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.

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.

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.

Metastatic spinal cord compression as the first sign of malignancy.

Background and purpose - Metastatic spinal cord compression (MSCC) as the initial manifestation of malignancy (IMM) limits the time for diagnostic workup; most often, treatment is required before the final primary tumor diagnosis. We evaluated neurological outcome, complications, survival, and the manner of diagnosing the primary tumor in patients who were operated for MSCC as the IMM. Patients and methods - Records of 69 consecutive patients (51 men) who underwent surgery for MSCC as the IMM were reviewed. The patients had no history of cancer when they presented with pain (n = 2) and/or neurological symptoms (n = 67). Results - The primary tumor was identified in 59 patients. In 10 patients, no specific diagnosis could be established, and they were therefore defined as having cancer of unknown primary tumor (CUP). At the end of the study, 16 patients were still alive (median follow-up 2.5 years). The overall survival time was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas patients with prostate cancer (6 years) and myeloma (5 years) had the longest survival. 20 of the 39 patients who were non-ambulatory preoperatively regained walking ability, and 29 of the 30 ambulatory patients preoperatively retained their walking ability 1 month postoperatively. 15 of the 69 patients suffered from a total of 20 complications within 1 month postoperatively. Interpretation - Postoperative survival with MSCC as the IMM depends on the type of primary tumor. Surgery in these patients maintains and improves ambulatory function.

Decompression surgery for spinal metastases: a systematic review.

OBJECTIVE The aim of this study was to systematically review the literature on reported outcomes following decompression surgery for spinal metastases. METHODS The authors conducted MEDLINE, Scopus, and Web of Science database searches for studies reporting clinical outcomes and complications associated with decompression surgery for metastatic spinal tumors. Both retrospective and prospective studies were included. After meeting inclusion criteria, articles were categorized based on the following reported outcomes: survival, ambulation, surgical technique, neurological function, primary tumor histology, and miscellaneous outcomes. RESULTS Of the 4148 articles retrieved from databases, 36 met inclusion criteria. Of those included, 8 were prospective studies and 28 were retrospective studies. The year of publication ranged from 1992 to 2015. Study size ranged from 21 to 711 patients. Three studies found that good preoperative Karnofsky Performance Status (KPS ≥ 80%) was a significant predictor of survival. No study reported a significant effect of time-to-surgery following the onset of spinal cord compression symptoms on survival. Three studies reported improvement in neurological function following surgery. The most commonly cited complication was wound infection or dehiscence (22 studies). Eight studies reported that preoperative ambulatory or preoperative motor status was a significant predictor of postoperative ambulatory status. A wide variety of surgical techniques were reported: posterior decompression and stabilization, posterior decompression without stabilization, and posterior decompression with total or subtotal tumor resection. Although a wide range of functional scales were used to assess neurological outcomes, four studies used the American Spinal Injury Association (ASIA) Impairment Scale to assess neurological function. Four studies reported the effects of radiation therapy and local disease control for spinal metastases. Two studies reported that the type of treatment was not significantly associated with the rate of local control. The most commonly reported primary tumor types included lung cancer, prostate cancer, breast cancer, renal cancer, and gastrointestinal cancer. CONCLUSIONS This study reports a systematic review of the literature on decompression surgery for spinal metastases. The results of this study can help educate surgeons on the previously published predictors of outcomes following decompression surgery for metastatic spinal disease. However, the authors also identify significant gaps in the literature and the need for future studies investigating the optimal practice with regard to decompression surgery for spinal metastases.

Prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression from non-small cell lung cancer.

