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2013 ; 17
(42
): 1-274
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gab.com Text
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English Wikipedia
A systematic review of evidence on malignant spinal metastases: natural history
and technologies for identifying patients at high risk of vertebral fracture and
spinal cord compression
#MMPMID24070110
Sutcliffe P
; Connock M
; Shyangdan D
; Court R
; Kandala NB
; Clarke A
Health Technol Assess
2013[Sep]; 17
(42
): 1-274
PMID24070110
show ga
BACKGROUND: Spinal metastases can lead to significant morbidity and reduction in
quality of life due to spinal cord compression (SCC). Between 5% and 20% of
patients with spinal metastases develop metastatic spinal cord compression during
the course of their disease. An early study estimated average survival for
patients with SCC to be between 3 and 7 months, with a 36% probability of
survival to 12 months. An understanding of the natural history and early
diagnosis of spinal metastases and prediction of collapse of the metastatic
vertebrae are important. OBJECTIVES: To undertake a systematic review to examine
the natural history of metastatic spinal lesions and to identify patients at high
risk of vertebral fracture and SCC. DATA SOURCES: The search strategy covered the
concepts of metastasis, the spine and adults. Searches were undertaken from
inception to June 2011 in 13 electronic databases [MEDLINE; MEDLINE In-Process &
Other Non-Indexed Citations; EMBASE; Cochrane Database of Systematic Reviews;
Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts
of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA
databases (NHS Centre for Reviews and Dissemination); Science Citation Index and
Conference Proceedings (Web of Science); UK Clinical Research Network (UKCRN)
Portfolio Database; Current Controlled Trials; ClinicalTrials.gov]. REVIEW
METHODS: Titles and abstracts of retrieved studies were assessed by two reviewers
independently. Disagreement was resolved by consensus agreement. Full data were
extracted independently by one reviewer. All included studies were reviewed by a
second researcher with disagreements resolved by discussion. A quality assessment
instrument was used to assess bias in six domains: study population, attrition,
prognostic factor measurement, outcome measurement, confounding measurement and
account, and analysis. Data were tabulated and discussed in a narrative review.
Each tumour type was looked at separately. RESULTS: In all, 2425 potentially
relevant articles were identified, of which 31 met the inclusion criteria. No
study examined natural history alone. Seventeen studies reported retrospective
data, 10 were prospective studies, and three were other study designs. There was
one systematic review. There were no randomised controlled trials (RCTs).
Approximately 5782 participants were included. Sample sizes ranged from 41 to
859. The age of participants ranged between 7 and 92 years. Types of cancers
reported on were lung alone (n= 3), prostate alone (n= 6), breast alone (n= 7),
mixed cancers (n= 13) and unclear (n= 1). A total of 93 prognostic factors were
identified as potentially significant in predicting risk of SCC or collapse.
Overall findings indicated that the more spinal metastases present and the longer
a patient was at risk, the greater the reported likelihood of development of SCC
and collapse. There was an increased risk of developing SCC if a cancer had
already spread to the bones. In the prostate cancer studies, tumour grade,
metastatic load and time on hormone therapy were associated with increased risk
of SCC. In one study, risk of SCC before death was 24%, and 2.37 times greater
with a Gleason score ? 7 than with a score of < 7 (p= 0.003). Other research
found that patients with six or more bone lesions were at greater risk of SCC
than those with fewer than six lesions [odds ratio (OR) 2.9, 95% confidence
interval (CI) 1.012 to 8.35, p= 0.047]. For breast cancer patients who received a
computerised tomography (CT) scan for suspected SCC, multiple logistic regression
in one study identified four independent variables predictive of a positive test:
bone metastases ? 2 years (OR 3.0 95% CI 1.2 to 7.6; p= 0.02); metastatic disease
at initial diagnosis (OR 3.4, 95% CI 1.0 to 11.4; p= 0.05); objective weakness
(OR 3.8, 95% CI 1.5 to 9.5; p= 0.005); and vertebral compression fracture on
spine radiograph (OR 2.6, 95% CI 1.0 to 6.5; p= 0.05). A further study on mixed
cancers, among patients who received surgery for SCC, reported that vertebral
body compression fractures were associated with presurgery chemotherapy (OR
2.283, 95% CI 1.064 to 4.898; p= 0.03), cancer type [primary breast cancer (OR
4.179, 95% CI 1.457 to 11.983; p= 0.008)], thoracic involvement (OR 3.505, 95% CI
1.343 to 9.143; p= 0.01) and anterior cord compression (OR 3.213, 95% CI 1.416 to
7.293; p= 0.005). LIMITATIONS: Many of the included studies provided limited
information about patient populations and selection criteria and they varied in
methodological quality, rigour and transparency. Several studies identified type
of cancer (e.g. breast, lung or prostate cancer) as a significant factor in
predicting SCC, but it remains difficult to determine the risk differential
partly because of residual bias. Consideration of quantitative results from the
studies does not easily allow generation of a coherent numerical summary, studies
were heterogeneous especially with regard to population, results were not
consistent between studies, and study results almost universally lacked
corroboration from other independent studies. CONCLUSION: No studies were found
which examined natural history. Overall burden of metastatic disease, confirmed
metastatic bone involvement and immediate symptomatology suggestive of spinal
column involvement are already well known as factors for metastatic SCC,
vertebral collapse or progression of vertebral collapse. Although we identified a
large number of additional possible prognostic factors, those which currently
offer the most potential are unclear. Current clinical consensus favours magnetic
resonance imaging and CT imaging modalities for the investigation of SCC and
vertebral fracture. Future research should concentrate on: (1) prospective
randomised designs to establish clinical and quality-of-life outcomes and
cost-effectiveness of identification and treatment of patients at high risk of
vertebral collapse and SCC; (2) Service Delivery and Organisation research on
magnetic resonance imaging (MRI) scans and scanning (in tandem with research
studies on use of MRI to monitor progression) in order to understand best methods
for maximising use of MRI scanners; and (3) investigation of prognostic
algorithms to calculate probability of a specified event using high-quality
prospective studies, involving defined populations, randomly selected and clearly
identified samples, and with blinding of investigators. FUNDING: This report was
commissioned by the National Institute for Health Research Health Technology
Assessment Programme NIHR HTA Programme as project number HTA 10/91/01.
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