Evidence reviews for investigations – diagnosis

Evidence reviews for investigations – diagnosis

Spinal metastases and metastatic spinal cord compression

Evidence review F

NICE Guideline, No. 234

London: National Institute for Health and Care Excellence (NICE); 2023 Sep.

ISBN-13: 978-1-4731-5316-5

Investigations - diagnosis

Review question

How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Introduction

The diagnosis of metastatic spinal cord compression or spinal metastases typically requires radiological imaging. Clinical signs may be the same for malignant and benign spinal disease in people with known primary cancer. Some people without known primary cancer present with spinal cord compression as their first symptom. MRI has been the method of choice for investigating malignant spinal disease and cord compression, due to its ability to identify metastatic disease within bone, visualise the soft tissue component of lesions and show the degree of any cord compression. Computed tomography (CT) and fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) also potentially provide additional information. This review aimed to summarise the effectiveness of different radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression.

Summary of the protocol

See Table 1 for a summary of the Population, Index test, Reference standard (or Comparator), Target condition and Outcome (PIRTO) characteristics of this review.

Table 1

Summary of the protocol (PIRTO table).

For further details see the review protocol in appendix A.

Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document (supplementary document 1).

Declarations of interest were recorded according to NICE’s conflicts of interest policy.

Diagnostic evidence

Included studies

Twenty studies were included in this evidence review, 1 randomised trial (Dearnaley 2022), 1 observational study (Allan 2009), 3 systematic reviews (Kim 2020, Li 2019, Suh 2018) and 15 diagnostic accuracy studies (Bacher 2021, Husband 2001, Kato 2015, Kim 2000, Laufer 2009, Maeder 2018, Perry 2018, Phadke 2001, Razek 2019, Schmeel 2018, Schmeel 2021, Shi 2017, Spinnato 2018, Taheri 2017, Zafar 2020).

Test and treat studies

One test-and-treat RCT (Dearnaley 2022) compared screening MRI with no screening MRI in men at high risk of malignant spinal cord compression.

One study (Allan 2009) compared a rapid MRI referral hotline for suspected malignant spinal cord compression with usual care.

Diagnostic test accuracy studies

One systematic review (Suh 2018) and 5 additional studies (Maeder 2018, Perry 2018, Schmeel 2021, Shi 2017, Taheri 2017) evaluated chemical shift MRI for the differential diagnosis of malignant and non-malignant bone marrow lesions.

Two systematic reviews (Li 2019, Suh 2018) and 2 additional studies (Bacher 2021, Schmeel 2018) evaluated chemical shift MRI for the differential diagnosis of malignant and non-malignant vertebral compression fractures.

One systematic review (Li 2019) and 3 additional studies (Kato 2015, Razek 2019, Zafar 2020) evaluated conventional MRI sequences, contrast enhanced MRI and diffusion weighted imaging for the differential diagnosis of malignant and non-malignant vertebral compression fractures.

One systematic review (Kim 2020) evaluated FDG-PET-CT or FDG-PET for the differential diagnosis of malignant and non-malignant vertebral compression fractures.

One study (Husband 2001) evaluated plain radiographs and neurology for the diagnosis of malignant spinal cord compression and for the impact of MRI on treatment planning.

One study (Kim 2000) reported the diagnostic accuracy of T1-weighted sagittal images alone for the for the diagnosis of malignant spinal cord compression.

Three studies (Laufer 2009, Phadke 2001, Spinnato 2018) reported the diagnostic yield of CT-guided biopsy of suspected malignant spinal lesions.

The included studies are summarised in Table 2.

See the literature search strategy in appendix B and study selection flow chart in appendix C.

Excluded studies

Studies not included in this review are listed, and reasons for their exclusion are provided in appendix K.

Summary of included studies

Summaries of the studies that were included in this review are presented in Table 2.

Table 2

Summary of included studies.

See the full evidence tables in appendix D, the forest plots in appendix E and the study data in appendix L.

Summary of the evidence

Screening MRI verses no screening MRI

Evidence from a randomised trial indicated that screening using spinal MRI for people at high risk of metastatic spinal cord compression made no important difference to overall survival. There was also no evidence of important difference in neurological and functional status, pain or quality of life. The evidence quality ranged from low to high.

MSCC hotline verses usual care

Evidence from an observational study showed a benefit of a telephone hotline compared to usual care because it enabled rapid referral and diagnosis of patients with suspected MSCC. Median time from referral to diagnosis was 2 weeks shorter in the telephone hotline group compared to usual care. Patients referred via the hotline were also more likely to be ambulant at the time of diagnosis. The evidence quality ranged from very low to low.

Chemical shift MRI for the differential diagnosis of malignant and non-malignant vertebral bone marrow lesions

Chemical shift MRI had acceptable (>80%) sensitivity and specificity in the differential diagnosis of malignant and non-malignant vertebral bone marrow lesions (BML). Likelihood ratios indicated that chemical shift MRI is a useful test in this context (positive likelihood ratio [LR+] > 5 and negative likelihood ratio [LR−] < 0.2). The evidence quality for this was moderate to high.

FDG-PET for the differential diagnosis of malignant and non-malignant vertebral compression fractures

FDG-PET or FDG-PET-CT had acceptable (>80%) sensitivity for the differential diagnosis of malignant and non-malignant VCF, but somewhat lower specificity suggesting false positives would be an issue with this imaging modality. Likelihood ratios indicated that FDG-PET or FDG-PET-CT was potentially a useful test (LR+ between 2 and 5, LR− <0.2) again indicating some uncertainty in positive test results. The evidence quality for this was low.

Chemical shift MRI for the differential diagnosis of malignant and non-malignant vertebral compression fractures

Chemical shift MRI had acceptable (>80%) sensitivity and specificity for differential diagnosis of malignant and non-malignant vertebral compression fractures (VCF). Likelihood ratios indicated that chemical shift MRI is a useful test in this context (LR+ > 5, LR− < 0.2). The evidence quality for this was moderate to high.

