care. Typically dual-energy x-ray absorptiometry (DEXA) scans are performed on the hip and spine. Unfortunately, in ASD patients, the latter is often inaccurate PURPOSE In this study, we consider the value of obtaining a forearm DEXA scan in addition to a hip scan in patients suffering from ASD and osteoporosis in order to accurately detect low BMD. STUDY DESIGN Retrospective study. PATIENT SAMPLE Patient data between 2016 and 2018 from a single academic medical center was utilized. Two hundred eighty-six patients met the initial search criteria. OUTCOME MEASURES No outcomes measures related to self-reporting, physiology, or functionality were evaluated in this study. Primary outcome measures analyzed included T-scores across various anatomic locations and diagnoses relating to low bone density (ie, osteopenia and osteoporosis). METHODS This retrospective study examines patients that underwent DEXA studies between 2016 and 2018 and were previously diagnosed with both osteoporosis and adult spinal deformity. For each patient, age, gender, body mass index, and smoking history were noted, as well as whether there was long-term prednisone use. T-scores from both the forearm and hip were recorded and analyzed. Diagnoses from hip DEXA scans were compared with those obtained from forearm scans to identify which region was more sensitive in detecting low BMD. From this data, the frequency of a missed diagnosis, due to reliance on hip or spine T-scores for detection of low BMD, was extrapolated. No external funding source was received in support of this study. RESULTS Two hundred eighty-six patients matched the initial search criteria. Only 68% had one T-score value. However, 24.8% of patients had data for both the hip and forearm, whereas 7.1% had data for the forearm, hip, and spine. Among the 85 patients with more than one anatomical site of study, the forearm was more sensitive than the hip in its ability to detect osteopenia or osteoporosis 41.2% of the time. A two-tailed t test showed no statistically significant difference between hip T-scores and forearm T-scores. However, for more than 17% of patients, the forearm allowed clinicians to detect osteoporosis or osteopenia in a setting where using only the hip data would have missed such a diagnosis. CONCLUSIONS Clinicians need to ensure they survey at least two locations when conducting DEXA studies before precluding a diagnosis of osteopenia or osteoporosis. All ASD patients being evaluated for low bone density should receive DEXA scans that survey at least the hip and the forearm. Misdiagnoses can be costly in the setting of ASD. They occur frequently when only a single hip scan is relied upon to assess BMD.

BACKGROUND CONTEXT Preoperative survival estimation in spinal metastatic disease helps determine the appropriateness of invasive management. The SORG ML 90-day and 1-year machine learning algorithms for survival in spinal metastatic disease were previously developed in a single institutional sample but remain to be externally validated. PURPOSE The purpose of this study was to externally validate these algorithms in an independent population from another institution. STUDY DESIGN/SETTING Retrospective study at a large, tertiary care center. PATIENT SAMPLE Patients 18 years or older who underwent surgery between 2003 and 2016. OUTCOME MEASURES Ninety-day and 1-year mortality. METHODS Baseline characteristics of the validation cohort were compared to the developmental cohort for the SORG ML algorithms. Discrimination (c-statistic and receiver operating curve), calibration (calibration slope, intercept, calibration plot, and observed proportions by predicted risk groups), overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithms in the validation cohort. RESULTS Overall, 176 patients underwent surgery for spinal metastatic disease, of which 44 (22.7%) experienced 90-day mortality and 99 (56.2%) experienced 1-year mortality. The validation cohort differed significantly from the developmental cohort on primary tumor histology, metastatic tumor burden, previous systemic therapy, overall comorbidity burden, and preoperative laboratory characteristics. Despite these differences, the SORG ML algorithms generalized well to the validation cohort on discrimination (c-statistic 0.75–0.81 for 90-day mortality and 0.77–0.78 for 1-year mortality), calibration, Brier score, and decision curve analysis. CONCLUSION and RELEVANCE Initial results from external validation of the SORG ML 90-day and 1-year algorithms for survival prediction in spinal metastatic disease suggest potential utility of these digital decision aids in clinical practice. Further studies are needed to validate or refute these algorithms in large patient samples from prospective, international, multi-institutional trials.

BACKGROUND CONTEXT: Laboratory values have been found to be useful predictive measures of survival following surgery. The utility of laboratory values for prognosticating outcomes among patients with spinal metastases has not been studied. PURPOSE: To determine the prognostic capacity of laboratory values at presentation including white blood cell (WBC) count, serum albumin and platelet-lymphocyte ratio (PLR) in patients with spinal metastases. STUDY DESIGN: Retrospective review of records from two tertiary care centers (2005–2017). PATIENT SAMPLE: Patients, aged 40–80, who received operative or non-operative management for spinal metastases. OUTCOME MEASURES: Survival, complications or hospital readmissions within 90 days of treatment and a composite measure for treatment failure accounting for changes in ambulatory function and mortality at 6-months following presentation. METHODS: Multivariable Cox proportional hazard regression analysis was used to analyze the relationship between laboratory values and length of survival, adjusting for confounders. Multivariable logistic regression was used in analyses related to 6-month and 1-year mortality, complications, readmissions and treatment failure. A scoring rubric was developed based on the performance of laboratory values in the multivariable tests. Internal validation was performed using a bootstrap simulation that consisted of sampling with replacement and 1,000 replications. RESULTS: We included 1,216 patients. Thirty-seven percent of patients received a surgical intervention and 63% were treated non-operatively. Median survival for the cohort as a whole was 255 days (inter-quartile range 93–642 days). PLR (HR 1.53; 95% CI 1.29, 1.80; p

Background Context In-hospital and short-term mortality in patients with spinal epidural abscess (SEA) remains unacceptably high despite diagnostic and therapeutic advancements. Forecasting this potentially avoidable consequence at the time of admission could improve patient management and counseling. Few studies exist to meet this need, and none have explored methodologies such as machine learning. Purpose The purpose of this study was to develop machine learning algorithms for prediction of in-hospital and 90-day postdischarge mortality in SEA. Study Design/Setting Retrospective, case-control study at two academic medical centers and three community hospitals from 1993 to 2016. Patients Sample Adult patients with an inpatient admission for radiologically confirmed diagnosis of SEA. Outcome Measures In-hospital and 90-day postdischarge mortality. Methods Five machine learning algorithms (elastic-net penalized logistic regression, random forest, stochastic gradient boosting, neural network, and support vector machine) were developed and assessed by discrimination, calibration, overall performance, and decision curve analysis. Results Overall, 1,053 SEA patients were identified in the study, with 134 (12.7%) experiencing in-hospital or 90-day postdischarge mortality. The stochastic gradient boosting model achieved the best performance across discrimination, c-statistic=0.89, calibration, and decision curve analysis. The variables used for prediction of 90-day mortality, ranked by importance, were age, albumin, platelet count, neutrophil to lymphocyte ratio, hemodialysis, active malignancy, and diabetes. The final algorithm was incorporated into a web application available here: https://sorg-apps.shinyapps.io/seamortality/ . Conclusions Machine learning algorithms show promise on internal validation for prediction of 90-day mortality in SEA. Future studies are needed to externally validate these algorithms in independent populations.

BACKGROUND CONTEXT Data regarding risk of failure of nonoperative management in spinal epidural abscess (SEA) are limited. Given the potential for deterioration with treatment failure, a tool that predicts the probability of failure would be of great clinical utility. PURPOSE We primarily aim to build a machine learning model using independent predictors of nonoperative management failure. Secondarily, we aim to develop an open-access web-based application that provides a patient-specific probability of treatment failure. STUDY DESIGN/SETTING Retrospective, case-control study. PATIENT SAMPLE Patients 18 years or older diagnosed with SEA at 2 academic medical centers and 3 community hospitals. OUTCOME MEASURES Failure of nonoperative management. METHODS This is a retrospective cohort study of 367 patients with SEA initially managed nonoperatively between 1993 and 2016. The primary outcome was failure of nonoperative management defined as neurologic deterioration, worsened back and/or radicular pain, or persistent symptoms despite initiation of antibiotic therapy. Five machine learning algorithms were developed and assessed by discrimination, calibration, and overall performance. RESULTS Ninety-nine (27%) patients failed nonoperative management. Factors determined for prediction of nonoperative management were: motor deficit, diabetes, ventral component of abscess relative to thecal sac, history of compression or pathologic vertebral fracture, sensory deficit, active malignancy, and involvement of 3 or more vertebral levels. The elastic-net penalized logistic regression model was chosen as the final model given its superior discrimination, calibration, and overall model performance. This model was incorporated into an open access web application. CONCLUSION By building a discriminative and well-calibrated model in a user-friendly and open-access digital interface, we hope to provide a prognostic tool that can be used to inform clinical decision-making in real-time.

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio have been previously identified as markers for overall survival in oncology but remain heretofore unexplored in spinal epidural abscess (SEA).The purpose of this study was to determine the impact of these routinely collected assessments on 90-day mortality in SEA.Retrospective, case-control study.Patients 18 years or older diagnosed with SEA at 2 academic medical centers and 3 community hospitals.Ninety-day postdischarge and in-hospital mortality.Complete blood count with differential obtained on the day immediately preceding or on the day of admission was used to calculate platelet to lymphocyte and neutrophil to lymphocyte ratios. Multivariate analyses were used to determine if these ratios were independent risk factors for 90-day mortality.For 1,053 SEA patients included in the study, the rate of 90-day mortality was 134 (12.7%). The rate of 90-day mortality with neutrophil to lymphocyte ratio (≥8) was (20.5%) compared to (8.1%) with neutrophil to lymphocyte ratio8. Neutrophil to lymphocyte ratio was positively associated with bacteremia, elevated erythrocyte sedimentation rate, and concurrent systemic infections (endocarditis, meningitis) and negatively associated with duration of symptoms prior to presentation. On multivariate analysis, elevated neutrophil to lymphocyte remained an independent risk factor for 90-day mortality (odds ratio=2.62, 95% confidence interval=1.66-4.17, p.001). Platelet to lymphocyte ratio was not associated with 90-day mortality.Absolute neutrophil to lymphocyte ratio is a routinely collected but overlooked biomarker in patients with spinal epidural abscess that is a novel independent risk factor for 90-day mortality.