BACKGROUND: The aim of this study was to develop a scoring system for prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed nine preoperative characteristics for survival in a series of 64 patients with NSCLC who were operated with posterior decompression and spine stabilization for MSCC. Characteristics significantly associated with survival on multivariate analysis were included in the scoring system. The scoring point for each significant characteristic was derived from the hazard ratios on Cox proportional hazards model. The total score for each patient was obtained by adding the scoring points of all significant characteristics. RESULTS: Eastern Cooperative Oncology Group (ECOG) performance status, number of involved vertebrae, visceral metastases, and time developing motor deficits had significant impact on survival on multivariate analysis and were included in the scoring system. According to the prognostic scores, which ranged from 4 to 10 points, three prognostic groups were designed: 4-5 points (n = 22), 6-7 points (n = 23), and 8-10 points (n = 19). The corresponding 6-month survival rates were 95, 47 and 11%, respectively (P < 0.0001). In addition, the functional outcome was worse in the group of patients with 8-10 points compared with other two prognostic groups. CONCLUSIONS: The new scoring system will enable physicians to identify patient with MSCC from NSCLC who may be a candidate for decompression and spine stabilization, more radical surgery, or supportive care alone. Patients with scores of 4-5, who have the most favorable survival prognosis and functional outcome, can be treated with more radical surgery in order to realize better local control of disease and prevent the occurrence of local disease. Patients with scores of 6-7 points should be surgical candidates, because survival prognosis and functional outcome are acceptable after surgery, while patients with scores of 8-10 points, who have the shortest survival time and poorest functional outcome after surgery, appear to be best treated with radiotherapy or best supportive care.

Predicting the survival probability of gastric cancer patients developing metastatic epidural spinal cord compression (MESCC).

To create a tool for estimating the survival of gastric cancer patients developing MESCC, clinical factors were evaluated in 29 patients. Factors were age, gender, performance status, affected vertebrae, ambulatory status, further bone metastases, visceral metastases, time from gastric cancer diagnosis until MESCC and rapidity of developing weakness of legs. On multivariate analyses, visceral metastases (risk ratio: 6.80; p = 0.003) and rapidity of weakening of legs (risk ratio: 2.73; p = 0.023) had a significant effect on survival and were included in the tool. Scoring points for each of the two factors were either 0 or 1, depending on the 6-month survival rates. According to the sum of the points, three groups were built: 0 points (n = 12), 1 point (n = 10) and 2 points (n = 7). Six-month survival rates were 0, 20 and 100 % (p < 0.001). This tool for patients with MESCC from gastric cancer estimates survival probabilities, which is important for tailoring treatment to patients' needs.

Partial tumor resection combined with chemotherapy for multiple myeloma spinal cord compression.

BACKGROUND: Some controversies about the optimal therapy for multiple myeloma (MM) spinal cord compression are still presented. This study was conducted to investigate the efficacy of partial tumor resection combined with chemotherapy for MM spinal cord compression. METHODS: Eleven patients were diagnosed with MM spinal cord compression. Radiological examinations manifested 12 spinal lesions on 11 patients. All patients were treated with partial tumor resection with adjuvant chemotherapy. The mean procedure time, the mean blood loss, visual analog scale score, Oswestry Disability Index (ODI) score, neurological status, complication, recurrence, and quality of life were evaluated. RESULTS: Eleven patients were followed up with a mean of 25.1 months. The mean procedure time was 152.6 ± 30.4 min, and the mean blood loss was 396.4 ± 82.7 ml. Overall pain control rate was 89 %, with complete pain relief in 64 %, and partial pain relief in 25 %. The median pre-ODI values of 85 % significantly improved to 12 % at the last follow-up. Neurological improvement of one to two grades was observed 6 months postoperatively. Complications included pleural effusion, titanium cage loose, and thrombocytopenia in three patients each. Local recurrence was 18.2 %. One patient died of pulmonary infection. Quality of life improved from 39 % before surgery to 81 % in ten survivors at the last follow-up. CONCLUSIONS: Partial tumor resection combined with chemotherapy seems to be an effective treatment for MM spinal cord compression owing to the minor surgical trauma, fewer complications, and effective pain control. Total resection of the tumor is not necessary for MM of the spine.

Breast cancer patients with metastatic spinal cord compression. Number of extraspinal organs involved by metastases influences survival.