Conventional MRI sequences(with or without DWI) for the differential diagnosis of malignant and non-malignant vertebral compression fractures

Conventional MRI sequences with or without diffusion weighted imaging or contrast enhancement had acceptable sensitivity and specificity for differential diagnosis of VCF. Likelihood ratios indicated that conventional MRI sequences with diffusion weighted imaging is a useful test in this context (LR+ > 5, LR− < 0.2). The evidence quality for this was moderate. Likelihood ratios indicated that conventional MRI sequences are a useful test in this context (LR+ > 5, LR− < 0.2). The evidence quality for this was very low to moderate.

Tests for diagnosis of metastatic spinal cord compression

Evidence for imaging diagnosis of spinal cord compression was more limited. One study indicated that T1-weighted sagittal MRI images alone had relatively low sensitivity but high specificity for spinal cord compression. Likelihood ratios indicated this was potentially a useful test (LR+ > 5, LR− between 0.2 and 0.5). Another observational study found that plain radiographs plus neurological examination had very low sensitivity but high specificity for spinal cord compression. The likelihood ratios indicated plain radiographs plus neurological examination was unlikely to be a useful test for metastatic spinal cord compression (LR+ > 5, LR− > 0.5). The evidence quality for this was low.

Very low quality evidence suggested that CT-guided biopsies of suspected metastatic spinal lesions do not always provide sufficient material for diagnosis. There was uncertainty, however, about how often this occurs with reported diagnostic yields ranging from 81% to 99% in the included studies.

See appendix F for GRADE and modified GRADE tables.

Economic evidence

Included studies

A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.

A single economic search was undertaken for all topics included in the scope of this guideline. See supplement 2 for details.

Excluded studies

Economic studies not included in this review are listed, and reasons for their exclusion are provided in supplement 2.

No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.

The committee's discussion and interpretation of the evidence

The outcomes that matter most

Critical outcomes were overall survival, disease related morbidity, neurological/functional status and quality of life. This was because prompt and accurate diagnosis should lead to appropriate treatment, avoiding the morbidity caused by spinal cord compression and potentially prolonging life. For this reason, diagnostic accuracy was also a critical outcome.

Pain was an important outcome because it is a common symptom of metastatic spinal disease with negative impact on quality of life. Time to treatment was an important outcome because diagnostic uncertainty can delay treatment. Also, referral for specialist tests or dealing with equivocal test results can cause treatment delays. False positive test results can have important consequences in this group, leading to unnecessary treatment or biopsy. Morbidity caused by biopsy was included as an important outcome for this reason. Finally test failure was included as an important outcome, because sometimes diagnostic tests do not produce a clear positive or negative result, leading to uncertainty, repeated tests and diagnostic delays.

The quality of the evidence

The quality of the evidence rated using GRADE ranged from low to high. The main issues that lowered the quality of the outcomes were risk of bias and imprecision.

No evidence was identified relating to CT scans or for the outcomes of disease-related morbidity, pain, consequences of false positives and morbidity due to biopsy.

Benefits and harms

Radiologist involvement

Based on their knowledge and experience the committee noted that carrying out radiological imagining of the spine and interpreting the results is complex (for example, selecting the correct sequencing and, if necessary, supplementary axial imaging) and that the impact of errors may have very serious consequences. In their experience there is also variation in how urgently results are reported, which can affect starting timely treatment. The committee agreed that imaging should be overseen by a radiologist. It was discussed that having a radiologist present at all MRI imaging appointments for MSCC would be difficult because of the urgency in which they would need to be conducted. They noted that it is now possible that scans can be overseen virtually which means that a radiologist would not necessarily need to be there in person but could oversee it remotely. Having a radiologist there also means that they can interpret and report the findings promptly.

The committee discussed the evidence showing an important benefit of a telephone hotline compared to usual care. They noted that it enabled rapid referral and diagnosis of patients with suspected MSCC. They agreed that any pathway to urgent MRI is useful and there are service configurations that work in some areas but not others. However, they decided not to recommend a hotline for MRI because they did not want to be prescriptive about how services organise their MRI lists to provide urgent access. They acknowledged that this is addressed in another part of the guideline that is focused on service configuration to support urgent MRI diagnosis of MSCC (see evidence review A).

MRI assessment

Based on the evidence and their experience the committee agreed that conventional MRI sequences (including T1-weighted imaging, T2-weighted imaging and short TI inversion recovery (STIR) sequences) have acceptable sensitivity and specificity (considerably higher than the committee’s decision threshold of 80%) for identifying metastatic disease within bone when the correct sequences are used, and they listed the appropriate sequences in their recommendation. Sagittal T1 and/or STIR sequences of the whole spine would be used identify spinal metastases. Whereas sagittal T2 weighted sequences (with supplementary axial imaging) can also show any soft tissue component of the mass and the degree of spinal cord compression.

The committee discussed the evidence on adding contrast-enhanced MRI, diffusion weighted imaging or chemical shift MRI to conventional sequences which may have a role in differentiating normal versus malignant bone marrow or osteoporotic versus malignant compression fractures. They were not convinced the evidence supported routinely adding these additional sequences to conventional MRI because the main role of MRI in this context is to identify the presence or absence of metastases and involvement of the spinal cord, rather than differentiate benign verses malignant lesions or fractures, however they understood that these additional sequences may be useful in selected cases and that local protocols or guidelines would be typically in place for their use.

They recommended not to perform routine MRI in people without symptoms or signs of cord compression in order to screen for MSCC, because evidence from a randomised trial did not demonstrate any benefit of surveillance MRIs in people who are asymptomatic but are at high risk of MSCC.

Other imaging techniques for diagnosis and management

Although there was no evidence about the use of CT in diagnosis of metastatic spinal disease the committee acknowledged that MRI might be contraindicated in some people (for instance anyone with metal implants). They considered CT was an appropriate alternative (although less sensitive than modern MRI) for imaging the spine in these cases and widely used for cancer staging. They acknowledged, based on experience that in rare cases there may be an indication for CT myelography, but this would need to be done in a specialist centre because it is an invasive procedure which is associated with some risks.

