A comparative study of spinal cord compression management in metastatic prostate cancer: Teaching versus non-teaching hospitals in the United States.

BACKGROUND: Spinal cord compression (SCC) in metastatic prostate cancer (MPC) is a critical complication and multiple factors influence the optimal therapeutic strategy. We investigated the differences in practice patterns between teaching hospitals (TH) and non-teaching hospitals (NTH) across the United States. METHOD: Using the National Inpatient Sample Database (NIS), we performed a retrospective study on hospitalizations with MPC and SCC between 2016 and 2020 in US. We compared demographic factors, comorbidities, treatment modalities, duration of hospitalization, financial expenditures, and mortality between TH and NTH. We also examined the patients' characteristics and outcomes in TH and NTH based on their chosen therapeutic strategy. RESULTS: We identified 11,380 admissions with metastatic prostate cancer and SCC; 9610 in TH and 1770 in NTH. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH. Although the median age and Charlson comorbidity score did not differ between two groups, patients in TH were more likely to receive intervention (radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs. 23.0% in NTH & Radiation: 12.1% in TH vs. 8.2% in NTH). Mortality was lower in TH than NTH (4.5% vs. 7.9%). In both TH and NTH, a higher proportion of patients with private insurance underwent surgery (TH: Surgery 25.1% vs. Radiation 18.8% & NTH: Surgery 27.0% vs. 6.9%). Black patients were more likely to receive radiation than surgery in TH (34.2% vs. 26.8%). CONCLUSION: This study showed a greater percentage of patients underwent surgical intervention at TH compared to NTH. Additionally, the type of insurance and racial background were associated with distinctive treatment approaches.

Prognostic Scoring System Development for Malignant Spinal Cord Compression.

OBJECTIVE: Although many prognostic scoring systems have been used to predict survival of malignant spinal cord compression (MSCC) patients, some previous data have shown that the accuracy of the scoring system remains problematic. Current advanced cancer therapies may influence the altered survival predictions. The aim of this study was to develop a new prognostic scoring system for higher accuracy of survival prediction in patients with malignant spinal cord compression (MSCC). METHODS: Data were collected from 89 patients diagnosed with MSCC in 2018-2020. Potential clinical factors were analyzed using univariate and multivariate Cox's regression analysis. The selected logistic coefficients were transformed into a prognostic predictive scoring system. Internal validation was performed using the bootstrapping procedure. RESULTS: According to multivariate Cox's regression analysis, 9 potential prognostic factors were obtained, i.e. Neutrophil-to-Lymphocyte ratio >3.6, breast cancer, lung cancer, other types of cancer (except prostate cancer), male, complete paralysis, spinal metastases in three levels, hypercalcemia, and no further systemic treatment. The data was developed into a Buddhasothorn Hospital Malignant Spinal Cord Compression (BSH-MSCC) score with an interval of 0-52 points (AUC = 0.77; AUC to predict short-term survival = 0.93). When using the cut-off point > 18 to predict short-term survival, AUC = 0.84, sensitivity = 81.5%, specificity = 85.7%, PPV = 89.8%, and NPV = 75.0%. Internal validation with 1,000 bootstrap resampling showed good discrimination. CONCLUSION: BSH-MSCC score had a simplified score and high accuracy. The new tool is more accurate and can help decision-making for better treatment using a multidisciplinary approach.

A Personalized Medicine Approach for the Management of Spinal Metastases with Cord Compression: Development of a Novel Clinical Prediction Model for Postoperative Survival and Quality of Life.