BACKGROUND AND PURPOSE: The goal of the present work was to investigate the predictive value of the number of extraspinal organs involved by metastases for the survival of patients with metastatic spinal cord compression (MSCC) from breast cancer. PATIENTS AND METHODS: Data of 145 breast cancer patients who received 10 fractions of 3 Gy of radiotherapy (RT) alone for MSCC were retrospectively analyzed. Seven potential prognostic factors were investigated including age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, interval from breast cancer diagnosis to RT of MSCC, ambulatory status prior to RT, time to developing motor deficits, and the number of involved extraspinal organs. RESULTS: The 1-year survival rates for involvement of 0, 1, 2, and ≥ 3 extraspinal organs were 86, 73, 36, and 16 % (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 2.19; 95 % confidence interval 1.61-3.00; p < 0.001). ECOG performance score (p < 0.001), ambulatory status prior to RT (p = 0.003), and the time to developing motor deficits (p < 0.001) were also significantly associated with survival in the multivariate analysis. CONCLUSION: The number of extraspinal organs involved by metastases is an independent prognostic factor of survival in patients with MSCC from breast cancer.

A new prognostic factor for the survival of patients with renal cell carcinoma developing metastatic spinal cord compression.

BACKGROUND AND PURPOSE: This study aimed to identify a potential association of the number of involved extraspinal organs with the survival of patients with metastatic spinal cord compression (MSCC) from renal cell carcinoma. PATIENTS AND METHODS: Data of 69 patients irradiated for MSCC from renal cell carcinoma were retrospectively evaluated for survival. The prognostic value of the number of involved extraspinal organs and eight additional factors were investigated. These additional factors included age, gender, performance status, number of involved vertebrae, interval from cancer diagnosis to radiotherapy (RT) of MSCC, ambulatory status prior to RT, time developing motor deficits, and the fractionation regimen (30 Gy in 10 fractions vs. higher doses). RESULTS: The 6-month survival rates for involvement of 0, 1, and ≥ 2 extraspinal organs were 93, 57, and 21%, respectively (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs maintained significance (risk ratio 2.65; 95% confidence interval 1.64-4.52; p < 0.001). The interval from cancer diagnosis to RT of MSCC (p = 0.013) and ambulatory status prior to RT (p = 0.002) were also independent predictors of survival. CONCLUSION: The number of involved extraspinal organs is a new prognostic factor of survival in patients with MSCC from renal cell carcinoma and should be considered in future clinical trials.

Metastatic spinal cord compression: a validated survival score for elderly patients.

BACKGROUND AND PURPOSE: This study aimed to develop a validated survival score for elderly patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: In all, 1,128 patients were randomly assigned to the test (n = 564) or validation group (n = 564). In the test group, ten pretreatment factors (age, gender, performance status, primary tumor, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time to developing motor deficits) plus the radiation regimen were retrospectively evaluated. Factors significantly associated with survival on multivariate analysis were included in the survival score. The score for each factor was determined by dividing the 6-month survival rate (%) by 10. The prognostic score represented the sum of the scores for each factor. RESULTS: In the multivariate analysis of the test group, age, performance status, primary tumor type, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time to developing motor deficits were significantly associated with survival. Total scores ranged from 25 to 57 points. In the test group, 6-month survival rates were 11 % for 25-39 points, 56 % for 40-48 points, and 97 % for 49-57 points (p < 0.001). In the validation group, 6-month survival rates were 10, 53, and 94 %, respectively (p < 0.001). CONCLUSION: Based on the survival scores of the test group, three prognostic groups were identified. The survival rates of the validation group were similar to the test group. This score appears reproducible and can help select the appropriate treatment for elderly patients with MSCC.

Bone metastases, skeletal-related events, and survival among children with cancer in Denmark.