The committee discussed that many patients presenting with symptoms of spinal metastases or cord compression may have already had plain X-rays as initial investigations, but they agreed based on their experience that plain X-rays were not as sensitive for detecting metastatic bone disease as MRI and recommended they should not be used to diagnose or rule out spinal metastases, direct malignant infiltration (DMI) of the spine or MSCC. There was also evidence that X-rays and neurological examination would detect less than half of the cases of spinal cord compression which can accompany spinal metastases.

The committee noted the evidence showing that CT-guided biopsies of suspected metastatic spinal lesions do not always provide sufficient material for diagnosis. However, they decided that due to the very low quality there was too much uncertainty about this evidence to base a recommendation on.

Cost effectiveness and resource use

No economic evidence was identified for this topic from the systematic search of previously published evidence. The committee considered cost effectiveness based on their own experience and knowledge.

Recommendations for this topic will lead to cost savings with no or limited impact on outcomes for people receiving these healthcare services. Whilst imaging being overseen by a radiologist would take up their time and associated costs the consequences of missing important details would be serious which would accrue larger costs in the long term. Recommendations against routine MRI in people without symptoms or signs of MSCC should reduce the number of MRIs undertaken although only a handful of centres are currently performing MRI in these circumstances. RCT evidence suggests this will have no impact upon outcomes or quality of life for patients.

Recommendations against x-ray, although a less expensive imaging technique should reduce costs as the diagnostic utility of them is very limited and MRI diagnostic imaging would always have to be carried out to get sufficiently detailed information to locate the tumour and plan treatment.

Recommendations supported by this evidence review

This evidence review supports recommendations 1.5.1 and 1.5.5 to 1.5.9 in the NICE guideline.

References – included studies

Diagnostic

Allan 2009
Allan L, Baker L, Dewar J, et al Suspected malignant cord compression – Improving time to diagnosis via a hotline: A prospective audit. British Journal of Cancer, 100, 1867–1872, 2009 [PMC free article: PMC2714247] [PubMed: 19471276]
Bacher 2021
Bacher S, Hajdu S, Maeder Y, et al Differentiation between benign and malignant vertebral compression fractures using qualitative and quantitative analysis of a single fast spin echo T2-weighted Dixon sequence. European Radiology, 31, 9418–942, 2021 [PMC free article: PMC8589814] [PubMed: 34041569]
Dearnaley 2022
Dearnaley D, Hinder V, Hijab A, et al Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration-resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial. Lancet: Oncology, 23, 501–513, 2022 [PMC free article: PMC8960282] [PubMed: 35279270]
Husband 2001
Husband D, Grant K, Romaniuk C. MRI in the diagnosis and treatment of suspected malignant spinal cord compression. British Journal of Radiology 74, 15–23, 2001 [PubMed: 11227772]
Kato 2015
Kato S, Hozumi T, Yamakawa K, et al META: an MRI-based scoring system differentiating metastatic from osteoporotic vertebral fractures. Spine Journal, 15, 1563–70, 2015 [PubMed: 25777741]
Kim 2000
Kim J, Learch T, Colletti P, et al Diagnosis of vertebral metastasis, epidural metastasis, and malignant spinal cord compression: are T(1)-weighted sagittal images sufficient? Magnetic Resonance Imaging 18, 819–24, 2000 [PubMed: 11027875]
Kim 2020
Kim S, Lee J. (2020) Diagnostic performance of F-18 FDG PET or PET/CT for differentiation of benign from malignant vertebral compression fractures; A meta-analysis. World Neurosurgery, 137: e626–e633, 2020 [PubMed: 32105873]
Laufer 2009
Laufer I, Lis E, Pisinski L, et al The accuracy of [(18) F] fluorodeoxyglucose positron emission tomography as confirmed by biopsy in the diagnosis of spine metastases in a cancer population. Neurosurgery, 64, 107–4, 2009 [PubMed: 19145159]
Li 2019
Li K, Huang L, Lang Z, et al Reliability and Validity of Different MRI Sequences in Improving the Accuracy of Differential Diagnosis of Benign and Malignant Vertebral Fractures: A Meta-Analysis. American Journal of Roentgenology, 213, 427–436, 2019 [PubMed: 31039028]
Maeder 2018
Maeder Y, Dunet V, Richard R, et al Bone Marrow Metastases: T2-weighted Dixon Spin-Echo Fat Images Can Replace T1-weighted Spin-Echo Images. Radiology, 286, 948–959, 2018 [PubMed: 29095674]
Perry 2018
Perry M, and Sebro R. Accuracy of Opposed-phase Magnetic Resonance Imaging for the Evaluation of Treated and Untreated Spinal Metastases. Academic Radiology, 25, 877–882, 2018 [PubMed: 29398437]
Phadke 2001
Phadke D, Lucas D, Madan S. Fine-needle aspiration biopsy of vertebral and intervertebral disc lesions: specimen adequacy, diagnostic utility, and pitfalls. Archives of Pathology and Laboratory Medicine, 125, 1463–8, 2001 [PubMed: 11698003]
Razek 2009
Razek A, Sherif F. Diagnostic accuracy of diffusion tensor imaging in differentiating malignant from benign compressed vertebrae. Neuroradiology, 61, 1291–1296, 2019 [PubMed: 31492969]
Schmeel 2018
Schmeel F, Luetkens J, Feist A, et al Quantitative evaluation of T2* relaxation times for the differentiation of acute benign and malignant vertebral body fractures. European Journal of Radiology, 108, 59–65, 2018 [PubMed: 30396672]
Schmeel 2021
Schmeel F, Enkirch S, Luetkens J, et al Diagnostic Accuracy of Quantitative Imaging Biomarkers in the Differentiation of Benign and Malignant Vertebral Lesions: Combination of Diffusion-Weighted and Proton Density Fat Fraction Spine MRI. Clinical Neuroradiology, 31, 1059–1070, 2021 [PMC free article: PMC8648653] [PubMed: 33787957]
Shi 2017
Shi Y, Li X, Zhang X, et al Differential diagnosis of hemangiomas from spinal osteolytic metastases using 3.0 T MRI: comparison of T1-weighted imaging, chemical-shift imaging, diffusion-weighted and contrast-enhanced imaging. Oncotarget, 8, 71095–71104, 2017 [PMC free article: PMC5642620] [PubMed: 29050345]
Spinnato 2018
Spinnato P, Bazzocchi A, Facchini G, et al Vertebral Fractures of Unknown Origin: Role of Computed Tomography-Guided Biopsy. International Journal of Spine Surgery, 12, 673–679, 2018 [PMC free article: PMC6314342] [PubMed: 30619670]
Suh 2018
Suh C, Yun S, Jin W, et al Diagnostic Performance of In-Phase and Opposed-Phase Chemical-Shift Imaging for Differentiating Benign and Malignant Vertebral Marrow Lesions: A Meta-Analysis. American Journal of Roentgenology 211, W1–W10, 2018 [PubMed: 30160981]
Taheri 2017
Taheri M, Mirzaei H, Shahhamzei S, et al Comparison of chemical shift MR imaging findings between vertebral benign and metastatic lesions. International Journal of Cancer Management 10, e8661, 2017
Zafar 2020
Zafar U, Malik A, Shahzad I, et al Diagnostic accuracy of qualitative diffusion weighted MRI of spine in differentiating between benign and malignant vertebral fractures taking histopathology as gold standard. Pakistan Journal of Medical and Health Sciences 14, 390–392, 2020