Surgery should be considered for patients with metastatic epidural spinal cord compression (MESCC) with a life expectancy of ≥3 months. Given the heterogeneity of the clinical presentation and outcomes, clinical prognostic models (CPMs) can assist in tailoring a personalized medicine approach to optimize surgical decision-making. We aimed to develop and internally validate the first CPM of health-related quality of life (HRQoL) and a novel CPM to predict the survival of patients with MESCC treated surgically. Using data from 258 patients (AOSpine North America MESCC study and Nottingham MESCC registry), we created 1-year survival and HRQoL CPMs using a Cox model and logistic regression analysis with manual backward elimination. The outcome measure for HRQoL was the minimal clinical important difference in EuroQol 5-dimension questionnaire scores. Internal validation involved 200 bootstrap iterations, and calibration and discrimination were evaluated. Longer survival was associated with a higher SF-36 physical component score (hazard ratio [HR], 0.96). In contrast, primary tumor other than breast, thyroid, or prostate (unfavorable: HR, 2.57; other: HR, 1.20), organ metastasis (HR, 1.51), male sex (HR, 1.58), and preoperative radiotherapy (HR, 1.53) were not (c-statistic, 0.69; 95% confidence interval, 0.64-0.73). Karnofsky performance status <70% (odds ratio [OR], 2.50), living in North America (OR, 4.06), SF-36 physical component score (OR, 0.95) and SF-36 mental component score (OR, 0.96) were associated with the likelihood of achieving a minimal clinical important difference improvement in the EuroQol 5-Dimension Questionnaire score at 3 months (c-statistic, 0.74; 95% confidence interval, 0.68-0.79). The calibration for both CPMs was very good. We developed and internally validated the first CPMs of survival and HRQoL at 3 months postoperatively in patients with MESCC using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) guidelines. A web-based calculator is available (available at: http://spine-met.com) to assist with clinical decision-making.

A new and simple scoring system to predict overall survival after irradiation for metastatic spinal cord compression.

PURPOSE: To develop a model that predicts survival in patients irradiated for metastatic spinal cord compression (MSCC), hence assisting in the decision between a short and a long-course radiotherapy (RT) regimen. METHODS: 138 patients diagnosed with MSCC and treated with RT alone were included. Based on a multivariate analysis, a scoring system was developed. It included four prognostic variables: age, number of vertebrae, ECOG and histology. Total scores ranged between 14 and 24 points and patients were divided into two groups. RESULTS: The 6-month survival rate was 22% for patients with a score of 14-18 points; and 69% for patients with a score of 19-24 points (P < 0.001). The system exhibits a high specificity and positive predictive value and an appropriate discriminative ability. CONCLUSIONS: Patients with scores between 19 and 24 points were found to survive longer, thus a long-course RT appears to be more appropriate.

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial.

Importance: Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. Objective: To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. Design, Setting, and Participants: Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. Interventions: Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). Main Outcomes and Measures: The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was -11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. Results: Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, -3.5% [1-sided 95% CI, -11.5% to ∞]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was -0.4% (63.9% vs 64.3%; [1-sided 95% CI, -6.9 to ∞]; P value for noninferiority = .004) at week 1, -0.7% (66.8% vs 67.6%; [1-sided 95% CI, -8.1 to ∞]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, -4.6 to ∞]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. Conclusions and Relevance: Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding. Trial Registration: ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008.

The impact of surgical timing on neurological outcomes and survival in patients with complete paralysis caused by spinal tumours: evaluation of surgery on patients with complete paralysis due to neoplastic epidural spinal cord compression.

AIMS: The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression. PATIENTS AND METHODS: The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery. RESULTS: A total of 52 patients (38.5%) achieved American Spinal Injury Association Impairment Scale (AIS) D or E recovery postoperatively. The timing of surgery (p = 0.003) was found to be significant in univariate analysis. In multivariate analysis, surgery within one week was associated with better neurological recovery than surgery within three weeks (p = 0.002), with a trend towards being associated with a better neurological recovery than surgery within one to two weeks (p = 0.597) and two to three weeks (p = 0.055). Age (p = 0.039) and muscle tone (p = 0.018) were also significant predictors. In Cox regression analysis, good neurological recovery (p = 0.004), benign tumours (p = 0.039), and primary tumours (p = 0.005) were associated with longer survival. Calibration graphs showed that the nomogram did well with an ideal model. The bootstrap-corrected C-index for neurological recovery was 0.72. CONCLUSION: In patients with complete paralysis due to neoplastic spinal cord compression, whose treatment is delayed for more than 48 hours from the onset of symptoms, surgery within one week is still beneficial. Surgery undertaken at this time may still offer neurological recovery and longer survival. The identification of the association between these factors and neurological recovery may help guide treatment for these patients. Cite this article: Bone Joint J 2019;101-B:872-879.