Bone metastases and skeletal-related events (SREs), including radiation therapy or surgery to bone, pathologic fracture, or spinal cord compression, among children have not been described in a population-based study. We examined the rate of bone metastasis, SREs, and survival in the Danish pediatric cancer population. We identified children below 18 years with a first-time diagnosis of cancer between January 1, 1994 and December 31, 2009 in the Danish Cancer Registry. From the Danish National Registry of Patients, we obtained bone metastasis and SRE diagnoses, and estimated incidence rates (IRs). We estimated 6-month, 1-year, and 5-year survival using Kaplan-Meier curves. Of 2652 children, 35 (1.3%) developed bone metastasis during a mean follow-up of 7.0 years (IR=1.9 per 1000 person-years [95% confidence interval (CI), 1.4-2.6]). IRs were substantially higher among children with solid tumors than those with hematologic malignancies (IR=3.2 [95% CI, 2.3-4.6] and IR=0.48 [95% CI, 0.18-1.3]). Survival was poorer for children with bone metastasis than those without bone metastasis. Among children with bone metastasis, 67% experienced an SRE during a mean follow-up of 1.1 years, yielding an IR of 590 per 1000 person-years (95% CI, 381-915). Bone metastases are rare among children with cancer, but SREs are a common consequence.

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.

A score to identify patients with metastatic spinal cord compression who may be candidates for best supportive care.

BACKGROUND: The objective of the current study was to develop a scoring system that identifies those patients with metastatic spinal cord compression who may be candidates for best supportive care or single-fraction radiotherapy. METHODS: Ten potential prognostic factors were retrospectively analyzed in 2029 patients, including age, gender, Eastern Cooperative Oncology Group performance status, tumor type, number of involved vertebrae, further bone metastases, visceral metastases, interval from time of cancer diagnosis to the development of MSCC, time to the development of motor deficits, and ambulatory status. RESULTS: On multivariate analysis, Eastern Cooperative Oncology Group performance status, tumor type, bone metastases, visceral metastases, interval from cancer diagnosis to the development of metastatic spinal cord compression, time to the development of motor deficits, and ambulatory status were found to be significantly associated with survival. The risk score represented the sum of the scores for each of these factors, obtained from the probability of the patient dying within 2 months (shown as the percentage) divided by 10. Risk scores ranged between 6 and 25 points. At a cutoff value of ≥ 24 points, the specificity was 99.8% and the positive predictive value was 96.0%, which indicates that approximately 4% of the patients predicted to die within 2 months survived > 2 months. CONCLUSIONS: This score identifies patients who have a very poor survival with a high specificity and a high positive predictive value. Patients with a score of ≥ 24 points have a very high probability of dying within 2 months. Thus, overtreatment with intensive therapies can be avoided in these patients, who are very unlikely to benefit.

A validated scoring system to identify long-term survivors after radiotherapy for metastatic spinal cord compression.

PURPOSE: This study aimed to develop and validate a scoring system to identify long-term survivors after conventional radiotherapy (RT) for metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 1,125 patients who had received long-course RT for MSCC were included in this study. Of these patients, 344 survived for over 12 months and 781 died within a year following RT. Based on differences between the distributions of patient characteristics in the two groups, a scoring system was developed. Scores ranged from 0 to 18 points and 15 points was selected as the cutoff for identifying long-term survivors. Data from the 1,125 long-course RT patients (test group) were compared to data from 773 patients receiving short-course RT (validation group). RESULTS: A score of ≥ 15 points was associated with a 94 % proportion of long-term survivors. The 15-point cutoff resulted in a specificity of 98 % and a positive predictive value of 94 % for identification of long-term surviving patients. The proportions of long-term survivors for each scoring point in the validation group were very similar to those in the test group. CONCLUSION: This new scoring system enabled identification of long-term survivors after RT for MSCC with very high specificity and positive predictive value. The score proved to be valid and reproducible.

A validated survival score for breast cancer patients with metastatic spinal cord compression.

BACKGROUND: To create a validated scoring system predicting survival of breast cancer patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Of 510 patients, one half were assigned to either the test or the validation group. In the test group, eight pretreatment factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time of developing motor deficits) plus the radiation regimen were retrospectively investigated. Factors significantly associated with survival in the multivariate analysis were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (%) by ten. The total score was the sum of the scores for each factor. RESULTS: In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time of developing motor deficits were significant for survival and included in the score. Total scores ranged from 30 to 50 points. In the test group, the 6-month survival rates were 12% for 30-35 points, 41% for 36-40 points, 74% for 41-45 points, and 98% for 46-50 points (p < 0.0001). In the validation group, the 6-month survival rates were 14%, 46%, 77%, and 99%, respectively (p < 0.0001). CONCLUSION: The survival rates of the validation group were similar to the test group. Therefore, this score was reproducible and can help when selecting the appropriate radiotherapy regimen for each patient taking into account her survival prognosis.