Appendices

Appendix G. Economic evidence study selection

Study selection for: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

No economic evidence was identified which was applicable to this review question.

Appendix H. Economic evidence tables

Economic evidence tables for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

No evidence was identified which was applicable to this review question.

Appendix I. Economic model

Economic model for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

No economic analysis was conducted for this review question.

Appendix J. Excluded studies

Excluded studies for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Excluded diagnostic studies

Table 10

Excluded studies and reasons for their exclusion.

Excluded economic studies

No economic evidence was identified for this review. See supplement 2 for further information.

Appendix K. Research recommendations – full details

Research recommendations for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

No research recommendations were made for this review question.

Appendix L. Study data - diagnostic accuracy

Diagnostic accuracy data for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression? (PDF, 166K)

Final version

Evidence reviews underpinning recommendations 1.5.1, 1.5.5 to 1.5.9 in the NICE guideline

These evidence reviews were developed by NICE

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK602764PMID: 38635795

Table 1Summary of the protocol (PIRTO table)

Population	Adults with suspected or confirmed metastatic spinal disease direct malignant infiltration of the spine. Adults with suspected or confirmed spinal cord or nerve root compression because of metastatic spinal disease direct malignant infiltration of the spine
Index test	For diagnosis of spinal metastasis / direct infiltration: MRI T1 sequences (with/without contrast) short T1 inversion recovery (STIR) sequences T2 weighted sequences (to show the level and degree of compression of the cord / lesions within cord) Whole spine imaging CT (whole spine or other) Image guided biopsy (for example for solitary metastasis) Plain X-ray FDG-PET-CT
Reference standard (or comparator)	For test and treat studies comparisons are: Routine imaging versus sign/symptom directed Delayed versus early imaging Different test sequences in comparison with each other For diagnostic accuracy studies reference standard is: Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done)
Target condition	Metastatic spinal disease Direct malignant infiltration of the spine Spinal cord compression associated with the above
Outcomes	Critical For test and treat studies: Overall survival Disease-related morbidity Neurological/functional status Quality of life For diagnostic accuracy studies: Sensitivity, specificity Likelihood ratios PPV, NPV Important Pain Time to treatment Test-related morbidity, for example: Consequences of false positives Morbidity due to biopsy Test failure (incomplete or cancelled test – for example due to anxiety or claustrophobia during MRI)

: CT: computed tomography; FDG-PET-CT: fluorodeoxyglucose-positron emission tomography-computed tomography; MRI: magnetic resonance imaging; NPV: negative predictive value; PPV: positive predictive value.

Table 2Summary of included studies.