Objectives: To assess the impact of surgical intervention on survival, ambulatory capacity, complications and readmissions following treatment for lumbar metastases. Patients and Methods: We identified all adult patients treated for lumbar metastases between 2005−2017. To limit the potential for inherent bias to influence determinations, we used principal component analysis to identify confounders to be included in multivariable testing. Multivariable logistic regression was performed, followed by Bayesian analysis to generate conservative estimates of effect size and 95% confidence intervals (CI). In a sensitivity test, analyses were repeated in a population where patients who died before they could initiate treatment were excluded. Results: In the period under study, we identified 571 patients who met inclusion criteria. Twenty-one percent of the cohort received a surgical intervention. Bayes regression indicated surgical intervention was independently associated with decreased mortality at 6-months (odds ratio [OR] 0.49; 95% CI 0.34, 0.68) and 1-year (OR 0.63; 95% CI 0.51, 0.76), along with lower odds of being non-ambulatory at 6-months following presentation (OR 0.29; 95% CI 0.18, 0.45). Surgery was also associated with increased odds of complications (OR 1.60; 95% CI 1.24, 2.06) and readmissions (OR 1.37; 95% CI 1.09, 1.72). Numerous clinical characteristics were found to be associated with the outcomes of interest including serum albumin, lung metastases and vertebral body collapse. Conclusions: Given the favorable outcomes associated with the incorporation of surgery as a component of treatment, we believe that such interventions may be considered part of the treatment approach in patients with lumbar metastases.

BACKGROUND: Patient reported outcome data in bone metastatic disease are scarce and it would be useful to have normative data and understand what patients are at risk for poor function and more pain. OBJECTIVES: We aimed to assess what factors are independently associated with physical function and pain intensity in patients with bone metastasis. METHODS: We included data from 211 patients with bone metastasis who completed a survey (2014-2016) including the PROMIS Physical Function Cancer and PROMIS Pain Intensity questionnaires. RESULTS: Prostate (P

Purpose: An excessive amount of total hospitalization is caused by delays due to patients waiting to be placed in a rehabilitation facility or skilled nursing facility (RF/SNF). An accurate preoperative prediction of who would need a RF/SNF place after surgery could reduce costs and allow more efficient organizational planning. We aimed to develop a machine learning algorithm that predicts non-home discharge after elective surgery for lumbar spinal stenosis. Methods: We used the American College of Surgeons National Surgical Quality Improvement Program to select patient that underwent elective surgery for lumbar spinal stenosis between 2009 and 2016. The primary outcome measure for the algorithm was non-home discharge. Four machine learning algorithms were developed to predict non-home discharge. Performance of the algorithms was measured with discrimination, calibration, and an overall performance score. Results: We included 28,600 patients with a median age of 67 (interquartile range 58–74). The non-home discharge rate was 18.2%. Our final model consisted of the following variables: age, sex, body mass index, diabetes, functional status, ASA class, level, fusion, preoperative hematocrit, and preoperative serum creatinine. The neural network was the best model based on discrimination (c-statistic = 0.751), calibration (slope = 0.933; intercept = 0.037), and overall performance (Brier score = 0.131). Conclusions: A machine learning algorithm is able to predict discharge placement after surgery for lumbar spinal stenosis with both good discrimination and calibration. Implementing this type of algorithm in clinical practice could avert risks associated with delayed discharge and lower costs. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].

BACKGROUND The prediction of survival is valuable to optimize treatment of metastatic long-bone disease. The Skeletal Oncology Research Group (SORG) machine-learning (ML) algorithm has been previously developed and internally validated. The purpose of this study was to determine if the SORG ML algorithm accurately predicts 90-day and 1-year survival in an external metastatic long-bone disease patient cohort. METHODS A retrospective review of 264 patients who underwent surgery for long-bone metastases between 2003 and 2019 was performed. Variables used in the stochastic gradient boosting SORG algorithm were age, sex, primary tumor type, visceral/brain metastases, systemic therapy, and 10 preoperative laboratory values. Model performance was calculated by discrimination, calibration, and overall performance. RESULTS The SORG ML algorithms retained good discriminative ability (area under the cure [AUC]: 0.83; 95% confidence interval [CI]: 0.76-0.88 for 90-day mortality and AUC: 0.84; 95% CI: 0.79-0.88 for 1-year mortality), calibration, overall performance, and decision curve analysis. CONCLUSION The previously developed ML algorithms demonstrated good performance in the current study, thereby providing external validation. The models were incorporated into an accessible application (https://sorg-apps.shinyapps.io/extremitymetssurvival/) that may be freely utilized by clinicians in helping predict survival for individual patients and assist in informative decision-making discussion before operative management of long bone metastatic lesions.

Sarcoma diagnosis has become increasingly complex, requiring a combination of morphology, immunohistochemistry, and molecular studies to derive specific diagnoses. We evaluated the role of anchored multiplex polymerase chain reaction-based gene fusion assay in sarcoma diagnostics. Between 2015 and 2018, bone and soft tissue sarcomas with fusion assay results were compared with the histologic diagnosis. Of 143 sarcomas tested for fusions, 43 (30%) had a detectable fusion. In review, they could be classified into 2 main categories: (1) 31 tumors with concordant morphologic and fusion data; and (2) 12 tumors where the fusion panel identified an unexpected rearrangement that played a significant role in classification. The overall concordance of the fusion assay results with morphology/immunohistochemistry or alternate confirmatory molecular studies was 83%. Collectively, anchored multiplex polymerase chain reaction-based solid fusion assay represents a robust means of detecting targeted fusions with known and novel partners. The predictive value of the panel is highest in tumors that show a monomorphic cell population, round cell tumors, as well as tumors rich in inflammatory cells. However, with an increased ability to discover fusions of uncertain significance, it remains essential to emphasize that the diagnosis of bone and soft tissue neoplasms requires the integration of morphology and immunohistochemical profile with these molecular methods, for accurate diagnosis and optimal clinical management of sarcomas.

Background and objectives The subtypes of surface osteosarcomas include well-differentiated, low-grade parosteal osteosarcoma (POS), intermediate-grade periosteal osteosarcoma (PerOS), high-grade surface osteosarcoma (HGSO), and high-grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease-specific survival (DSS). We identify outcome predictive factors and report functional results. Methods This retrospective study evaluated patients with primary surface osteosarcoma at our hospital from 1992 to 2019. Fifty-one patients had a median follow-up of 6.1 years (range: 0.1-25.2). Histologic subtypes included 32 POS, 11 PerOS, 4 HGSO, and 3 dPOS. Bone and soft tissue margins were classified using the American Joint Committee on Cancer residual tumor classification (Rx = Not evaluable; R0 = negative margin; R1 = microscopic positive margin; and R2 = macroscopic positive margin) and the modified R classification (mRx = not evaluable; mR0 = negative margin >1 mm; mR1 = negative margin ≤1 mm; mR1-dir: Positive microscopic margin locally; mR2a: Positive macroscopic margin locally; mR2b: positive macroscopic margin distally; and mR2C: positive macroscopic margin locally and distally). Forty-one patients had functional outcomes. Results Three POS patients developed recurrence: two had R0 margins and one an intralesional resection. Five patients developed lung metastases (POS: 3, dPOS: 2). Four patients died. The only significant disease progression predictor was age. OS at 10 years was 97%. 48 patients had negative bone margins (R0 or mR0 and mR1) and 47 patients had negative soft-tissue margins (R0 or mR0 and mR1). The average MSTS score was 88.43 (range: 34.29-100). Conclusions We advocate surgery for POS and believe R0 (mR0 and mR1 resections) or planned R1 (mR1-dir) to preserve function are acceptable. We favor chemotherapy and surgery for PerOS, though a chemotherapeutic response is highly variable. High-grade tumors are the most infrequent subtype, but HGSO and dPOS seem to portend a poorer prognosis. Good function can be obtained.

