Remineralization of lytic spinal metastases after radiation therapy - A retrospective cohort study comparing conventional external beam radiation therapy with stereotactic ablative body radiation.

Introduction: Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed. Methods: A retrospective cohort study was performed. Results: 87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 â†’ 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 â†’ 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05). Conclusion: We conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score.

Treatment of ambulatory patients with metastatic epidural spinal cord compression: a systematic review and meta-analysis.

OBJECTIVE: Approximately 10% of patients with spinal metastases develop metastatic epidural spinal cord compression (MESCC), which left undiagnosed and untreated can lead to the loss of ambulation. Timely diagnosis and efficient multidisciplinary treatment are critically important to optimize neurological outcomes. This meta-analysis aimed to determine the most efficient treatment for ambulatory patients with MESCC. METHODS: The authors conducted a systematic review and meta-analysis of the treatment of mobile patients with MESCC in terms of outcomes described as local control (LC), ambulatory function, quality of life (QOL), morbidity, and overall survival (OS). RESULTS: Overall, 54 papers (4101 patients) were included. A trend toward improved LC with stereotactic body radiotherapy (SBRT) compared with conventional external beam radiotherapy (cEBRT) was demonstrated: random effects modeling 1-year LC rate 86% (95% CI 84%-88%) versus 81% (95% CI 74%-86%) (p > 0.05), respectively, and common effects modeling 1-year LC rate 85% (95% CI 82%-87%) versus 76% (95% CI 74%-78%) (p < 0.05). Surgery followed by adjuvant radiotherapy, either cEBRT or SBRT, showed no significant benefit in either LC (OR 0.88, 95% CI 0.65-1.19) or ambulatory function (OR 1.51, 95% CI 0.83-2.74) compared with radiotherapy without surgery. There was a significant benefit of surgery compared with cEBRT regarding QOL, and furthermore SBRT alone provided long-term improvement in QOL. The type of treatment was not a significant predictor of OS, but fully ambulatory status was significantly associated with improved OS (HR 0.46-0.52, relative risk 1.79-2.3). Radiation-induced myelopathy is a rare complication of SBRT (2 patients [0.1%] in the included papers). The morbidity rate associated with surgery was relatively high, with a 10% wound complication rate and 1.6% hardware-failure rate. CONCLUSIONS: SBRT is an extremely promising treatment modality being integrated into treatment algorithms and provides durable LC. In mobile patients with MESCC, surgery does not improve LC, survival, or ambulatory function; nonetheless, there is a significant benefit of surgery in terms of QOL. In patients with MESCC without neurological deficit, the role of surgery is still debatable as studies demonstrate good LC for patients who undergo SBRT without preceding surgery. However, surgery can provide safe margins for the administration of the ablative dose of SBRT to the entire tumor volume within the constraints of spinal cord tolerance. Further randomized controlled trials are needed on the benefit of surgery before SBRT in mobile patients with MESCC. With the excellent results of separation surgery and SBRT, the role of highly invasive vertebrectomy is diminishing given the complication rate and morbidity of these procedures.

Epidemiology of spinal metastases, metastatic epidural spinal cord compression and pathologic vertebral compression fractures in patients with solid tumors: A systematic review.

Introduction: Spinal metastases (SM) are a frequent complication of cancer and may lead to pathologic vertebral compression fractures (pVCF) and/or metastatic epidural spinal cord compression (MESCC). Based on autopsy studies, it is estimated that about one third of all cancer patients will develop SM. These data may not provide a correct estimation of the incidence in clinical practice. Objective: This systematic review (SR) aims to provide a more accurate estimation of the incidence of SM, MESCC and pVCF in a clinical setting. Methods: We performed a SR of papers regarding epidemiology of SM, pVCF, and MESCC in patients with solid tumors conform PRISMA guidelines. A search was conducted in the PubMed and Web of Science database using the terms epidemiology, prevalence, incidence, global burden of disease, cost of disease, spinal metastas*, metastatic epidural spinal cord compression, pathologic fracture, vertebral compression fracture, vertebral metastas* and spinal neoplasms. Papers published between 1975 and august 2021 were included. Quality was evaluated by the STROBE criteria. Results: While 56 studies were included, none of them reports the actual definition used for MESCC and pVCF, inevitably introducing heterogenity. The overall cumulative incidence of SM and MESCC is 15.67% and 2.84% respectively in patients with a solid tumor. We calculated a mean cumulative incidence in patients with SM of 9.56% (95% CI 5.70%-13.42%) for MESCC and 12.63% (95% CI 7.00%-18.25%) for pVCF. Studies show an important delay between onset of symptoms and diagnosis. Conclusions: While the overall cumulative incidence for clinically diagnosed SM in patients with a solid tumor is 15.67%, autopsy studies reveal that SM are present in 30% by the time they die, suggesting underdiagnosing of SM. Approximately 1 out of 10 patients with SM will develop MESCC and another 12.6% will develop a pVCF. Understanding these epidemiologic data, should increase awareness for first symptoms, allowing early diagnosis and subsequent treatment, thus improving overall outcome.