Study	Population	Index test or intervention	Reference standard or comparison	Target condition	Outcomes
Allan 2009 Retrospective cohort study UK	N=424 Patients with suspected malignant spinal cord compression referred via hotline Patients with malignant spinal cord compression (Clinical Research and Audit group) Age and sex not reported.	Telephone hotline group (quick access to MRI)	Control group (diagnosis following usual care)	MSCC	Neurological and functional status: Number of patients walking at time of diagnosis Time to treatment: Time from referral to diagnosis of MSCC
Bacher 2021 Retrospective cohort study Switzerland	N=95 Consecutive patients undergoing spine MRI (at a single institution) prior to cementoplasty for acute vertebral compression fractures. Age, mean, years (SD): 76 (l2) for those with benign lesions 63 (12) for those with malignant lesions	MRI - single sagittal fast spin echo T2-weighted Dixon sequence	Radiological follow-up (radiographs, CT, MRI, bone scans and PET-CT studies) and biopsy results, follow-up 9 months	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Dearnley 2022 RCT UK	N=410 Patients with metastatic castration resistant prostate cancer with bone involvement. Age: (median, IQR) MRI group: 74.3 (68.0–79.3) Control group: 74.2 (68.5–79.3) Sex: male n=410	Screening spinal MRI	No screening MRI	MSCC	Overall survival Neurological and functional status Quality of life Pain
Husband 2001 Prospective cohort study UK	N=280 Consecutive patients with suspected spinal cord compression undergoing MRI. Age, median, years (range): 67 (23 – 89) Sex: female n=122; male n=158.	Plain radiograph and neurological examination	Radiological follow-up (MRI carried out as soon as possible usually the next day)	MSCC	Accuracy of the X-ray plus neurological examination diagnosis: Sensitivity/ specificity Likelihood ratios PPV, NPV
Kato 2015 Retrospective cohort study Japan	N=200 Patients with radiologically apparent collapse of thoracolumbar vertebra due to metastatic vertebral compression fractures or osteoporotic vertebral fractures. Age, mean, years (SD): people with osteoporotic fractures 73 (11) people with metastatic fractures 64 (11) Sex: female n=130; male n=70.	MRI	Biopsy result / surgical pathology Clinical and radiological follow up of 60 days (if no surgery/biopsy done)	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Kim 2000 Retrospective cohort study USA	N=57 Consecutive patients undergoing MRI for clinically suspected malignant spinal cord compression. Age, median, years (range): 49 (22 – 87). Sex: female n=26; male n=31.	MRI - T1-weighted sagittal images only	MRI – complete imaging studies of spinal column (T1 and T2 weighted sagittal images; and T1 and/or T2 weighted axial images. Based on agreement in diagnosis between 3 radiologists on examination of complete imaging study for each patient.	MSCC	Accuracy of the MRI diagnosis for different spinal metastases or MSCC divided according to external and internal standard : Sensitivity/specificity Likelihood ratios
Kim 2020 Systematic review of diagnostic accuracy studies	N=274 (in 5 studies) Patients with vertebral compression fractures Age, mean years: range 60 to 72. SD not reported Sex: female n=92; male n=182.	FDG-PET FDG-PET/CT	Composite reference standard of biopsy, clinical follow-up and repeat imaging	Malignant VCF	Accuracy of the FDG-PET or FDG PET/CT diagnosis: Sensitivity/specificity Likelihood ratios
Laufer 2009 Retrospective cohort study USA	N=82 Patients with a previous diagnosis of cancer undergoing CT-guided biopsy of suspected malignant spinal column lesion. Age, mean, years (SD): 56. SD not reported. Sex: female n=49; male n=41.	FDG-PET	CT guided biopsy	Malignant spinal column lesions	Test failure/success diagnostic yield of biopsy
Li 2019 Systematic review of diagnostic accuracy studies	N=895 Patients with vertebral fractures Age: mean ranged from 54.6 to 69 years across the studies Sex: female n=486; male n=409.	MRI chemical shift imaging MRI conventional sequences plus diffusion weighted imaging MRI conventional sequences MRI conventional sequences plus contrast enhanced images	Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done)	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Maeder 2018 Retrospective cohort study Switzerland	N=121 Consecutive patients undergoing whole spine MRI for suspected vertebral metastases. Age, mean, years (SD): 61.4 (11.8). Sex: female n=58; male n=63.	MRI – sagittal SE Dixon T2-weighted fat-only and water-only imaging. MRI – sagittal SE T1-weighted and SE Dixon T2-weighted water-only images.	Biopsy result / surgical pathology Clinical and radiological follow up of at least 8 months	Malignant BML	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Perry 2018 Retrospective cohort study USA	N=101 Patients undergoing opposed-phase MRI of the cervical, thoracic, or lumbar spine. Age, mean, years (SD): 57.7 (14.1). Sex: female n=62; male n=39.	Opposed phase MRI	Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done) up to 2 years	Malignant BML	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Phadke 2001 Retrospective cohort study USA	N=78 Patients undergoing CT guided fine needle aspiration biopsy for vertebral and intervertebral lesions (included patients without a known malignancy). Age: not reported. Sex: female n=49; male n=29.	CT guided fine needle aspiration biopsy	Cytopathologist’s assessment of sample adequacy and diagnosis (if sample was adequate)	Malignant spinal lesions	Test failure/success diagnostic yield of biopsy
Razek 2019 Retrospective cohort study Egypt	N=45 Patients with untreated compressed vertebrae undergoing MRI. Age, mean, years (SD): 56.14 (7.9). Sex: female n=22; male n=22.	MRI – T1 and T2 weighted and DTI	Biopsy result / surgical pathology	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Schmeel 2018 Retrospective cohort study Germany	N=37 Consecutive patients with a suspected acute vertebral compression fracture or known primary malignancy and suspected pathological vertebral compression fracture. Age, mean, years (SD): 64.8 (16.5). Sex: female n=20; male n=17.	MRI – T2-weighted.	Biopsy result / surgical pathology	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Schmeel 2021 Prospective cohort study Germany	N=55 Consecutive patients with untreated vertebral bone marrow lesions undergoing MRI. Age, mean, years (SD): 68 (14). Sex: female n=30; male n=25.	MRI - sagittal DWI and CSE-based MRI in addition to routine clinical spine MRI and chemical shift imaging	Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done) of at least 6 months	Malignant BML	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Shi 2017 Retrospective cohort study China	N=53 Consecutive patients with spinal haemangiomas Consecutive patients with spinal metastases Age, mean, years (SD): 60.62 (8.23). Sex: female n=11; male n=16.	MRI – T1-weighted imaging with and without fat suppression, chemical shift imaging, DWI, and enhanced imaging at 3.0 T MRI.	Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done) of at least 6 months	Malignant BML	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Spinnato 2018 Retrospective cohort study Italy	N=32 Patients with 1 or more non-traumatic vertebral fracture of unknown aetiology. Age, mean, years (SD): 57.1 (23.3). Sex: female n=19; male n=13.	CT guided biopsy	Histopathologist’s assessment of sample adequacy and diagnosis	Malignant spinal lesions	Test failure/success diagnostic yield of biopsy
Suh 2018 Systematic review of diagnostic accuracy studies	N=591 Patients with vertebral bone marrow lesions undergoing MRI Age: ranged from 45 to 68 across studies Sex: female n=293; male n=277 (where reported).	MRI chemical shift imaging	Biopsy result / surgical pathology Clinical or radiological follow-up (range 1 to 20 months)	Malignant BML malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Taheri 2017 Prospective cohort study Iran	N=51 Patients with vertebral focal lesions referred for routine MRI of the spine. Age, mean, years (SD): 52.61 (13.52). Sex: female n=23; male n=28.	MRI – dual-phase chemical shift imaging	Biopsy result / surgical pathology Clinical and radiological follow up (if no surgery/biopsy done)	Malignant BML	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV
Zafar 2020 Prospective cohort study Pakistan	N=280 Patients with vertebral fractures on digital x ray of spine showing decreased vertebral body height, reduced disc intervertebral disc space or collapsed vertebra Age, mean, years (SD): 42.61 (11.79). Sex: female n=124; male n=156.	MRI – Plain and DWI.	Biopsy result / surgical pathology	Malignant VCF	Accuracy of the MRI diagnosis: Sensitivity/specificity Likelihood ratios PPV, NPV