BACKGROUND CONTEXT: Although survival of patients with spinal metastases has improved over the last decades due to advances in multi-modal therapy, there are currently no reliable predictors of mortality. Body composition measurements obtained using computed tomography (CT) have been recently proposed as biomarkers for survival in patients with and without cancer. Patients with cancer routinely undergo CT for staging or surveillance of therapy. Body composition assessed using opportunistic CTs might be used to determine survival in patients with spinal metastases. PURPOSE: The purpose of this study was to determine the value of body composition measures obtained on opportunistic abdomen CTs to predict 90-day and 1-year mortality in patients with spinal metastases undergoing surgery. We hypothesized that low muscle and abdominal fat mass were positive predictors of mortality. STUDY DESIGN: Retrospective study at a single tertiary care center in the United States. PATIENT SAMPLE: This retrospective study included 196 patients between 2001 and 2016 that were 18 years of age or older, underwent surgical treatment for spinal metastases, and had a preoperative CT of the abdomen within three months prior to surgery. OUTCOME MEASURES: 90-day and 1-year mortality by any cause. METHODS: Quantification of cross-sectional areas (CSA) and CT attenuation of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and paraspinous and abdominal skeletal muscle were performed on CT images at the level of L4 using an in-house automated algorithm. Sarcopenia was determined by total muscle CSA (cm(2)) divided by height squared (m(2)) with cutoff values of

BACKGROUND CONTEXT Incidental durotomy during elective spine surgery is relatively common. While usually benign and self-limited, it can be associated with morbidity, increased cost, and medicolegal ramifications. Dural repair typically involves performing a primary closure using a suture or dural staple; repairs are then frequently augmented with a sealant, patch, or fat/fascial graft. Although primary repair of an incidental durotomy is standard practice, the ideal secondary sealant or augment choice remains unclear. A wide variety of commercially available dural sealant options exist, and while none have demonstrated consistent superiority, all are associated with single-use costs in the hundreds to thousands of dollars and have concerns regarding swelling, local inflammation, or short-lived dural adherence. PURPOSE The goal of this study is to compare the results of dural repair augmentation using an open intraoperative epidural blood patch to a hydrogel technique. STUDY DESIGN/SETTING Retrospective comparative cohort study at an academic referral center PATIENT SAMPLE Adult patients undergoing lumbar spine surgery from March 2017 to January 2021 who sustained an incidental durotomy. Patients undergoing surgery for infection were excluded. OUTCOME MEASURES The primary outcome was failure of the repair as determined by a return to the operating room for re-exploration of a persistent cerebrospinal fluid (CSF) leak within 30 days of the index procedure. A secondary outcome was the incidence of a postoperative positional headache, and if present, the method used to obtain resolution. The primary predictor was use of a suture and hydrogel technique (“hydrogel” group), or the use of an epidural blood patch (“EBP” group). METHODS The method for applying an open epidural blood patch is presented in detail and involves primarily repairing the durotomy followed by allowing whole blood to pool and clot in the operative field until the durotomy is completely covered. This was compared with a group of patients undergoing secondary augmentation with commercially available hydrogel. In both groups, mechanical resistance to CSF leakage was confirmed with direct visualization and a Valsalva maneuver, respectively. Patients were instructed to remain flat until the morning after surgery. Chart review was used for data abstraction on preoperative, demographic, perioperative, and postoperative clinical factors. To compare between the hydrogel and EBP group, Wilcoxon rank-sum testing was used to test for non-parametric comparisons of means, and chi-square testing between binomial data. RESULTS Of 732 patients during the study period, forty-eight patients met study criteria. Twenty-five patients were in the hydrogel group and 23 in the EBP group. Mean age was 69.3 years (standard error 1.3 years). Patients were predominantly female (n = 31, 64.6%) with a mean BMI of 29.5 (SE 0.8), with no significant baseline differences between the hydrogel and EBP groups. Two patients in the hydrogel group (8.0%) and two in the EBP group (8.7%) had mild positional headaches postoperatively that resolved without intervention within 24 hours. One (4.3%) patient in the EBP group had positional headaches following an initial headache-free period; this patient was returned to the operating room and no evidence of a persistent CSF leak was found despite meticulous exploration. CONCLUSIONS An open, intraoperatively placed epidural blood patch may be an efficacious and cost-effective way to manage an incidental durotomy. This method merits further study as an allergy-free, no swell, cost-neutral method of dural repair augmentation.

Background Predicting survival in myxoid liposarcoma (MLS) patients is very challenging given its propensity to metastasize and the controversial role of adjuvant therapy. The purpose of this study was to develop a machine-learning algorithm for the prediction of survival at five years for patients with MLS and externally validate it using our institutional cohort. Methods Two databases, the surveillance, epidemiology, and end results program (SEER) database and an institutional database, were used in this study. Five machine learning models were created based on the SEER database and performance was rated using the TRIPOD criteria. The model that performed best on the SEER data was again tested on our institutional database. Results The net-elastic penalized logistic regression model was the best according to our performance indicators. This model had an area under the curve (AUC) of 0.85 when compared to the SEER testing data and an AUC of 0.76 when tested against institutional database. An application to use this calculator is available at https://sorg-apps.shinyapps.io/myxoid_liposarcoma/. Conclusion MLS is a soft-tissue sarcoma with adjunct treatment options that are, in part, decided by prognostic survival. We developed the first machine-learning predictive algorithm specifically for MLS using the SEER registry that retained performance during external validation with institutional data.

Overcoming the radiosensitivity of chondrosarcoma (CS), the second most common primary bone tumor, is needed. Radioresistance is attributed to cancer stem cells (CSCs) in many malignancies. Disulfiram (DSF), an FDA-approved anti-alcoholism drug, complexed with Cu (DSF/Cu) can radiosensitize epithelial CSCs. This prompted us to investigate the radiosensitizing effect of DSF/Cu on CS CSCs (CCSCs). The radiosensitizing effects of DSF/Cu on CCSCs were investigated in vitro using cell lines SW1353 and CS-1. Stemness was identified independently by flow cytometry for CCSCs (ALDH+CD133+), sphere-forming ability, and Western blot analysis of stemness gene protein expression. The radiosensitizing effect of DSF/Cu was studied in an orthotopic CS xenograft mouse model by analyzing xenograft growth and residual xenografts for stemness. CCSCs were found to be resistant to single-dose (IR) and fractionated irradiation (FIR). IR and FIR increased CS stemness. Combined with DSF/Cu in vitro and in vivo, IR and FIR eliminated CS stemness. RT + DSF/Cu was safer and more effective than either RT ± DSF in inhibiting growth of orthotopic CS xenografts. In conclusion, DSF/Cu radiosensitizes CCSCs. These results can be translated into clinical trials for CS patients requiring RT for improved outcomes.

BACKGROUND CONTEXT Fungal spinal epidural abscess (FSEA) is a rare entity with high morbidity and mortality. Reports describing the clinical features, diagnosis, treatment, and outcomes of FSEA are scarce in the literature. PURPOSE This study aimed to describe the clinical features, diagnosis, treatment, and outcomes of FSEA. STUDY DESIGN This study is designed as a retrospective clinical case series. PATIENT SAMPLE A continuous series of patients with the diagnosis of FSEA who presented at our institution from 1993 to 2016. METHODS We reviewed the electronic medical records of patients with SEA who were treated within our hospital system from 1993 to 2016. We only included SEA cases that were due to fungi. We also reviewed FSEA cases in the English language literature from 1952 to 2017 to analyze the features of FSEA. RESULTS From a database of 1,053 SEA patients, we identified 9 patients with FSEA. Aspergillus fumigatus was isolated from 2 (22%) patients, and Candida species were isolated from 7 (78%). Focal spine pain, neurologic deficit, and fever were demonstrated in 89%, 50%, and 44% of FSEA cases, respectively. Five of nine cases involved the thoracic spine, and eight were located anterior to the thecal sac. Three cases had fungemia, six had long symptom duration (>2 weeks) prior to presentation, seven had concurrent immunosuppression, and eight had vertebral osteomyelitis. Additionally, one case had residual motor deficit at last follow-up, one had S1 sensory radicular symptoms, two suffered recurrent FSEA, two died within hospitalization, and two died within 90 days after discharge. CONCLUSIONS In summary, the classic diagnostic triad (focal spine pain, neurologic deficit, and fever) is not of great clinical utility for FSEA. Biopsy, intraoperative tissue culture, and blood culture can be used to diagnose FSEA. The most common pathogens of FSEA are Aspergillus and Candida species. Therefore, empiric treatment for FSEA should cover these species while definitive identification is pending. FSEA is found in patients with poor baseline health status, which is the essential reason for its high mortality.

None of the existing prognostic scoring systems for spinal epidural abscess (SEA) include albumin despite albumin's established role in inflammation, nutrition, lipid peroxidation, and regulation of apoptosis. The purpose of the present study was to determine the prognostic value of albumin in SEA.We performed a retrospective, case-control study of 2 independent data sets: patients with SEA in an institutional population and patients in the National Surgical Quality Improvement Program (NSQIP). Bivariate analyses and multivariate analyses were used to determine whether albumin is an independent prognostic factor for survival in both data sets.For the 1053 patients with SEA in the institutional cohort, the 90-day postdischarge mortality was 134 (12.7%). Overall, 633 (60.1%) underwent surgery in the initial admission, with a 30-day postoperative mortality rate of 5.5% (n = 35). For the 1154 patients with SEA in the NSQIP database, the 30-day postoperative mortality rate was 3.6% (n = 42). The rate of 90-day postdischarge mortality in the institutional cohort for patients with albumin2.3 g/dL was 25.1%. In contrast, the rate for patients with albumin3.3 g/dL was 4.5%. On multivariate analysis of the NSQIP database, hypoalbuminemia was an independent prognostic factor for 30-day postoperative mortality. On multivariate analysis of the institutional cohort, hypoalbuminemia remained a prognostic factor for 90-day postdischarge mortality.Albumin was validated as an independent prognostic factor in patients with SEA. The lack of this marker in existing scoring systems underscores the need for updated models to optimize risk stratification and shared decision-making before surgery.