Percutaneous Balloon Kyphoplasty and Short Instrumentation Compared with Traditional Long Instrumentation for Thoracolumbar Metastatic Spinal Cord Compression.

BACKGROUND: A considerable propotion of patients with cancer got thoracolumbar vertebral metastatic epidural spinal cord compression, which affected their quality of life. Traditional surgical management involves early decompression with concomitant spine stabilization with long instrumentation. However, complications are caused by massive blood loss and long operation time. This study aimed to compare the safety and efficacy of short posterior instrumentation with kyphoplasty and the traditional method for thoracolumbar metastatic epidural spinal cord compression. METHODS: Between January 2004 and December 2015, a retrospective study was conducted on 120 patients with metastatic epidural spinal cord compression from T6 to L5 and divided into 2 groups: short posterior instrumentation with the balloon kyphoplasty group (group I, n = 50) and the long posterior instrumentation group (group II, n = 70). The clinical and radiographic parameters of patients in the 2 groups were compared with a nonrandomized cohort method. Patients were followed up from 3 to 40 months after surgery according to survival time. RESULTS: In group I, the surgery had a mean blood loss of 650 mL and a survival time of 19.1 months. In group II, the surgery had a mean blood loss of 2100 mL and a survival time of 14.14 months. A significant difference in blood loss amount (P = 0.002) was observed. Complications, including deep wound infection, durotomy, and uncontrolled bleeding, were observed in both groups. No postoperative cement-induced neurologic deterioration, implant failure occurred. CONCLUSIONS: Kyphoplasty with short posterior instrumentation is a novel technique that can be performed safely and effectively for the treatment of thoracolumbar metastatic epidural spinal cord compression. Rigid stability, reduced blood loss, and short fixation decrease surgical morbidity of spinal metastasis.

Predictors of Outcomes and a Scoring System for Estimating Survival in Patients Treated With Radiotherapy for Metastatic Spinal Cord Compression From Small-Cell Lung Cancer.

PURPOSE: To identify prognostic factors and create a survival score to facilitate individualized care of patients with metastatic spinal cord compression (MSCC) from small-cell lung cancer (SCLC). PATIENTS AND METHODS: Radiation regimen plus 9 factors were retrospectively evaluated in 120 patients irradiated for MSCC from SCLC for overall response, improvement of motor deficits, postradiotherapy ambulatory status, local control of MSCC, and overall survival (OS). Factors included age, interval diagnosis of SCLC to radiotherapy (RT) of MSCC, visceral metastases, further bone metastases, gender, time developing motor deficits, pre-RT ambulatory status, number of affected vertebrae, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Improvement of motor deficits showed significant associations with ECOG PS 1-2 (P = .018); time developing motor deficits achieved borderline significance (P = .059). Post-RT ambulatory status was significantly associated with slower development of motor dysfunction (P = .003), ambulatory status (P < .001), and ECOG PS 1-2 (P < .001). No factor was significantly associated with overall response and local control. On multivariate analysis, OS was significantly associated with interval from SCLC diagnosis to RT of MSCC (P = .004), visceral metastases (P < .001), ambulatory status (P = .002), and ECOG PS (P = .002). For the survival score, 6-month OS rates related to each of these factors were divided by 10. Patient scores were obtained by adding these factors' scores. Three groups were defined (5, 7-13, and 15-17 points) with 6-month OS rates of 0, 18%, and 77%, respectively (P < .001). CONCLUSION: Predictors of various outcomes were identified and a survival score was created that can support physicians aiming to create personalized treatments to patients with MSCC from SCLC.

Prognostic Differences in Patients with Solitary and Multiple Spinal Metastases.