: BML: bone marrow lesions; CT: computed tomography; DTI: diffusion-tensor imaging; DWI: diffusion weighted imaging; FDG-PET: fluorodeoxyglucose positron emission tomography; MRI: magnetic resonance imaging; MSCC: metastatic spinal cord compression; NPV: negative predictive value; PPV, positive predictive value; RCT: randomised controlled trial; SD: standard deviation; VCF: vertebral compression fractures

Table 10Excluded studies and reasons for their exclusion

Study	Exclusion reason
Abdel-Wanis, M E; Solyman, Mohamed Tharwat Mahmoud; Hasan, Nahla Mohamed Ali (2011) Sensitivity, specificity and accuracy of magnetic resonance imaging for differentiating vertebral compression fractures caused by malignancy, osteoporosis, and infections. Journal of orthopaedic surgery (Hong Kong) 19(2): 145–50 [PubMed: 21857034]	Outcomes do not match review protocol
Abdullayev, N, Grose Hokamp, N, Lennartz, S et al (2019) Improvements of diagnostic accuracy and visualization of vertebral metastasis using multi-level virtual non-calcium reconstructions from dual-layer spectral detector computed tomography. European radiology 29(11): 5941–5949 [PubMed: 31041562]	Index test - does not match review protocol
Abedi, S.M.; Mardanshahi, A.; Zeanali, R. (2021) Added diagnostic value of SPECT to evaluate bone metastases in breast cancer patients with normal whole body bone scan. Caspian Journal of Internal Medicine 12(3): 290–293 [PMC free article: PMC8223046] [PubMed: 34221278]	Population - does not match review protocol
Abikhzer, G., Srour, S., Fried, G. et al (2016) Prospective comparison of whole-body bone SPECT and sodium 18F-fluoride PET in the detection of bone metastases from breast cancer. Nuclear Medicine Communications 37(11): 1160–1168 [PubMed: 27536906]	Population - does not match review protocol
Abrahm, J.L. (2004) Assessment and treatment of patients with malignant spinal cord compression. Journal of Supportive Oncology 2(5): 377–391 [PubMed: 15524067]	Study design - does not match review protocol
Adamova, Blanka, Bednarik, Josef, Andrasinova, Tereza et al (2015) Does lumbar spinal stenosis increase the risk of spondylotic cervical spinal cord compression? 24(12): 2946–53 [PubMed: 26038157]	Population - does not match review protocol
Adams, S, Baum, R P, Stuckensen, T et al (1998) Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. European journal of nuclear medicine 25(9): 1255–60 [PubMed: 9724374]	Population - does not match review protocol
Adogwa, Owoicho, Rubio, Daniel R, Buchowski, Jacob M et al (2022) Spine-specific skeletal related events and mortality in non-small cell lung cancer patients: a single-institution analysis. Journal of neurosurgery. Spine 36(1): 125–132 [PubMed: 33254136]	Index test - does not match review protocol
Aggarwal, Ashish, Salunke, Pravin, Shekhar, Bala Raja et al (2013) The role of magnetic resonance imaging and positron emission tomography-computed tomography combined in differentiating benign from malignant lesions contributing to vertebral compression fractures. Surgical neurology international 4(suppl5): 323–6 [PMC free article: PMC3717528] [PubMed: 23878766]	Other protocol criteria - study reported in an included systematic review (Kim 2020)
Ahn, Ji Eun, Lee, Jeong Hyun, Yi, Jong Sook et al (2008) Diagnostic accuracy of CT and ultrasonography for evaluating metastatic cervical lymph nodes in patients with thyroid cancer. World journal of surgery 32(7): 1552–8 [PubMed: 18408961]	Population - does not match review protocol
Algra, P R, Bloem, J L, Tissing, H et al (1991) Detection of vertebral metastases: comparison between MR imaging and bone scintigraphy. Radiographics: a review publication of the Radiological Society of North America, Inc 11(2): 219–32 [PubMed: 2028061]	Outcomes - do not match review protocol
Alkalay, Ron N, Groff, Michael W, Stadelmann, Marc A et al (2022) Improved estimates of strength and stiffness in pathologic vertebrae with bone metastases using CT-derived bone density compared with radiographic bone lesion quality classification. Journal of neurosurgery. Spine 36(1): 113–124 [PMC free article: PMC9210826] [PubMed: 34479191]	Population - does not match review protocol
Altehoefer, C, Ghanem, N, Hogerle, S et al (2001) Comparative detectability of bone metastases and impact on therapy of magnetic resonance imaging and bone scintigraphy in patients with breast cancer. European journal of radiology 40(1): 16–23 [PubMed: 11673003]	Population - does not match review protocol
Ambrosini, Valentina, Nanni, Cristina, Zompatori, Maurizio et al (2010) (68)Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours. European journal of nuclear medicine and molecular imaging 37(4): 722–7 [PubMed: 20107793]	Population - does not match review protocol
An, H S, Vaccaro, A R, Dolinskas, C A et al (1991) Differentiation between spinal tumors and infections with magnetic resonance imaging. Spine 16(8suppl): 334–8 [PubMed: 1785083]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Anatol’Evich Byvaltsev, V.; Stepanov, I.A.; Kichigin, A.I. (2019) The role of diffusion-weighted MRI of patients with spine metastases. Coluna/Columna 18(4): 289–293	Outcomes – do not match review protocol
Andreasson, I, Petren-Mallmin, M, Strang, P et al (1990) Diagnostic methods in planning palliation of spinal metastases. Anticancer research 10(3): 731–3 [PubMed: 1695079]	Outcomes - do not match review protocol
Anonymous. (2022) Correction to Lancet Oncol 2022; 23: 501–13 (The Lancet Oncology (2022) 23(4) (501–513), (S1470204522000924), (10.1016/S1470-2045(22)00092-4)). The Lancet Oncology 23(4): e161 [CrossRef]	Study design - does not match review protocol