Background Determination of the appropriateness of invasive management in patients with spinal metastatic disease requires accurate pre-operative estimation of survival. The purpose of this study was to examine serum alkaline phosphatase as a prognostic marker in spinal metastatic disease. Methods Chart reviews from two tertiary care centres were used to identify spinal metastatic disease patients. Bivariate and multivariate analyses were used to determine if serum alkaline phosphatase was an independent prognostic marker for survival. Results Overall, 732 patients were included with 90-day and 1-year survival of n = 539 (74.9%) and n = 324 (45.7%), respectively. The 1-year survival of patients in the first quartile of alkaline phosphatase (≤73 IU/L) was 78 (57.8%) compared to 31 (24.0%) for patients in the fourth quartile (>140 IU/L). Preoperative serum alkaline phosphatase levels were significantly elevated in patients with multiple spine metastases, non-spine bone metastasis, and visceral metastasis but not in patients with brain metastasis. On multivariate analysis, elevated serum alkaline phosphatase was identified as an independent prognostic factor for survival in spinal metastatic disease. Conclusion Serum alkaline phosphatase is associated with preoperative metastatic tumour burden and is a biomarker for overall survival in spinal metastatic disease.

Dedifferentiated chordoma is a rare chordoma subtype characterized by a high-grade sarcoma juxtaposed to conventional chordoma. We identified a series of dedifferentiated chordomas, reviewed clinicopathologic features, performed next-generation sequencing in select cases, and analyzed all related English-language publications. Our series included 7 men and 3 women (age 15 to 80 y [median: 54 y];1% of1000 chordomas surveyed). The tumor (2.8 to 24.5 cm [median: 5.8 cm] in size) presented de novo or as recurrence (including postradiotherapy) in sacrum (n=5), skull base (n=2), lumbar spine (n=1), thoracic/mediastinum (n=1), and lung (n=1; as metastasis). Histologically, the dedifferentiated component (3% to 95% [median: 60%]) was pleomorphic-to-fibrosarcomatous, juxtaposed to conventional (n=8) or chondroid (n=2) component. By immunohistochemistry, the conventional/chondroid component consistently expressed cytokeratin and brachyury, whereas the dedifferentiated component showed loss of both. We identified a sacral conventional chordoma with INI1 loss, with one of the lung metastases showing biphasic histology with loss of cytokeratin and brachyury in the dedifferentiated component. Sequencing identified tumor suppressor mutations in 4 tumors, including TP53 mutations in the dedifferentiated component in 3 tumors. Of 7 patients with follow-up, 6 developed metastases; 4 died at 15 to 99 months (median: 24 mo) after dedifferentiated chordoma diagnosis. Collectively, of 87 dedifferentiated chordoma patients described in 1913-2020 (including 10 herein), the median overall survival was 20 months. In summary, dedifferentiated chordoma involves diverse sites and presents de novo, postradiotherapy, or as recurrence/metastasis months-to-years after initial diagnosis. The dedifferentiated component shows loss of brachyury and cytokeratin staining and harbors recurrent TP53 mutations, implicating tumor suppressor dysregulation in chordoma dedifferentiation.

BACKGROUND: The Skeletal Oncology Research Group (SORG) machine learning algorithm for predicting survival in patients with chondrosarcoma was developed using data from the Surveillance, Epidemiology, and End Results (SEER) registry. This algorithm was externally validated on a dataset of patients from the United States in an earlier study, where it demonstrated generally good performance but overestimated 5-year survival. In addition, this algorithm has not yet been validated in patients outside the United States; doing so would be important because external validation is necessary as algorithm performance may be misleading when applied in different populations. QUESTIONS/PURPOSES: Does the SORG algorithm retain validity in patients who underwent surgery for primary chondrosarcoma outside the United States, specifically in Italy? METHODS: A total of 737 patients were treated for chondrosarcoma between January 2000 and October 2014 at the Italian tertiary care center which was used for international validation. We excluded patients whose first surgical procedure was performed elsewhere (n = 25), patients who underwent nonsurgical treatment (n = 27), patients with a chondrosarcoma of the soft tissue or skull (n = 60), and patients with peripheral, periosteal, or mesenchymal chondrosarcoma (n = 161). Thus, 464 patients were ultimately included in this external validation study, as the earlier performed SEER study was used as the training set. Therefore, this study-unlike most of this type-does not have a training and validation set. Although the earlier study overestimated 5-year survival, we did not modify the algorithm in this report, as this is the first international validation and the prior performance in the single-institution validation study from the United States may have been driven by a small sample or non-generalizable patterns related to its single-center setting. Variables needed for the SORG algorithm were manually collected from electronic medical records. These included sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location. By inputting these variables into the algorithm, we calculated the predicted probabilities of survival for each patient. The performance of the SORG algorithm was assessed in this study through discrimination (the ability of a model to distinguish between a binary outcome), calibration (the agreement of observed and predicted outcomes), overall performance (the accuracy of predictions), and decision curve analysis (establishment on the ability of a model to make a decision better than without using the model). For discrimination, the c-statistic (commonly known as the area under the receiver operating characteristic curve for binary classification) was calculated; this ranged from 0.5 (no better than chance) to 1.0 (excellent discrimination). The agreement between predicted and observed outcomes was visualized with a calibration plot, and the calibration slope and intercept were calculated. Perfect calibration results in a slope of 1 and an intercept of 0. For overall performance, the Brier score and the null-model Brier score were calculated. The Brier score ranges from 0 (perfect prediction) to 1 (poorest prediction). Appropriate interpretation of the Brier score requires comparison with the null-model Brier score. The null-model Brier score is the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for every patient. A decision curve analysis was performed to compare the potential net benefit of the algorithm versus other means of decision support, such as treating all or none of the patients. There were several differences between this study and the earlier SEER study, and such differences are important because they help us to determine the performance of the algorithm in a group different from the initial study population. In this study from Italy, 5-year survival was different from the earlier SEER study (71% [319 of 450 patients] versus 76% [1131 of 1487 patients]; p = 0.03). There were more patients with dedifferentiated chondrosarcoma than in the earlier SEER study (25% [118 of 464 patients] versus 8.5% [131 of 1544 patients]; p < 0.001). In addition, in this study patients were older, tumor size was larger, and there were higher proportions of high-grade tumors than the earlier SEER study (age: 56 years [interquartile range {IQR} 42 to 67] versus 52 years [IQR 40 to 64]; p = 0.007; tumor size: 80 mm [IQR 50 to 120] versus 70 mm [IQR 42 to 105]; p < 0.001; tumor grade: 22% [104 of 464 had Grade 1], 42% [196 of 464 had Grade 2], and 35% [164 of 464 had Grade 3] versus 41% [592 of 1456 had Grade 1], 40% [588 of 1456 had Grade 2], and 19% [276 of 1456 had Grade 3]; p ≤ 0.001). RESULTS: Validation of the SORG algorithm in a primarily Italian population achieved a c-statistic of 0.86 (95% confidence interval 0.82 to 0.89), suggesting good-to-excellent discrimination. The calibration plot showed good agreement between the predicted probability and observed survival in the probability thresholds of 0.8 to 1.0. With predicted survival probabilities lower than 0.8, however, the SORG algorithm underestimated the observed proportion of patients with 5-year survival, reflected in the overall calibration intercept of 0.82 (95% CI 0.67 to 0.98) and calibration slope of 0.68 (95% CI 0.42 to 0.95). The Brier score for 5-year survival was 0.15, compared with a null-model Brier of 0.21. The algorithm showed a favorable decision curve analysis in the validation cohort. CONCLUSIONS: The SORG algorithm to predict 5-year survival for patients with chondrosarcoma held good discriminative ability and overall performance on international external validation; however, it underestimated 5-year survival for patients with predicted probabilities from 0 to 0.8 because the calibration plot was not perfectly aligned for the observed outcomes, which resulted in a maximum underestimation of 20%. The differences may reflect the baseline differences noted between the two study populations. The overall performance of the algorithm supports the utility of the algorithm and validation presented here. The freely available digital application for the algorithm is available here: https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE: Level III, prognostic study.

Background Preoperative prognostication of short-term postoperative mortality in patients with spinal metastatic disease can improve shared decision making around end-of-life care. Objective To (1) develop machine learning algorithms for prediction of short-term mortality and (2) deploy these models in an open access web application. Methods The American College of Surgeons, National Surgical Quality Improvement Program was used to identify patients that underwent operative intervention for metastatic disease. Four machine learning algorithms were developed, and the algorithm with the best performance across discrimination, calibration, and overall performance was integrated into an open access web application. Results The 30-d mortality for the 1790 patients undergoing surgery for spinal metastatic disease was 8.49%. Preoperative factors used for prognostication were albumin, functional status, white blood cell count, hematocrit, alkaline phosphatase, spinal location (cervical, thoracic, lumbosacral), and severity of comorbid systemic disease (American Society of Anesthesiologist Class). In this population, machine learning algorithms developed to predict 30-d mortality performed well on discrimination (c-statistic), calibration (assessed by calibration slope and intercept), Brier score, and decision analysis. An open access web application was developed for the best performing model and this web application can be found here: https://sorg-apps.shinyapps.io/spinemets/. Conclusion Machine learning algorithms are promising for prediction of postoperative outcomes in spinal oncology and these algorithms can be integrated into clinically useful decision tools. As the volume of data in oncology continues to grow, creation of learning systems and deployment of these systems as accessible tools may significantly enhance prognostication and management.