Accuracy of the revised Tokuhashi score in predicting survival in patients with metastatic spinal cord compression (MSCC).

PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease. Our aim was to analyse the actual survival time of patients treated for metastatic spinal cord compression (MSCC) in comparison with the predicted survival based on the revised Tokuhashi score. This would thereby allow us to determine the overall predictive value of this scoring system. METHODS: This study was a semi-prospective clinical study of all patients with MSCC presenting to our unit over 8 years-data from October 2003 to December 2009 were collected retrospectively and from December 2009, all data collected prospectively to October 2011. Patients were divided into three groups--Group 1 (Tokuhashi score 0-8, n = 84), Group 2 (Tokuhashi score 9-11, n = 83) and Group 3 (Tokuhashi score 12-15, n = 34). Data collected included demographic data, primary tumour histology, surgery type and complications, neurological outcome (Frankel grade) and survival. RESULTS: A total of 233 patients with MSCC were managed surgically in our unit during this time. Out of these complete data were available on 201 patients for analysis. Mean age of patients was 61 years (range 18-86; 127 M, 74 F). The primary tumour type was Breast (n = 29, 15 %), Haematological (n = 28, 14 %), Renal (n = 26, 13 %), Prostate (n = 26, 13 %), Lung (n = 23, 11 %), Gastro-intestinal (n = 11, 5 %), Sarcoma (n = 9, 4 %) and others (n = 49, 24 %). All patients included in the study had surgical intervention in the form of decompression and stabilisation. Posterior decompression and stabilisation was performed in 171 patients (with vertebrectomy in 31), combined anterior and posterior approaches were used in 18 patients and 12 had an anterior approach only. The overall complication rate was 19 % (39/201)--the most common being wound infection (n = 15, 8 %). There was no difference in the neurological outcome (Frankel grade) between Groups 1 and 2 (p = 0.34) or Groups 2 and 3 (p = 0.70). However, there was a significant difference between Groups 1 and 3 (p = 0.001), with Group 3 having a significantly better neurological outcome. Median survival was 93 days in Group 1, 229 days in Group 2 and 875 days in Group 3 (p = 0.001). The predictive value between the actual and predicted survival was 64 % (Group 1), 64 % (Group 2) and 69 % (Group 3). The overall predictive value of the revised Tokuhashi score using Cox regression for all groups was 66 %. CONCLUSION: We would conclude that although the predictive value of the Tokuhashi score in terms of survival time is at best modest (66 %), the fact that there were statistically significant differences in survival between the groups looked at in this paper indicates that the scoring system, and the components which it consists of, are important in the evaluation of these patients when considering surgery.

Outcome of embolised vascular metastatic renal cell tumours causing spinal cord compression.