Arevalo-Perez, Julio, Peck, Kyung K, Lyo, John K et al (2015) Differentiating benign from malignant vertebral fractures using T1 -weighted dynamic contrast-enhanced MRI. Journal of magnetic resonance imaging : JMRI 42(4): 1039–47 [PMC free article: PMC5525155] [PubMed: 25656545]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Asa, Sertac, Sonmezoglu, Kerim, Uslu-Besli, Lebriz et al (2021) Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT. Annals of nuclear medicine 35(8): 900–915 [PubMed: 33993425]	Population - does not match review protocol
Asilturk, Murad; Abdallah, Anas; Sofuoglu, Erhan Ozden (2020) Radiologic-Histopathologic Correlation of Adult Spinal Tumors: A Retrospective Study. Asian journal of neurosurgery 15(2): 354–362 [PMC free article: PMC7335153] [PubMed: 32656132]	Population - does not match review protocol
Baker, L L, Goodman, S B, Perkash, I et al (1990) Benign versus pathologic compression fractures of vertebral bodies: assessment with conventional spin-echo, chemical-shift, and STIR MR imaging. Radiology 174(2): 495–502 [PubMed: 2296658]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Baleriaux, D; Matos, C; De Greef, D (1993) Gadodiamide injection as a contrast medium for MRI of the central nervous system: a comparison with gadolinium-DOTA. Neuroradiology 35(7): 490–4 [PubMed: 8232870]	Comparator - does not match review protocol
Balliu, E, Vilanova, J C, Pelaez, I et al (2009) Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions. European journal of radiology 69(3): 560–6 [PubMed: 18276098]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Balogova, Sona, Zakoun, Joseph Ben, Michaud, Laure et al (2014) Whole-body 18F-fluorocholine (FCH) PET/CT and MRI of the spine for monitoring patients with castration-resistant prostate cancer metastatic to bone: a pilot study. Clinical nuclear medicine 39(11): 951–9 [PubMed: 25140552]	Outcomes - do not match review protocol
Baur, A, Huber, A, Ertl-Wagner, B et al (2001) Diagnostic value of increased diffusion weighting of a steady-state free precession sequence for differentiating acute benign osteoporotic fractures from pathologic vertebral compression fractures. AJNR. American journal of neuroradiology 22(2): 366–72 [PMC free article: PMC7973927] [PubMed: 11156785]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Baur, A, Stabler, A, Bruning, R et al (1998) Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology 207(2): 349–56 [PubMed: 9577479]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Baur, Andrea, Stabler, Axel, Arbogast, Susanne et al (2002) Acute osteoporotic and neoplastic vertebral compression fractures: fluid sign at MR imaging. Radiology 225(3): 730–5 [PubMed: 12461253]	Other protocol criteria - study reported in an included systematic review
Bazzocchi, Alberto, Spinnato, Paolo, Garzillo, Giorgio et al (2012) Detection of incidental vertebral fractures in breast imaging: the potential role of MR localisers. European radiology 22(12): 2617–23 [PubMed: 22688128]	Population – does not match protocol
Beeler, Whitney H, Paradis, Kelly C, Gemmete, Joseph J et al (2019) Computed Tomography Myelosimulation Versus Magnetic Resonance Imaging Registration to Delineate the Spinal Cord During Spine Stereotactic Radiosurgery. World neurosurgery 122: e655–e666 [PubMed: 30992117]	Index test – does not match protocol
Bhugaloo, Aa, Abdullah, Bjj, Siow, Ys et al (2006) Diffusion weighted MR imaging in acute vertebral compression fractures: differentiation between malignant and benign causes. Biomedical imaging and intervention journal 2(2): e12 [PMC free article: PMC3097619] [PubMed: 21614224]	Other protocol criteria - study reported in an included systematic review (Liu 2019)
Bierry, Guillaume, Venkatasamy, Aina, Kremer, Stephane et al (2014) Dual-energy CT in vertebral compression fractures: performance of visual and quantitative analysis for bone marrow edema demonstration with comparison to MRI. Skeletal radiology 43(4): 485–92 [PubMed: 24445957]	Population – does not match protocol
Boesen, J, Johnsen, A, Helweg-Larsen, S et al (1991) Diagnostic value of spinal computer tomography in patients with intraspinal metastases causing complete block on myelography. Acta radiologica (Stockholm, Sweden : 1987) 32(1): 1–2 [PubMed: 2012721]	Outcomes – do not match protocol
Bohdiewicz, Paul J, Wong, Ching-Yee O, Kondas, David et al (2003) High predictive value of F-18 FDG PET patterns of the spine for metastases or benign lesions with good agreement between readers. Clinical nuclear medicine 28(12): 966–70 [PubMed: 14663317]	Outcomes – do not match protocol
Bohuslavizki, K.H., Klutmann, S., Buchert, R. et al (1999) Value of F-18-FOG PET in patients with cervical lymph node metastases of unknown origin. Radiology and Oncology 33(3): 207–213	Population – does not match protocol
Boker, Sarah M, Adams, Lisa C, Bender, Yvonne Y et al (2019) Differentiation of Predominantly Osteoblastic and Osteolytic Spine Metastases by Using Susceptibility-weighted MRI. Radiology 290(1): 146–154 [PubMed: 30375926]	Comparator – does not match protocol
Boogerd, W. and Kroger, R. (1991) Intravenous contrast in spinal computed tomography to identify epidural metastases. Clinical Neurology and Neurosurgery 93(3): 195–199 [PubMed: 1660371]	Outcomes – do not match protocol
Boogerd, W; van der Sande, J J; Kroger, R (1992) Early diagnosis and treatment of spinal epidural metastasis in breast cancer: a prospective study. Journal of neurology, neurosurgery, and psychiatry 55(12): 1188–93 [PMC free article: PMC1015337] [PubMed: 1479399]	Outcomes – do not match protocol
Borggrefe, Jan, Neuhaus, Victor-Frederic, Le Blanc, Markus et al (2019) Accuracy of iodine density thresholds for the separation of vertebral bone metastases from healthy-appearing trabecular bone in spectral detector computed tomography. European radiology 29(6): 3253–3261 [PubMed: 30523450]	Index test – does not match protocol