Background Context: Postoperative morbidity may offset the potential benefits of surgical treatment for spine metastatic disease; hence, risk factors for postoperative complications and reoperations should be taken into considerations during surgical decision-making. In addition, it remains unknown whether complications and reoperations shorten these patients’ survival. Purpose: We aimed to describe and identify factors associated with having a complication within 30 days of index surgery as well as factors associated with having a subsequent reoperation. Furthermore, we assessed the effect of 30-day complications and reoperations on the patients’ postoperative survival, as well as described neurologic changes after surgery. Study Design: Retrospective cohort study. Patient Sample: We included 647 patients 18 years and older who had surgery for metastatic disease in the spine between January 2002 and January 2014 in one of two affiliated tertiary care centers. Outcome Measures: Our primary outcomes were complications within 30 days after surgery and reoperations until final follow-up or death. Methods: We used multivariate logistic regression to identify risk factors for 30-day complications and reoperations. We used the Cox regression analysis to assess the effect of postoperative complications and reoperations on survival. Results: From 647 included patients, 205 (32%) had a complication within 30 days. The following variables were independently associated with 30-day complications: lower albumin levels (odds ratio [OR]: 0.69, 95% confidence interval [CI]=0.49–0.96, p=.021), additional comorbidities (OR=1.42, 95% CI=1.00–2.01, p=.048), pathologic fracture (OR=1.41, 95% CI=0.97–2.05, p=.031), three or more spine levels operated upon (OR=1.64, 95% CI=1.02–2.64, p=.027), and combined surgical approach (OR=2.44, 95% CI=1.06–5.60, p=.036). One hundred and fifteen patients (18%) had at least one reoperation after the initial surgery; prior radiotherapy (OR=1.56, 95% CI=1.07–2.29, p=.021) to the spinal tumor was independently associated with reoperation. 30-day complications were associated with worse survival (hazard ratio [HR]=1.40, 95% CI=1.17–1.68, p

Purpose Chordomas are malignant tumors arising from remnant notochordal tissue. Despite improved local control with preoperative/postoperative radiation therapy (RT), progression-free survival and overall survival (OS) remain poor in patients with high-risk features. Chordoma has been identified to express and activate platelet-derived growth factor receptor signaling. We conducted a phase 1 trial to identify the maximum tolerated dose (MTD), safety, and feasibility of nilotinib with RT as either preoperative or definitive treatment for patients with high-risk chordoma. Methods and Materials We recruited 23 patients with high-risk, nonmetastatic chordoma. High risk was defined as the presence of any of the following: local recurrence after surgery, previous intralesional resection, unplanned incomplete resection, unresectable or marginally resectable disease based on locally advanced stage, or declining surgery because of excessive morbidity. Patients were treated with nilotinib and concurrent RT to 50.4 Gy relative biological effectiveness (RBE) followed by surgery and postoperative RT to a cumulative dose up to 70.2 Gy RBE or definitively up to 77.4 Gy RBE without surgery. On completion of RT, patients were eligible to continue nilotinib until disease progression. Results In patients receiving nilotinib 200 mg twice daily with RT, 3 dose-limiting toxicities (DLT) occurred in 5 patients. One DLT was seen among 6 patients receiving nilotinib 200 mg daily with RT. Therefore, 200 mg daily was declared the maximum tolerated dose. Eleven additional patients received nilotinib with RT at the maximum tolerated dose, and 1 additional DLT occurred. The objective best response rate was 6% (1 of 18 patients, 95% confidence interval [CI], 0.1%-27%). The median progression-free survival was 58.15 months (95% CI, 39.10-∞). The median OS was 61.5 months (43.1-∞), and the 2-year OS rate was 95%. Conclusions Nilotinib 200 mg/d with RT is safe and tolerated in patients with high-risk chordoma. Long-term follow-up is needed to understand whether nilotinib combined with RT, with or without surgery, adds greater improvement to progression-free survival or OS than with RT with or without surgery alone in patients with high-risk chordoma.

Background Chordomas are locally invasive slow-growing tumors that are difficult to study because of the rarity of the tumors and the lack of significant volumes of patients with longitudinal follow-up. As such, there are currently no machine learning studies in the chordoma literature. The purpose of this study was to develop machine learning models for survival prediction and deploy them as open access web applications as a proof of concept for machine learning in rare nervous system lesions. Methods The National Cancer Institute's Surveillance, Epidemiology, and End Results program database was used to identify adult patients diagnosed with spinal chordoma between 1995 and 2010. Four machine learning models were used to predict 5-year survival for spinal chordoma and assessed by discrimination, calibration, and overall performance. Results The 5-year overall survival for 265 patients with spinal chordoma was 67.5%. Variables used for prediction were age at diagnosis, tumor size, tumor location, extent of tumor invasion, and extent of surgery. For 5-year survival prediction, the Bayes Point Machine achieved the best performance with a c statistic of 0.80, calibration slope of 1.01, calibration intercept of 0.03, and Brier score of 0.16. This model for 5-year mortality prediction was incorporated into an open access application and can be found online ( https://sorg-apps.shinyapps.io/chordoma/ ). Conclusions This analysis of patients with spinal chordoma demonstrated that machine learning models can be developed for survival prediction in rare pathologies and have the potential to serve as the basis for creation of decision support tools in the future.

Background Context Despite advances in spinal oncology, research in patient-based prognostic calculators for metastatic spine disease is lacking. Much of the literature in this area investigates the general predictive accuracy of scoring systems in heterogeneous populations, with few studies considering the accuracy of scoring systems based on patient specifics such as type of primary tumor. Purpose The aim of the present study was to compare the ability of widespread scoring systems to estimate both overall survival at various time points and tumor-specific survival for patients undergoing surgical treatment for metastatic spine disease in order to provide surgeons with information to determine the most appropriate scoring system for a specific patient and timeline. Study Design This is a retrospective study. Patient Sample Patients who underwent surgical resection for metastatic spine disease at a single institution were included. Outcome Measures Areas under the receiver operating characteristic curves were generated from comparison of actual survival of patients and survival as predicted by application of prevalent scoring systems. Methods A preoperative score for all 176 patients was retrospectively calculated utilizing the Skeletal Oncology Research Group (SORG) Classic Scoring Algorithm, SORG Nomogram, original Tokuhashi, revised Tokuhashi, Tomita, original Bauer, modified Bauer, Katagiri, and van der Linden scoring systems. Univariate and multivariate Cox proportional hazard models were constructed to assess the association of patient variables with survival. Receiver operating characteristic analysis modeling was utilized to quantify the accuracy of each test at different end points and for different primary tumor subgroups. No funds were received in support of this work. The authors have no conflicts of interest to disclose. Results Among all patients surgically treated for metastatic spine disease, the SORG Nomogram demonstrated the highest accuracy at predicting 30-day (area under the curve [AUC] 0.81) and 90-day (AUC 0.70) survival after surgery. The original Tokuhashi was the most accurate at predicting 365-day survival (AUC 0.78). Multivariate analysis demonstrated multiple preoperative factors strongly associated with survival after surgery for spinal metastasis. The accuracy of each scoring system in determining survival probability relative to primary tumor etiology and time elapsed since surgery was assessed. Conclusions Among the nine scoring systems assessed, the present study determined the most accurate scoring system for short-term (30-day), intermediate (90-day), and long-term (365-day) survival, relative to primary tumor etiology. The findings of the present study may be utilized by surgeons in a personalized effort to select the most appropriate scoring system for a given patient.

Background Previous studies have shown that venous thromboembolism (VTE) is a complication associated with neoplastic disease and major orthopaedic surgery. However, many potential risk factors remain undefined. Questions/purposes (1) What proportion of patients develop symptomatic VTE after surgery for long bone metastases? (2) What factors are associated with the development of symptomatic VTE among patients receiving surgery for long bone metastases? (3) Is there an association between the development of symptomatic VTE and 1-year survival among patients undergoing surgery for long bone metastases? (4) Does chemoprophylaxis increase the risk of wound complications among patients undergoing surgery for long bone metastases? Methods A retrospective study identified 682 patients undergoing surgical treatment of long bone metastases between 2002 and 2013 at the Massachusetts General Hospital and Brigham and Women's Hospital. We included patients 18 years of age or older who had a surgical procedure for impending or pathologic metastatic long bone fracture. We considered the humerus, radius, ulna, femur, tibia, and fibula as long bones; metastatic disease was defined as metastases from solid organs, multiple myeloma, or lymphoma. In general, we used 40 mg enoxaparin daily for lower extremity surgery and 325 mg aspirin daily for lower or upper extremity surgery. The primary outcome was a VTE defined as any symptomatic pulmonary embolism (PE) or symptomatic deep vein thrombosis (DVT; proximal and distal) within 90 days of surgery as determined by chart review. The tertiary outcome was defined as any documented wound complication that might be attributable to chemoprophylaxis within 90 days of surgery. At followup after 90 days and 1 year, respectively, 4% (25 of 682) and 8% (53 of 682) were lost to followup. Statistical analysis was performed using multivariable logistic and Cox regression and Kaplan-Meier. Results Overall, 6% (44 of 682) of patients had symptomatic VTE; 22 patients sustained a DVT, and 22 developed a PE. After controlling for relevant confounding variables, higher preoperative hemoglobin level was independently associated (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.60-0.93; p = 0.011) with decreased symptomatic VTE risk, the presence of symptomatic VTE was associated with a worse 1-year survival rate (VTE: 27% [95% CI, 14%-40%] and non-VTE: 39% [95% CI, 35%-43%]; p = 0.041), and no association was found between wound complications and the use of chemoprophylaxis (OR, 3.29; 95% CI, 0.43-25.17; p = 0.252). Conclusions The risk of symptomatic 90-day VTE is high in patients undergoing surgery for long bone metastases. Further study would be needed to determine the VTE prevention strategy that best balances risks and benefits to address this complication. Level of evidence Level III, therapeutic study.