OBJECTIVES: To investigate the association between the number of metastases to the spine and survival in patients with metastatic spinal cord compression (MSCC), as well as the prognosis difference between patients with solitary spinal metastasis (SSM) and multiple spinal metastases (MSM). METHODS: Three institutional databases were searched to identify all patients who had undergone spinal surgery for metastatic spinal tumors between March 2002 and June 2010. As well as age and gender, preoperative medical conditions were collected from medical records, including primary tumor, preoperative Frankel score, other bone metastases, preoperative Karnofsky performance status (KPS), number of involved vertebrae, pathological fracture metastasis site, serum albumin, sphincter dysfunction and the time of developing motor deficits before surgery. Survival data were obtained from medical records or via telephone follow-ups. Univariate and multivariate predictors of overall survival for each group were assessed using the Cox proportional hazards model. RESULTS: The median postoperative survival time was 6.0 ± 0.6 months (95% confidence interval [CI] 4.8-7.2) in patients with SSM and 7.0 ± 1.0 months (95% CI 5.1-8.9) in patients with MSM (P = 0.238). The difference in survival was not significant between groups. Furthermore, univariate analysis showed that the number of spinal metastases had no significant association with survival (P = 0.075). Primary tumor (P = 0.004) and preoperative KPS (P < 0.001) were independent prognostic factors in the whole cohort; primary tumor (P = 0.020), time of developing motor deficit (P = 0.041) and preoperative KPS (P = 0.038) were independent prognostic factors in patients with SSM; while preoperative KPS (P = 0.001) and serum album level (P < 0.001) were independent prognostic factors in patients with MSM. CONCLUSION: The number of spinal metastases has not proven to be useful in predicting the prognosis for patients with MSCC. Consequently, more aggressive operations should be considered for patients with multiple spinal metastases.

Surgical Management and Factors Affecting the Prognosis for Patients with Thyroid Cancer Spinal Metastases: A Retrospective Analysis of 52 Consecutive Patients from a Single Center.

BACKGROUND: Thyroid cancer, one of the most common endocrine malignancies in developed areas and China, is associated with favorable prognosis. However, the presence of spinal metastases will remarkably reduce the life expectancy for patients with thyroid cancer. In addition, limited information is available about such disease. METHODS: Various potential clinical factors were submitted to univariate and multivariate analyses to identify the independent variables that predicted the prognosis for patients. In addition, the survival rate was estimated according to the Kaplan-Meier method, and statistic differences were calculated by the log-rank test. Moreover, factors with a P value of ≤0.1 were performed multivariate analysis using a multivariate Cox proportional hazards model, and factors with a P value of <0.05 were considered as statistically significant. RESULTS: Seven potential independent prognostic factors had been identified through univariate analysis, which were then subjected to multivariate analysis. Our results suggested that age of ≤50 years, single segment involved, and follicular thyroid cancer were the independent favorable prognostic factors. CONCLUSIONS: Findings in this study indicate that age of ≤50 years, single segment involved, and follicular thyroid cancer are favorable prognostic factors for patients with thyroid cancer spinal metastases.

Steroid Use Associated With Increased Odds of 30-Day Mortality in Surgical Patients With Metastatic Spinal Tumors in the Setting of Disseminated Disease.

BACKGROUND: Steroid administration is part of a standard treatment regimen in metastatic spinal cord compression, though the appropriate dose, duration, efficacy, and risks remain controversial. OBJECTIVE: To analyze the risk of preoperative steroid use on 30-d mortality in surgical metastatic spinal tumors with dissemination disease using a large multicenter national database. METHODS: Adult patients who underwent surgical treatment for metastatic spine tumors between 2005 and 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Demographic, preoperative risk factors, operative information, and postoperative events were extracted. Multivariate logistical regression modeling was used to investigate the association with preoperative steroid use with the outcome of interest, 30-d mortality. Other independent risk factors associated with 30-d mortality were also identified. RESULTS: Five hundred fifty-two patients underwent surgical treatment of spinal metastases with disseminated cancer present at time of surgery. Independent risk factors of 30-d mortality included prolonged steroid use (odds ratio [OR] 2.48, 95% confidence interval [CI]: 1.22-5.04, P = .012), dependent functional status (OR 2.91, 95% CI: 1.68-5.04, P < .001), history of bleeding disorder (OR 2.80, 95% CI: 1.16-6.74, P = .021), history of smoking (OR 2.26, 95% CI: 1.11-4.61, P = .024), preoperative transfusions (OR 2.91, 95% CI: 1.02-8.29, P = .049), and preoperative infection/sepsis (OR 2.67, 95% CI: 1.18-6.08, P = .02). Our model demonstrates very strong predictive capabilities, with an area under the receiver operating characteristic curve of 0.7447. CONCLUSION: Steroid use is associated with a significant increased risk of 30-d mortality in surgical metastatic spine tumor patients with disseminated disease. These findings warrant further investigation in controlled experimental environments.