PURPOSE: To present the results of the surgical management of metastatic renal cell tumours of the spine with cord compression who underwent pre-operative embolisation. METHODS: We conducted a retrospective cohort study of all embolised vascular metastatic renal cell tumours of the spine that underwent urgent surgical intervention over a 7-year period (2005-2011). All medical notes, images and angiography/embolisation details were studied. We recorded the timing (immediate vs. delayed) and grade of embolisation and compared this to the estimated blood loss (EBL); extent of metastatic spinal cord compression (using the Tomita score and Bilsky scores) was also compared to EBL. Finally, neurological (Frankel grade), surgical outcome and complications were reviewed in all patients. RESULTS: During the study period, we operated on 25 emergency patients with metastatic renal cell carcinoma causing spinal cord compression who had received pre-operative embolisation (mean age 59.6 (24-78) years; 8 females, 17 males). All but one of our patients had hypervascularisation/arterio-venous fistulae on angiography. We were able to achieve greater than 90 % embolisation in the majority (17/25, 68 %) The estimated blood loss was 1,696 (400-5,000) ml; mean operating time was 276 (90-690) min and an average of 2.3 (0-7) units of whole blood was transfused. Nine patients had a posterior only decompression/stabilisation, nine patients had a posterior decompression ± cement augmentation, six had combined anterior/posterior procedures and one had anterior corpectomy/reconstruction alone. There was no statistical difference in the EBL between immediate versus delayed surgery after embolisation or the grade of embolisation. Immediate surgery after embolisation and interestingly less complete embolisation showed a trend towards less EBL. The extent of the tumour as graded by the Bilsky score correlated with increased EBL (p = 0.042). No complications occurred during the embolisation procedure. The surgical complication rate was 32 % (8/25) including two major complications (septicaemia (1) and metal work failure (2)) and five minor complications. Postoperatively, 52 % (13/25) had no change in neurological status, 36 % (9/25) improved by at least one Frankel grade and 12 % (3/25) had neurological deterioration by one Frankel grade. The average survival following surgery was 14.1 (0.5-72) months. CONCLUSION: Blood loss (mean 1,696 ml) and complications (32 %) remain a concern in the operative treatment of vascular metastatic spinal cord compression. Most patients remained the same neurologically or improved by at least 1 grade (22/25, 88 %). Paradoxically, greater embolisation showed a trend to more blood loss which could be due to more extensive surgery in this group, a rebound 'reperfusion' phenomena or even the presence of arterio-venous fistulae. Interestingly, we also found that the extent of the tumour, as graded by the Bilsky score, correlated with increased blood loss suggesting that more extensive cord compression by metastases could lead to more blood loss intra-operatively.

Surgical decompression improves recovery from neurological deficit and may provide a survival benefit in patients with diffuse large B-cell lymphoma-associated spinal cord compression: a case-series study.

BACKGROUND: Malignancy-associated spinal cord compression is generally treated by surgical decompression, radiotherapy or a combination of both. Since diffuse large B-cell lymphoma (DLBCL) is highly sensitive to both chemotherapy and radiotherapy, the role of surgical decompression in the treatment of DLBCL-associated spinal cord compression remains unclear. We therefore conducted a retrospective review to investigate the impact of surgical decompression on recovery from neurological deficit caused by DLBCL-associated spinal cord compression and patients' overall survival. METHODS: Between March 2001 and September 2011, 497 newly diagnosed DLBCL patients were reviewed, and 11 cases had DLBCL-associated spinal cord compression. Six cases were treated surgically and five cases nonsurgically. RESULTS: The rates of complete recovery from neurological deficit were 100% (6/6) and 20% (1/5) for patients in the surgical and nonsurgical groups, respectively (P = 0.015), while the median survival for patients in the surgical and nonsurgical groups was 48.6 months and 17.8 months, respectively (P = 0.177). CONCLUSIONS: We conclude that surgical decompression can improve recovery from neurological deficit in patients with DLBCL-associated spinal cord compression, possibly providing these patients a survival benefit.

Metastatic spinal cord compression in patients with cancer of unknown primary. Estimating the survival prognosis with a validated score.

BACKGROUND: This study aimed to create and validate a survival score for patients with metastatic spinal cord compression (MSCC) from cancer of unknown primary. PATIENTS AND METHODS: The entire cohort (n = 182) was divided into a test group (n = 91) and a validation group (n = 91). In the test group, eight pretreatment factors including age, gender, Eastern Cooperative Oncology Group performance status (ECOG-PS), number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, and time of developing motor deficits were retrospectively analyzed. RESULTS: The score included the prognostic factors that were significant for survival in the multivariate analysis (ECOG-PS, ambulatory status, visceral metastases, time of developing motor deficits). The score for each factor was determined by dividing the 6-month survival rate by 10. Prognostic scores represented the sum of the scores for the four factors and ranged from 5 to 20 points. The 6-month survival rates were 5% for < 14 points, 41% for 14-16 points, and 92% for > 16 points (p < 0.001). In the validation group, the 6-month survival rates were 7%, 38%, and 91% (p < 0.001). CONCLUSION: This survival score can be considered valid and reproducible, since the survival rates of the validation group were comparable to those of the test group. This score can help when selecting the individual treatment and when counseling patients and relatives.