Chordoma is a rare malignant tumor of bone with high morbidity and mortality. Recently, aggressive pediatric poorly differentiated chordoma with SMARCB1 loss has been described. This study summarizes the clinicopathologic features of poorly differentiated chordoma with SMARCB1 loss in the largest series to date. A search of records between 1990-2017 at MGH identified 19 patients with poorly differentiated chordoma. Immunohistochemical stains were evaluated. Kaplan-Meier survival statistics and log-rank (Mantel Cox) tests compared survival with other subtypes. The patients (n = 19) were diagnosed at a median age of 11 years (range: 1-29). Tumors arose in the skull base and clivus (n = 10/19; 53%); cervical spine (n = 6/19; 32%); and sacrum or coccyx (n = 3/19; 16%). The clinical stage of these patients (AJCC 7e) was stage 2A (n = 7/16; 44%); stage 2B (n = 6/16; 38%); stage 4A (n = 1/16; 6%); and stage 4B (n = 2/16; 13%). The tumors were composed of sheets of epithelioid cells with nuclear pleomorphism, abundant eosinophilic cytoplasm, and increased mitoses. Tumors were positive for cytokeratin (n = 18/18; 100%) and brachyury (n = 18/18; 100%). Patients were treated with a combination of excision, radiation therapy, and chemotherapy. No difference in overall survival, progression free survival, local control time, and metastasis free survival was identified between poorly differentiated chordoma of the skull base and of the spine. Compared to other chordoma subtypes, poorly differentiated chordoma has a significantly decreased mean overall survival after stratification by site (p = 0.037). Pediatric poorly differentiated chordoma has a distinct clinical and immunohistochemical profile, with characteristic SMARCB1 loss and decreased survival compared to conventional/chondroid chordoma. Recognition of this subtype is important because these malignancies should be treated aggressively with multimodality therapy.

Background Spinal epidural abscess is a high-risk condition that can lead to paralysis or death. It would be of clinical and prognostic utility to identify which subset of patients with spinal epidural abscess is likely to develop a motor deficit or die within 90 days of discharge. Methods We identified all patients ≥18 years of age who were admitted to our hospital system with a diagnosis of spinal epidural abscess during the period of 1993 to 2016. Explanatory variables were collected retrospectively. Bivariate and multivariable logistic regression was performed using these variables to identify independent predictors of motor deficit and 90-day mortality. Nomograms were then constructed to quantify the risk of these outcomes. Results Of the 1,053 patients we identified with spinal epidural abscess, 362 presented with motor weakness. One hundred and thirty-four patients died within 90 days of discharge, inclusive of those who died during hospitalization. Multivariable logistic regression yielded 8 independent predictors of pre-treatment motor deficit and 8 independent predictors of 90-day mortality. We constructed nomograms that generated a probability of pre-treatment motor deficit or 90-day mortality on the basis of the presence of these factors. Conclusions By quantifying the risk of pre-treatment motor deficit and 90-day mortality, our nomograms may provide useful prognostic information for the treatment team. Timely treatment of neurologically intact patients with a high risk of developing a motor deficit is necessary to avoid residual motor weakness and improve survival. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of Levels of Evidence.

STUDY DESIGN This was a retrospective cohort study from 2 affiliated tertiary care referral centers for spine disease. OBJECTIVE The purpose of this article was to assess the prevalence of incidental (ie, asymptomatic) and symptomatic lumbar synovial facet cysts on magnetic resonance imaging. Secondarily, we assessed whether the prevalence increases with age. In addition, we assessed differences in patient and cyst characteristics between asymptomatic and symptomatic facet cysts. SUMMARY OF BACKGROUND The prevalence of symptomatic and asymptomatic synovial facet cysts in the lumbar spine has been incompletely established, and, although many studies demonstrate an association with degenerative spine disease, no cumulative increase in prevalence of synovial facet cysts with increasing age has been presented. METHODS We included 19,010 consecutive patients who underwent a dedicated lumbar spine magnetic resonance imaging between 2004 and 2015. Our outcome measures were symptomatic and asymptomatic facet cysts. A symptomatic cyst was defined as a cyst with symptoms of radiculopathy on the same side as the cyst. RESULTS The overall synovial facet cyst prevalence was 6.5% [95% confidence interval (CI), 6.1-6.8]; 46% of the facet cysts were incidental and 54% were symptomatic. Increased age was independently associated with a higher likelihood of having a synovial facet cyst [odds ratio (per 10 y), 1.24, 95% CI, 1.20-1.29; P

Prompt diagnosis and treatment are critical in spinal epidural abscess, as delay can lead to paralysis or death. The initial management decision for spinal epidural abscess is not always clear, with the literature showing conflicting results. When considering nonoperative management, it is crucial to avoid failure of treatment, given the neurologic compromise incurred through failure. Unfortunately, data regarding risk factors associated with failure are scarce.All patients admitted to our hospital system with a diagnosis of spinal epidural abscess from 1993 to 2016 were identified. Patients who were ≥18 years of age and were initially managed nonoperatively were included. Explanatory variables and outcomes were collected retrospectively. Bivariate and multivariable analyses were performed on these variables to identify independent predictors of failure of nonoperative treatment. A nomogram was constructed to generate a risk of failure based on these predictors.We identified 367 patients who initially underwent nonoperative management. Of these, 99 patients underwent medical management that failed. Multivariable logistic regression yielded 6 independent predictors of failure: a presenting motor deficit, pathologic or compression fracture in affected levels, active malignancy, diabetes mellitus, sensory changes, and dorsal location of abscess. We constructed a nomogram that generates a probability of failure based on the presence of these factors.By quantifying the risk of failure on the basis of the presence of 6 independent predictors of treatment failure, our nomogram may provide a useful tool for the treatment team when weighing the risks and benefits of initial nonoperative treatment compared with operative management.Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background We assessed whether there was a difference in attenuation measurements (in Hounsfield units – HU) and geometric distribution of HU between femora with metastatic lesions that fracture, and metastatic lesions that did not fracture nor underwent prophylactic fixation. Methods Nine patients with femoral metastases who underwent CT and developed a pathological fracture were matched to controls. All femora were delineated in axial CT slices using a region of interest (ROI) tool; the HU within these ROIs were used to calculate: (1) the cumulative HU of the affected over the nonaffected side per slice and presented as a percentage, and (2) the cumulative HU accounting for geometric distribution (polar moment of HU). We repeated the analyses including cortical bone only (HU of 600 and above). Results CT-based calculations did not differ between patients with a lesion that fractured and those that did not fracture nor underwent prophylactic fixation when analyzing all tissue. However, when including cortical bone only, the pathological fracture group had a lower cumulative HU value compared to the no fracture and no fixation group for the weakest cross-sectional CT image (pathological fracture group, mean: 71, SD: 23 and no fracture and no prophylactic fixation group, mean: 85, SD: 18, p = 0.042) and the complete lesion analysis (pathological fracture group, mean: 78, SD: 21 and no fracture and no prophylactic fixation group, mean: 92, SD: 15, p = 0.032). Conclusion The demonstrated CT-based algorithms can be useful for predicting pathological fractures in metastatic lesions.

Hypothesis: This study assessed, if there was a difference in surgical decision making for metastatic humeral lesions based on; orthopaedic subspecialty, tumor characteristics.Study type: Cross sectional survey study.Materials and methods: Twenty-four case scenarios were created by combining: tumor type, life expectancy, fracture type, and anatomical location. Participants were asked for every case: what treatment would you recommend? Participants were 78 (48%) orthopaedic oncologists and 83 (52%) orthopaedic surgeons that were not regularly involved in the treatment of bone tumors.Results: There was a difference between orthopaedic oncologists and other subspecialty surgeons in recommendation for specific treatments: intramedullary nailing was less often recommended by orthopaedic oncologists (53%, 95%CI: 47-59) compared to other surgeons (62%, 95%CI: 57-67) (p = 0.023); while endoprosthetic reconstruction (orthopaedic oncologists: 8.8% [95%CI: 6.6-11], other surgeons: 3.6%[95%CI: 2.3-4.8], p Discussion: Subspecialty training and patient and tumor characteristics influence the decision for operative management and the decision for a specific implant in metastatic humeral fractures. (C) 2017 Elsevier Masson SAS. All rights reserved.

Background: Elevated serum alkaline phosphatase has been previously studied as a biomarker for progression of metastatic disease and implicated in adverse skeletal events and worsened survival. The purpose of this study was to determine if serum alkaline phosphatase was a predictor of short-term mortality of patients undergoing surgery for spinal metastatic disease. Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried for patients undergoing spinal surgery for metastatic disease. Bivariate and multivariable analyses was undertaken to determine the relationship between serum alkaline phosphatase and 30-day mortality. Results: For the 1788 patients undergoing operative intervention for spinal metastatic disease between 2009 and 2016 the 30-day mortality was 8.49% (n = 151). In patients who survived beyond 30-days after surgery, n = 1627 (91.5%) the median [interquartile range] serum alkaline phosphatase levels were 126.4 [75–138], whereas in patients who had 30-day mortality, the serum alkaline phosphatase levels were 179.8 [114–187]. The optimal cut-off for alkaline phosphatase was determined to be 113 IU/L. On multivariable analysis, elevated serum alkaline phosphatase levels were associated with 30-day mortality (OR 1.61, 95% CI 1.12–2.32, p = 0.011). Conclusion: Elevated preoperative serum alkaline phosphatase is a marker for 30-day mortality in patients undergoing surgery for spinal metastatic disease. Future retrospective and prospective study designs should incorporate assessment of this serum biomarker to better understand the role for serum alkaline phosphatase in improving prognostication in spinal metastatic disease.