Prognostic Discrepancy on Overall Survival Between Ambulatory and Nonambulatory Patients with Metastatic Spinal Cord Compression.

BACKGROUND: Contradictory results have been reported regarding the prognostic effect of ambulatory status in patients with metastatic spinal cord compression (MSCC). The aim of this study was to investigate whether ambulatory status is a significant predictor of overall survival in patients with MSCC and to distinguish the differences of predictors between patients who were ambulatory and those who were not ambulatory before operation. METHODS: Three clinical centers were retrospectively reviewed to identify patients operated on for MSCC between 2005 and 2015. Fourteen prognostic factors were analyzed using Kaplan-Meier survival curves, univariate log-rank test, and multivariate Cox hazard regression model for the whole cohort and the subgroups of ambulatory and nonambulatory patients. RESULTS: In all, 169 patients were consecutively enrolled. Their mean age was 59.6 ± 10.5 years (range, 18-84 years). The median survival time in the whole cohort was 7.0 ± 0.5 months, whereas it was 7.0 ± 0.8 months and 5.0 ± 1.3 months in ambulatory and nonambulatory patients, respectively. Multivariate Cox regression analysis showed that ambulatory status was not a significant predictor of overall survival (P = 0.266), but primary tumor type and Karnofsky performance status were independent predictors of overall survival for the whole cohort. Primary tumor and metastatic site were significantly associated with survival in ambulatory patients. Gender and Karnofsky performance status were associated with survival in nonambulatory patients. CONCLUSIONS: Ambulatory status was not shown to predict the prognosis of patients with MSCC. prognostic factors should be distinguished between ambulatory and nonambulatory patients when choosing a therapeutic modality.

Prognostic Factors and a Survival Score in Patients Irradiated for Metastatic Epidural Spinal Cord Compression from Urothelial Carcinoma Cancer of the Bladder.

BACKGROUND/AIM: Prognoses of patients with metastatic epidural spinal cord compression (MESCC) from urothelial carcinoma of the bladder are generally poor. This study aimed to identify prognostic factors that can facilitate personalized care of these patients. PATIENTS AND METHODS: In 46 patients, 10 factors were evaluated for overall response (OR), post-radiotherapy (RT) ambulatory status, local control of MESCC and overall survival (OS). Independent predictors of OS were incorporated in a scoring system. RESULTS: Being ambulatory post-RT was associated with pre-RT ambulatory status (p<0.001) and better performance score (p<0.001). No factor was significantly associated with OR and local control. On multivariate analyses, lack of visceral metastases (p=0.002), being ambulatory pre-RT (p=0.001) and performance score 1-2 (p=0.004) were associated with improved OS. Based on these factors, there were three distinct prognostic groups with 0, 1-2 and 3 points and median OS times of 2, 4 and 11.5 months, respectively. CONCLUSION: Prognostic factors were identified and a new survival score was created that will help physicians aiming to personalize treatment for patients with MESCC from urothelial carcinoma of the bladder.

A scoring system to predict local progression-free survival in patients irradiated with 20 Gy in 5 fractions for malignant spinal cord compression.

BACKGROUND: Local progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery. METHODS: In 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added. RESULTS: On multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24-28 (A), 29-31 (B) and 32-35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached). CONCLUSIONS: Most group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT.

Predictive factors of survival in a surgical series of metastatic epidural spinal cord compression and complete external validation of 8 multivariate models of survival in a prospective North American multicenter study.