Factors Influencing the Reliability of the Glasgow Coma Scale: A Systematic Review.

BACKGROUND: The Glasgow Coma Scale (GCS) characterizes patients with diminished consciousness. In a recent systematic review, we found overall adequate reliability across different clinical settings, but reliability estimates varied considerably between studies, and methodological quality of studies was overall poor. Identifying and understanding factors that can affect its reliability is important, in order to promote high standards for clinical use of the GCS. OBJECTIVE: The aim of this systematic review was to identify factors that influence reliability and to provide an evidence base for promoting consistent and reliable application of the GCS. METHODS: A comprehensive literature search was undertaken in MEDLINE, EMBASE, and CINAHL from 1974 to July 2016. Studies assessing the reliability of the GCS in adults or describing any factor that influences reliability were included. Two reviewers independently screened citations, selected full texts, and undertook data extraction and critical appraisal. Methodological quality of studies was evaluated with the consensus-based standards for the selection of health measurement instruments checklist. Data were synthesized narratively and presented in tables. RESULTS: Forty-one studies were included for analysis. Factors identified that may influence reliability are education and training, the level of consciousness, and type of stimuli used. Conflicting results were found for experience of the observer, the pathology causing the reduced consciousness, and intubation/sedation. No clear influence was found for the professional background of observers. CONCLUSION: Reliability of the GCS is influenced by multiple factors and as such is context dependent. This review points to the potential for improvement from training and education and standardization of assessment methods, for which recommendations are presented.

The reliability of the Glasgow Coma Scale: a systematic review.

INTRODUCTION: The Glasgow Coma Scale (GCS) provides a structured method for assessment of the level of consciousness. Its derived sum score is applied in research and adopted in intensive care unit scoring systems. Controversy exists on the reliability of the GCS. The aim of this systematic review was to summarize evidence on the reliability of the GCS. METHODS: A literature search was undertaken in MEDLINE, EMBASE and CINAHL. Observational studies that assessed the reliability of the GCS, expressed by a statistical measure, were included. Methodological quality was evaluated with the consensus-based standards for the selection of health measurement instruments checklist and its influence on results considered. Reliability estimates were synthesized narratively. RESULTS: We identified 52 relevant studies that showed significant heterogeneity in the type of reliability estimates used, patients studied, setting and characteristics of observers. Methodological quality was good (n = 7), fair (n = 18) or poor (n = 27). In good quality studies, kappa values were ≥0.6 in 85%, and all intraclass correlation coefficients indicated excellent reliability. Poor quality studies showed lower reliability estimates. Reliability for the GCS components was higher than for the sum score. Factors that may influence reliability include education and training, the level of consciousness and type of stimuli used. CONCLUSIONS: Only 13% of studies were of good quality and inconsistency in reported reliability estimates was found. Although the reliability was adequate in good quality studies, further improvement is desirable. From a methodological perspective, the quality of reliability studies needs to be improved. From a clinical perspective, a renewed focus on training/education and standardization of assessment is required.

Epidemiology of traumatic brain injury in Europe.

BACKGROUND: Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world, making epidemiological monitoring of incidence, prevalence and outcome of TBI necessary. We aimed to describe the epidemiology of traumatic brain injury in Europe and to evaluate the methodology of incidence studies. METHOD: We performed a systematic review and meta-analyses of articles describing the epidemiology of TBI in European countries. A search was conducted in the PubMed electronic database using the terms: epidemiology, incidence, brain injur*, head injur* and Europe. Only articles published in English and reporting on data collected in Europe between 1990 and 2014 were included. RESULTS: In total, 28 epidemiological studies on TBI from 16 European countries were identified in the literature. A great variation was found in case definitions and case ascertainment between studies. Falls and road traffic accidents (RTA) were the two most frequent causes of TBI, with falls being reported more frequently than RTA. In most of the studies a peak TBI incidence was seen in the oldest age groups. In the meta-analysis, an overall incidence rate of 262 per 100,000 for admitted TBI was derived. CONCLUSIONS: Interpretation of published epidemiologic studies is confounded by differences in inclusion criteria and case ascertainment. Nevertheless, changes in epidemiological patterns are found: falls are now the most common cause of TBI, most notably in elderly patients. Improvement of the quality of standardised data collection for TBI is mandatory for reliable monitoring of epidemiological trends and to inform appropriate targeting of prevention campaigns.