Venous thromboembolism (VTE) is known to be independently associated with both orthopaedic surgery and malignancy. Patients undergoing surgery for musculoskeletal malignancies are at an increased risk for thromboembolic events. Although VTE can lead to serious morbidity and mortality, the potential complications of prophylactic anticoagulation call for a greater understanding of a patient's risk factors, as well as more rigorous guidelines for prophylactic anticoagulation regimens. The aims of this study were to 1) Analyze the rate of VTE in patients surgically treated for primary bone sarcoma; 2) Identify risk factors for VTE in patients with primary bone sarcoma; 3) Discuss the complications associated with prophylactic anticoagulation in patients with primary bone sarcoma. Methods This retrospective study identified all patients 18 years and older treated surgically at our institution for a primary bone sarcoma between 1990 and 2015. All patients with at least 90 days of post-operative follow-up from the index surgery were analyzed for occurrence of VTE. Those with an event were compared to those without to identify predictors of VTE. Results 21 patients (5.5%) had a clinically symptomatic, radiographically confirmed VTE within 90 days of index surgery (12 DVT, 9 PE). Higher preoperative white blood cell count (OR 1.15, 95% CI 1.01–1.29) and post-operative wound complications (OR 5.01, 95% CI 1.93–13.55) were found to be independent risk factors for VTE. No differences in terms of efficacy were found among medications. The risk of wound complications increased significantly in patients who received chemical prophylaxis (OR 2.21, 95% CI 1.00–4.87). Conclusions Our patient population had a relatively low rate of VTE as compared to the literature. Preoperative white blood cell count (WBC) and post-operative wound complications were both found to be independently associated predictors for VTE in patients with primary bone sarcoma. An elevated WBC may reflect hemoconcentration which per se is prothrombotic in nature. Aggressive DVT prophylaxis may, counter intuitively, increase the risk of thromboembolic events due to prolonged immobilization and additional surgeries that usually occur when addressing postoperative wound complications such as postoperative hematoma and wound dehiscence that may relate to overanticoagulation. Prospective randomized trials comparing different medications in combination with compressive devices are needed to assess efficacy with the lowest complication profile. Simpler protocols may increase patient compliance to prophylactic treatment.

This is a retrospective study.To compare (1) recurrence of radiculopathy and (2) back pain after decompression with and without fusion for patients with a symptomatic synovial cyst.Previous work described favorable outcomes following cyst excision with and without fusion. Because of the association of facet cysts with spinal instability it is hypothesized that a decompression with fusion will lead to better outcomes. However, previous studies present contradicting results.We included 314 consecutive patients that underwent operative treatment for a facet cyst between 2003 and 2013 at 2 tertiary spine referral centers: 224 (71%) underwent decompression without fusion (35% spondylolisthesis), 90 (29%) underwent decompression with fusion (63% spondylolisthesis). Baseline data were compared between the groups. Bivariate log-rank analysis was used to compare outcomes between groups, followed by multivariable Cox regression analysis accounting for differences in baseline characteristics.Patients undergoing decompression with fusion presented with a higher incidence of back pain (P=0.004) and spondylolisthesis (P0.001), had more often bilateral decompressions (P0.001), more facetectomies (P0.001), and more levels of decompression (P=0.004) than those who underwent decompression alone. We found a difference in recurrence of radiculopathy (no fusion: 25% vs. fusion: 9.4%, P=0.029) in bivariate analysis. However, this difference did not hold when accounting for confounders (hazard ratio, 0.50, 95% confidence interval, 0.19-1.31, P=0.16). There was no difference in recurrence of back pain in bivariate (no fusion: 29% vs. fusion: 22%, P=0.51) and multivariable analysis (hazard ratio 0.51, 95% confidence interval, 0.23-1.14, P=0.10).We found, with the numbers evaluated, no difference in recurrence of radiculopathy or back pain between patients undergoing decompression with or without fusion after accounting for confounders. The decision for fusion should be considered in light of the extent of decompression and the existence of other pathology.Level III-therapeutic study.

This case reports a 25-year-old woman initially diagnosed with adjacent benign notochordal cell tumors (BNCTs) of L3 and L4 based on needle biopsy of L3 and stable imaging over a 3-year period who was ultimately found to have a chordoma arising from a BNCT at L3. It illustrates the potential relationship between benign and malignant notochordal tumors and the difficulty in distinguishing them by clinical, radiological, and even histopathological means.

Spinal epidural lipomatosis (SEL) refers to an excessive accumulation of fat within the epidural space. It can be idiopathic or secondary, resulting in significant morbidity. The prevalence of SEL, including idiopathic and secondary SEL, and its respective risk factors are poorly defined.We sought to: (1) assess the prevalence of SEL among patients who underwent a dedicated magnetic resonance imaging (MRI) scan of the spine-including incidental SEL (ie, SEL without any spine-related symptoms), SEL with spine-related symptoms, and symptomatic SEL (ie, with symptoms specific for SEL); and (2) assess factors associated with overall SEL and subgroups. In addition, we assessed differences between SEL subgroups.We reviewed the records of 28,902 patients, aged 18 years and older with a spine MRI (2004 to 2015) at two tertiary care centers. We identified SEL cases by searching radiology reports for SEL, including synonyms and misspellings. Prevalence numbers were calculated as a percentage of the total number of patients. We used multivariate logistic regression analysis to identify factors associated with overall SEL and subgroups.The prevalence of overall SEL was 2.5% (731 of 28,902): incidental SEL, 0.6% (168 of 28,902); SEL with symptoms, 1.8% (526 of 28,902); and symptomatic SEL, 0.1% (37 of 28,902). Factors associated with overall SEL in multivariate analysis were the following: older age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 1.01-1.02, p.001), higher modified Charlson comorbidity index (OR: 1.10, 95% CI: 1.07-1.13, p.001), male sex (OR: 2.01, 95% CI: 1.71-2.37, p.001), BMI30 (OR: 2.59, 95% CI: 1.97-3.41, p.001), Black/African American race (OR: 1.66, 95% CI: 1.24-2.23, p=.001), systemic corticosteroid use (OR: 2.59, 95% CI: 1.69-3.99, p.001), and epidural corticosteroid injections (OR: 3.48, 95% CI: 2.82-4.30, p.001).We found that about 1 in 40 patients undergoing a spine MRI had SEL; 23% of whom with no symptoms, 72% with spine-related symptoms, and 5% with symptoms specific for SEL. Our data help identify patients who might warrant an increased index of suspicion for SEL.

To describe the population and functional changes observed after an inpatient rehabilitation facility stay in chordoma patients Materials and Methods: We conducted a consecutive series retrospective review of patients with chordoma, admitted to an academic inpatient rehabilitation facility after surgical resection from 2010 to 2015. Information regarding demographic, tumor- and surgery-specific data, lengths of stay, complications, admission and discharge functional independence measure scores was collected.A total of 40 patients with a diagnosis of chordoma were admitted to an inpatient rehabilitation facility postoperatively were included for analysis. Thirty-three patients had initial resection of chordoma, seven patients had resection of recurrent chordoma, and eight patients had metastatic disease on admission to an inpatient rehabilitation facility. The average change in total and motor functional independence measure scores after an inpatient rehabilitation facility stay was 33.7 and 26.1, respectively. The acute hospital transfer rate was 32.5% and the postoperative complication rate was 62.5%.This study is the first to describe the population and functional improvement in the chordoma population who are admitted to an inpatient rehabilitation facility postoperatively. While there is a high rate of acute hospital transfer and postoperative complications, these values are comparable to prior studies in this population. With the increasing prevalence of cancer survivors, improving function during and after cancer treatment is extremely important. Implications for Rehabilitation Chordoma patients who are admitted to inpatient rehabilitation facilities after surgical tumor resection experience improvement in multiple functional domains. Chordoma patients admitted to inpatient rehabilitation facilities experience a high rate of acute hospital transfer, but it is comparable to other cancer rehabilitation populations. Understanding the characteristics of the postoperative chordoma population is essential to direct future studies regarding cancer rehabilitation.

Background The main reconstruction techniques for proximal humerus tumors include osteoarticular allografts (OAs), endoprostheses (EPs), or allograft prosthetic composites (APCs). A common complication is infection, and constructs involving the use of allografts are believed to be at a higher risk of infection. Literature comparing infection rates between different modalities of reconstruction is scarce and underpowered. The study purposes were (1) to determine and compare the prevalence of infection in patients who underwent reconstruction of the proximal humerus including OAs, EPs, and APCs; (2) to identify preoperative, perioperative, and postoperative predictors of infection that might be modifiable; and (3) to present our protocol of treatment in patients with superficial and deep infections. Methods We reviewed 150 patients of all ages with proximal humerus tumors treated by an OA, EP, or APC at 2 tertiary institutions. The prevalence of infection for each modality was calculated and compared between groups. We identified potential predictors of infection with stepwise backward multivariate Cox regression analysis. Results An infection developed in 19 patients (12%): 5 of 45 (11%) in the OA group, 12 of 85 (14%) in the EP group, and 2 of 20 (10%) in the APC group ( P = .740). A lower preoperative hemoglobin blood level and low preoperative albumin blood level were independently associated with infection. Conclusions We found similar infection rates compared with previously reported series. However, we did not identify a higher infection prevalence in constructs using allografts. Patients with a lower preoperative hemoglobin or albumin level are at higher risk of infection and should undergo optimization before surgery.