BACKGROUND: This study was designed to identify preoperative predictors of survival in surgically treated patients with metastatic epidural spinal cord compression (MESCC), to examine how these predictors are related to 8 prognostic models, and to perform the first full external validation of these models in accordance with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. METHODS: One hundred forty-two surgically treated patients with MESCC were enrolled in a prospective, multicenter North American cohort study and were followed for 12 months or until death. Cox regression was used. Noncollinear predictors with < 10% missing data, with ≥ 10 events per stratum, and with P < .05 in a univariate analysis were tested through a backward stepwise selection. For the original and revised Tokuhashi prognostic scoring systems (PSSs), Tomita PSS, modified Bauer PSS, van der Linden PSS, Bartels model, Oswestry Spinal Risk Index, and Bollen PSS, this study examined calibration graphically, discrimination with Harrell c-statistics, and survival stratified by risk groups with the Kaplan-Meier method and log-rank test. RESULTS: The following were significant in the univariate analysis: type of primary tumor, sex, organ metastasis, body mass index, preoperative radiotherapy to MESCC, physical component (PC) of the 36-Item Short Form Health Survey, version 2 (SF-36v2), and EuroQol 5-Dimension (EQ-5D) Questionnaire. Breast, prostate and thyroid primary tumor (HR: 2.9; P =.0005), presence of organ metastasis (hazard ratio (HR): 2.0; P = .005) and SF-36v2 PC (HR: 0.95; P < .0001) were associated with survival in multivariable analysis. Predicted prognoses poorly matched observed values on calibration plots; Bartels model calibration slope was 0.45. Bollen PSS (0.61; 95% CI: 0.58-0.64) and Bartels model (0.68; 95% CI: 0.65-0.71) had the lowest and highest c-statistics, respectively. CONCLUSIONS: The primary tumor type (breast, prostate, or thyroid), an absence of organ metastasis, and a lower degree of physical disability are preoperative predictors of longer survival for surgical MESCC patients. These results are in keeping with current models. This full external validation of 8 prognostic PSSs or model of survival in surgical MESCC patients has revealed that calibration is poor, especially for long-term survivors, whereas discrimination is possibly helpful.

Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study.

BACKGROUND: Multiple myeloma is characterised by monoclonal paraprotein production and osteolytic lesions, commonly leading to skeletal-related events (spinal cord compression, pathological fracture, or surgery or radiotherapy to affected bone). Denosumab, a monoclonal antibody targeting RANKL, reduces skeletal-related events associated with bone lesions or metastases in patients with advanced solid tumours. This study aimed to assess the efficacy and safety of denosumab compared with zoledronic acid for the prevention of skeletal-related events in patients with newly diagnosed multiple myeloma. METHODS: In this international, double-blind, double-dummy, randomised, active-controlled, phase 3 study, patients in 259 centres and 29 countries aged 18 years or older with symptomatic newly diagnosed multiple myeloma who had at least one documented lytic bone lesion were randomly assigned (1:1; centrally, by interactive voice response system using a fixed stratified permuted block randomisation list with a block size of four) to subcutaneous denosumab 120 mg plus intravenous placebo every 4 weeks or intravenous zoledronic acid 4 mg plus subcutaneous placebo every 4 weeks (both groups also received investigators' choice of first-line antimyeloma therapy). Stratification was by intent to undergo autologous transplantation, antimyeloma therapy, International Staging System stage, previous skeletal-related events, and region. The clinical study team and patients were masked to treatment assignments. The primary endpoint was non-inferiority of denosumab to zoledronic acid with respect to time to first skeletal-related event in the full analysis set (all randomly assigned patients). All safety endpoints were analysed in the safety analysis set, which includes all randomly assigned patients who received at least one dose of active study drug. This study is registered with ClinicalTrials.gov, number NCT01345019. FINDINGS: From May 17, 2012, to March 29, 2016, we enrolled 1718 patients and randomly assigned 859 to each treatment group. The study met the primary endpoint; denosumab was non-inferior to zoledronic acid for time to first skeletal-related event (hazard ratio 0·98, 95% CI 0·85-1·14; pnon-inferiority=0·010). 1702 patients received at least one dose of the investigational drug and were included in the safety analysis (850 patients receiving denosumab and 852 receiving zoledronic acid). The most common grade 3 or worse treatment-emergent adverse events for denosumab and zoledronic acid were neutropenia (126 [15%] vs 125 [15%]), thrombocytopenia (120 [14%] vs 103 [12%]), anaemia (100 [12%] vs 85 [10%]), febrile neutropenia (96 [11%] vs 87 [10%]), and pneumonia (65 [8%] vs 70 [8%]). Renal toxicity was reported in 85 (10%) patients in the denosumab group versus 146 (17%) in the zoledronic acid group; hypocalcaemia adverse events were reported in 144 (17%) versus 106 (12%). Incidence of osteonecrosis of the jaw was not significantly different between the denosumab and zoledronic acid groups (35 [4%] vs 24 [3%]; p=0·147). The most common serious adverse event for both treatment groups was pneumonia (71 [8%] vs 69 [8%]). One patient in the zoledronic acid group died of cardiac arrest that was deemed treatment-related. INTERPRETATION: In patients with newly diagnosed multiple myeloma, denosumab was non-inferior to zoledronic acid for time to skeletal-related events. The results from this study suggest denosumab could be an additional option for the standard of care for patients with multiple myeloma with bone disease. FUNDING: Amgen.