General questionnaires are often used to assess quality of life in patients with spine metastases, although a disease-specific survey did not exist until recently. The Spine Oncology Study Group has developed an outcomes questionnaire (SOSG-OQ) to measure quality of life in these patients. However, a scoring system was not developed, and the questionnaire was not validated in a group of patients, nor was it compared with other general quality of life questionnaires such as the EuroQol 5 Dimensions (EQ-5D) questionnaire.Our primary null hypothesis is that there is no association between the SOSG-OQ and EQ-5D. Our secondary null hypothesis is that there is no difference in coverage and internal consistency between the SOSG-OQ and EQ-5D. We also assess coverage, consistency, and validity of the domains within the SOSG-OQ.A survey study from a tertiary care spine referral center was used for this study.The patient sample consisted of 82 patients with spine metastases, myeloma, or lymphoma.The SOSG-OQ (27 questions, 6 domains) score ranges from 0 to 80, with a higher score indicating worse quality of life. The EQ-5D (5 questions, 5 domains) index score ranges from 0 to 1, with a higher score indicating better quality of life.The association between the SOSG-OQ and EQ-5D index score was assessed using the Spearman rank correlation. Instrument coverage and precision were assessed by determining item completion rate, median score with range, and floor and ceiling effect. Internal consistency was assessed using Cronbach alpha. Multitrait analysis and exploratory factor analysis were used to analyze properties of the individual domains in the SOSG-OQ.The Spearman rank correlation between the SOSG-OQ and EQ-5D questionnaire was high (r=-0.83, p.001). Internal consistency of the SOSG-OQ (0.92, 95% CI: 0.89-0.94) was higher as compared to the internal consistency of the EQ-5D (0.73, 95% CI: 0.63-0.84; p.001). The SOSG-OQ score had no floor or ceiling effect indicating good coverage (median 30, range 3-64), whereas the EQ-5D had a ceiling effect of 10% (median 0.71, range 0.05-1).In conclusion, our study proposes a scoring methodology-after reversing four inversely scored items-for the SOSG-OQ and shows that the questionnaire is a valid tool for the assessment of quality of life in patients with metastatic spine disease. The SOSG-OQ is superior to the EQ-5D in terms of coverage and internal consistency but consists of more questions.

Background Context Patient-reported outcomes are becoming increasingly important when investigating results of patient and disease management. In sacral tumor, the symptoms of patients can vary substantially; therefore, no single questionnaire can adequately account for the full spectrum of symptoms and disability. Purpose The purpose of this study is to analyze redundancy within the current sacral tumor survey and make a recommendation for an updated version based on the results and patient and expert opinions. Study Design/Setting A survey study from a tertiary care orthopedic oncology referral center was used. Patient Sample The patient sample included 70 patients with sacral tumors (78% chordoma). Outcome Measures The following 10 questionnaires included in the current sacral tumor survey were evaluated: the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Item short form, PROMIS Pain Intensity short form, PROMIS Pain Interference short form, PROMIS Neuro-QOL v1.0 Lower Extremity Function short form, PROMIS v1.0 Anxiety short form, the PROMIS v1.0 Depression short form, the International Continence Society Male short form, the Modified Obstruction-Defecation Syndrome questionnaire, the PROMIS Sexual Function Profile v1.0, and the Stoma Quality of Life tool. Methods We performed an exploratory factor analysis to calculate the possible underlying latent traits. Spearman rank correlation coefficients were used to measure to what extent the questionnaires converged. We hypothesized the existence of six domains based on current literature: mental health, physical health, pain, gastrointestinal symptoms, sexual function, and urinary incontinence. To assess content validity, we surveyed 32 patients, 9 orthopedic oncologists, 1 medical oncologist, 1 radiation oncologist, and 1 orthopedic oncology nurse practitioner with experience in treating sacral tumor patients on the relevance of the domains. Results Reliability as measured by Cronbach alpha ranged from 0.65 to 0.96. Coverage measured by floor and ceiling effects ranged from 0% to 52% and from 0% to 30%, respectively. Explanatory factor analysis identified three traits to which the questionnaires that were expected to measure a similar construct correlated the most: mental health, physical function, and pain. Content validity index demonstrated low disagreement among patients (range: 0.10–0.18) and high agreement among physicians (range: 0.91–1.0) on the relevance of the proposed domains. Social health was identified by 50% of the commenting patients as an important yet missing domain. Conclusions The current sacral tumor survey is incomplete and time-consuming, and not all surveys are appropriate for the sacral tumor population. Our recommended survey contains less than half the questions and includes the newly recognized social health domain.

BACKGROUND In the treatment of spinal metastases the risks of surgery must be balanced against potential benefits, particularly in light of limited life-expectancy. Patient experiences and preferences regarding decision-making in this context are not well explored. PURPOSE We performed a qualitative study involving patients receiving treatment for spinal metastatic disease. We sought to understand factors that influenced decision-making around care for spinal metastases. STUDY SETTING Three tertiary academic medical centers. PATIENT SAMPLE We recruited patients presenting for treatment of spinal metastatic disease at one of three tertiary centers in Boston, MA. OUTCOME MEASURES We conducted semistructured interviews using a guide that probed participants’ experiences with making treatment decisions. METHODS We performed a thematic analysis that produced a list of themes, subthemes, and statement explaining how the themes related to the study's guiding questions. Patients were recruited until thematic saturation was reached. RESULTS We interviewed 23 participants before reaching thematic saturation. The enormity of treatment decisions, and of the diagnosis of spinal metastases itself, shaped participant preferences for who should take responsibility for the decision and whether to accept treatments bearing greater risk of complications. Pre-existing participant beliefs about decision-making and about surgery interacted with the clinical context in a way that tended to promote accepting physician recommendations and delaying or avoiding surgery. CONCLUSIONS The diagnosis of spinal metastatic disease played an outsized role in shaping participant preferences for agency in treatment decision-making. Further research should address strategies to support patient understanding of treatment options in clinical contexts—such as spinal metastases—characterized by ominous underlying disease and high-risk, often urgent interventions.

Background MicroRNAs are small, noncoding RNAs that regulate the expression of posttranslational genes. The presence of some specific microRNAs has been associated with increased risk of both local recurrence and metastasis and worse survival in patients with osteosarcoma. Pathologic fractures in osteosarcoma are considered to be more the manifestation of a neoplasm with a more aggressive biological behavior than the cause itself of worse prognosis. However, this has not been proved at the biological or molecular level. Currently, there has not been a microRNA profiling study of patients who have osteosarcoma with and without pathologic fractures that has described differences in terms of microRNA profiling between these two groups and their correlation with biologic behavior. Questions/purposes (1) In patients with osteosarcoma of the extremities, how do the microRNA profiles of those with and without pathologic fractures compare? (2) What relationship do microRNAs have with local recurrence, risk of metastasis, disease-specific survival, and overall survival in osteosarcoma patients with pathologic fractures? Methods Between 1994 and 2013, 217 patients were diagnosed and treated at our institution for osteosarcoma of the extremities. Patients were excluded if (1) they underwent oncologic resection of the osteosarcoma at an outside institution (two patients) or (2) they were diagnosed with an extraskeletal osteosarcoma (29 patients) or (3) they had less than 1 year of clinical follow-up and no oncologic outcome (local recurrence, metastasis, or death) (four patients). A total of 182 patients were eligible. Of those, 143 were high-grade osteosarcomas. After evaluation of tumor samples before chemotherapy treatment, a total of 80 consecutive samples were selected for sequencing. Demographic and clinical comparison between the sequenced and non-sequenced patients did not demonstrate any differences, confirming that both groups were comparable. Diagnostic samples from the extremities of 80 patients with high-grade extremity osteosarcomas who had not yet received chemotherapy underwent microRNA sequencing for an ongoing large-scale osteosarcoma genome profiling project at our institution. Six samples were removed after a second look by a musculoskeletal pathologist who verified cellularity and quality of samples to be sequenced, leaving a total of 74 patients. Of these, two samples were removed as they were confirmed to be pelvic tumors in a second check after sequencing. The final study sample was 72 patients (11 patients with pathologic fractures and 61 without). Sequencing data were correlated with fractures and local recurrence, risk of metastasis, disease-specific survival, and overall survival through Kaplan-Meier analyses. Results Several microRNAs were expressed differently between the two groups. Among the markers with the highest differential expression (edgeR and DESeq algorithms), Hsa-mIR 656-3p, hsa-miR 493-5p, and hsa-miR 381-3p were upregulated in patients with pathologic fractures, whereas hsa-miR 363, hsa-miR 885-5p, and has-miR 20b-5p were downregulated. The highest differential expression fracture and nonfracture-associated microRNA markers also distinguished groups of patients with different metastasis risk, a well as different disease-specific and overall survival. Furthermore, the profile of pathologic fractures demonstrated a higher differential expression for microRNA markers that were previously associated with a higher risk of metastasis and lower survival rates in patients with osteosarcoma. Conclusions In patients who have osteosarcoma, the microRNA profiles of those with pathologic fractures are different than of patients without pathologic fractures. The highest differential expression mircroRNA molecules in patients with pathologic fractures predict also higher risk of metastatic disease as well as worse disease-specific survival and overall survival. Furthermore, we found higher differential expression of microRNAs in the pathologic fracture group previously associated with poor prognosis. The higher risk of metastasis and poorer overall survival in patients with pathologic fractures is inherent to tumor aggressive biologic behavior. It is plausible that the fracture itself is not the direct cause of worse prognosis but another manifestation of tumor biologic aggressiveness. Identification of these molecules through liquid biopsies may help to determine which patients may benefit from surgery before fractures occur. The same technology can be applied to identify patterns of response to conventional chemotherapy, assisting in more specific and accurate systemic therapy. Level of evidence level III, prognostic study.