Ambulation and survival following surgery in elderly patients with metastatic epidural spinal cord compression.

BACKGROUND AND CONTEXT: Metastatic epidural spinal cord compression (MESCC) is a disabling consequence of disease progression. Surgery can restore or preserve physical function, improving access to treatments that increase duration of survival; however, advanced patient age may deter oncologists and surgeons from considering surgical management. PURPOSE: Evaluate the duration of ambulation and survival in elderly patients following surgical decompression of MESCC. STUDY DESIGN/SETTING: Retrospective file review of a prospective database, under institutional review board (IRB) waiver of informed consent, of consecutive patients treated in an academic tertiary care medical center from August 2008 to March 2015. PATIENT SAMPLE: Patients ≥65 years presenting neurological and/or radiological signs of cord compression because of metastatic disease, who underwent surgical decompression. OUTCOME MEASURES: Duration of ambulation and survival. METHODS: Patients underwent urgent multidisciplinary evaluation and surgery. Ambulation and survival were compared with age, pre-, and postoperative neurological (American Spinal Injury Association [ASIA] Impairment Scale [AIS]) and performance status (Karnofsky Performance Status [KPS]), and Tokuhashi Score using Kruskal-Wallis and Wilcoxon signed rank tests, Pearson correlation coefficient, Cox regression model, log-rank analysis, and Kaplan-Meier analysis. RESULTS: Forty patients were included (21 male, 54%; mean age 74 years, range 65-87). Surgery was performed a mean 3.8 days after onset of motor symptoms. Mean duration of ambulation and survival were 474 (range 0-1662) and 525 days (range 11-1662), respectively; 53% of patients (21 of 40) survived and 43% (17 of 40) retained ambulation for ≥1 year. There was no significant relationship between survival and ambulation for patients aged 65-69, 70-79, or 80-89 years, although Kaplan-Meier analysis suggested stratification. There was a significant relationship between duration of ambulation and pre- and postoperative AIS (p=.0342, p=.0358, respectively) and postoperative KPS (p=.0221). Tokuhashi score was not significantly related to duration of survival or ambulation, and greatly underestimated life expectancy in 22 of 37 (59%) patients with scores 0-11. CONCLUSIONS: Decompressive surgery led to marked improvement in neurological function and performance status. More than 50% of patients survived for >1 year, some for 3 years or more after surgery.

Survival analysis of malignant epidural spinal cord compression after palliative radiotherapy using Tokuhashi scoring system and the impact of systemic therapy.

BACKGROUND: Previous studies have shown similar clinical outcomes of both single and multi-fraction (Fr) radiation therapy among malignant epidural spinal cord compression (MSCC) patients with poor prognosis; whereas, patients expected to have longer survival may require long-course radiotherapy to prevent local failure. However, such a poor prognosis risk group has not yet been clearly identified for use in daily clinical practice. We examined if the known predictive Tokuhashi scoring system could be adapted in MSCC patients treated with palliative radiation therapy. METHODS: A retrospective review of the treatment outcomes of MSCC patients who received palliative radiotherapy from January 2014 to May 2015 was conducted. The patients were stratified into two groups according to the Tokuhashi scoring system: group 1 (score <9), expected survival <6 months, and group 2 (score >8), expected survival >6 months. Their survival was tested against subsequent systemic therapy (chemotherapy, targeted or hormonal therapy) and other risk factors including age, primary site, visceral metastasis, baseline motor function, prior radiotherapy and radiotherapy fractionation (single or multiple). RESULTS: The outcomes of 119 patients were studied, 116 (97.5%) patients had already succumbed. The overall median survival was 55 days (range, 4-576 days). Ninety-three patients (78.2%) belonged to group 1. The median dose delivered was 25 Gy in 5 Frs [range, 7 Gy in 2 Frs-40 Gy in 10 Frs (to the cauda equina)]. Only nine patients (7.6%) received single-Fr radiotherapy, all belonging to Tokuhashi group 1. Patients belonging to group 1 had shorter median survival than group 2; 49 and 108 days, respectively (P=0.003). Among all the patients, subsequent systemic treatment [hazard ratio (HR) =0.407; 95% confidence interval (CI), 0.236-0.702; P=0.001], non-visceral metastasis (HR =0.608; 95% CI, 0.387-0.956; P=0.031) and primary lung or breast or prostate cancer (P=0.029) were associated with better survival in multivariate analysis. For patients in group 1, primary breast or prostate cancer (HR =0.264; 95% CI, 0.122-0.572; P=0.001) or lung cancer (HR =0.421; 95% CI, 0.246-0.719; P=0.002), non-visceral metastasis (HR =0.453; 95% CI, 0.264-0.777; P=0.004), multi-Fr (HR =0.455; 95% CI, 0.217-0.956; P=0.038) and subsequent systemic therapy (HR =0.460; 95% CI, 0.252-0.842; P=0.012) were associated with better survival. The survival of a subset of patients in group 1 without subsequent systemic therapy was dismal (median survival only 40 days) and not altered by radiotherapy schedule (P=0.189). CONCLUSIONS: MSCC comprises a very heterogenous group of patients, even under the Tokuhashi grouping. Systemic therapy or visceral metastasis may be more important prognostic factors. Further studies are necessary to better select the poor prognosis risk group. In clinical practice, single-Fr radiotherapy could be considered in Tokuhashi group 1 patients due to their expected short survival, especially for those without reasonable systemic treatment options.

Impact of Symptomatic Metastatic Spinal Cord Compression on Survival of Patients with Non-Small-Cell Lung Cancer.

OBJECTIVES: Non-small-cell lung cancer (NSCLC) is one of the most common primary tumor sites among patients with metastatic spinal cord compression (MSCC). This disorder is related to neurologic dysfunction and can reduce the quality of life, but the association between MSCC and death is unclear. The aim of this study was to analyze the impact of the occurrence of symptomatic MSCC on overall survival of patients with NSCLC. METHODS: A cohort study was carried out involving 1112 patients with NSCLC who were enrolled between 2006 and 2014 in a single cancer center. Clinical and sociodemographic data were extracted from the physical and electronic records. Survival analysis of patients with NSCLC was conducted using the Kaplan-Meier method. A log-rank test was used to assess differences between survival curves. Cox proportional hazards regression analyses were carried out to quantify the relationship between the independent variable (MSCC) and the outcome (overall survival). RESULTS: During the study period, the incidence of MSCC was 4.1%. Patients who presented with MSCC were 1.43 times more likely to die than were those with no history of MSCC (hazard ratio, 1.43; 95% confidence interval [CI], 1.03-2.00; P = 0.031). The median survival time was 8.04 months (95% CI, 6.13-9.96) for those who presented MSCC and 11.95 months (95% CI, 10.80-13.11) for those who did not presented MSCC during the course of disease (P = 0.002). CONCLUSIONS: MSCC is an important and independent predictor of NSCLC worse survival. This effect was not influenced by sociodemographic and clinical factors.