Bredella, Miriam A, Essary, Brendan, Torriani, Martin et al (2008) Use of FDG-PET in differentiating benign from malignant compression fractures. Skeletal radiology 37(5): 405–13 [PMC free article: PMC2271083] [PubMed: 18278491]	Other protocol criteria - study reported in an included systematic review (Kim 2020)
Brunner, P., Chanalet, S., Sedat, J. et al (2002) Percutaneous infiltrations of cervical, thoracic, and lumbar spine. Seminars in Interventional Radiology 19(3): 219–228	Intervention – does not match protocol
Buhmann Kirchhoff, Sonja, Becker, Christoph, Duerr, Hans Roland et al (2009) Detection of osseous metastases of the spine: comparison of high resolution multi-detector-CT with MRI. European journal of radiology 69(3): 567–73 [PubMed: 18191356]	Population – does not match protocol - unclear how patients were identified for the study
Burns, Joseph E, Yao, Jianhua, Wiese, Tatjana S et al (2013) Automated detection of sclerotic metastases in the thoracolumbar spine at CT. Radiology 268(1): 69–78 [PMC free article: PMC3689444] [PubMed: 23449957]	Population – does not match protocol - case control design
Buyukdereli, Gulgun, Ermin, Tahsin, Kara, Oguz et al (2006) Tc-99m MIBI uptake in traumatic vertebral fractures and metastatic vertebral lesions: comparison with Tc-99m MDP. Advances in therapy 23(1): 33–8 [PubMed: 16644620]	Outcomes – do not match protocol
Byun, Woo Mok, Jang, Han Won, Kim, Sang Woo et al (2007) Diffusion-weighted magnetic resonance imaging of sacral insufficiency fractures: comparison with metastases of the sacrum. Spine 32(26): e820–4 [PubMed: 18091477]	Outcomes – do not match protocol
Byun, Woo Mok, Shin, Sei One, Chang, Yongmin et al (2002) Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of response to therapy. AJNR. American journal of neuroradiology 23(6): 906–12 [PMC free article: PMC7976927] [PubMed: 12063214]	Population – does not match protocol
Castillo, M, Arbelaez, A, Smith, J K et al (2000) Diffusion-weighted MR imaging offers no advantage over routine noncontrast MR imaging in the detection of vertebral metastases. AJNR. American journal of neuroradiology 21(5): 948–53 [PMC free article: PMC7976774] [PubMed: 10815675]	Population – does not match protocol
Castroneves, LA, Coura Filho, G, de Freitas, RMC et al (2018) Comparison of 68Ga PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases. The Journal of clinical endocrinology and metabolism 103(9): 3250–3259 [PubMed: 29846642]	Population – does not match protocol
Chabot, M.C. and Herkowitz, H.N. (1995) Spine tumors: Patient evaluation. Seminars in Spine Surgery 7(4): 260–268	Study design – does not match protocol
Chadwick, D.J., Gingell, J.C., Gillatt, D.A. et al (1991) Magnetic resonance imaging of spinal metastases. Journal of the Royal Society of Medicine 84(4): 196–200 [PMC free article: PMC1293180] [PubMed: 2027142]	Outcomes – does not match protocol
Chan, J H M, Peh, W C G, Tsui, E Y K et al (2002) Acute vertebral body compression fractures: discrimination between benign and malignant causes using apparent diffusion coefficients. The British journal of radiology 75(891): 207–14 [PubMed: 11932212]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Chan, Jimmy Yu Wai, Chan, Richie Chiu Lung, Chow, Velda Ling Yu et al (2013) Efficacy of fine-needle aspiration in diagnosing cervical nodal metastasis from nasopharyngeal carcinoma after radiotherapy. The Laryngoscope 123(1): 134–9 [PubMed: 22907783]	Population – does not match protocol
Chen, C J and Hsu, W C (1997) Imaging findings of spontaneous spinal epidural hematoma. Journal of the Formosan Medical Association = Taiwan yi zhi 96(4): 283–7 [PubMed: 9136517]	Population – does not match protocol
Chen, Hongliang, Xie, Biao, Zhong, Xin et al (2021) Magnetic Resonance Image under Variable Model Algorithm in Diagnosis of Patients with Spinal Metastatic Tumors. Contrast media & molecular imaging 2021:1381274 [PMC free article: PMC8384545] [PubMed: 34483780]	Comparator – does not match protocol
Chen, Y, Zhang, E, Wang, Q et al (2021) Use of dynamic contrast-enhanced MRI for the early assessment of outcome of CyberKnife stereotactic radiosurgery for patients with spinal metastases. Clinical radiology 76(11): 864e1–864e6 [PubMed: 34404514]	Outcomes – do not match protocol
Chiewvit, Pipat, Danchaivijitr, Nasuda, Sirivitmaitrie, Kaewta et al (2009) Does magnetic resonance imaging give value-added than bone scintigraphy in the detection of vertebral metastasis?. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 92(6): 818–29 [PubMed: 19530588]	Population – does not match protocol
Cho, Se Jin, Suh, Chong Hyun, Baek, Jung Hwan et al (2019) Diagnostic performance of CT in detection of metastatic cervical lymph nodes in patients with thyroid cancer: a systematic review and meta-analysis. European radiology 29(9): 4635–4647 [PubMed: 30806803]	Population – does not match protocol
Cho, Won-Ik and Chang, Ung-Kyu (2011) Comparison of MR imaging and FDG-PET/CT in the differential diagnosis of benign and malignant vertebral compression fractures. Journal of neurosurgery. Spine 14(2): 177–83 [PubMed: 21214309]	Other protocol criteria - study reported in an included systematic review (Kim 2020)
Ciray, I, Lindman, H, Astrom, K G et al (2001) Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging. Acta radiologica (Stockholm, Sweden : 1987) 42(2): 198–206 [PubMed: 11259949]	Population – does not match protocol
Colletti, P M, Dang, H T, Deseran, M W et al (1991) Spinal MR imaging in suspected metastases: correlation with skeletal scintigraphy. Magnetic resonance imaging 9(3): 349–55 [PubMed: 1881253]	Outcomes – do not match protocol
Colletti, P M, Siegel, H J, Woo, M Y et al (1996) The impact on treatment planning of MRI of the spine in patients suspected of vertebral metastasis: an efficacy study. Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society 20(3): 159–62 [PubMed: 8930468]	Outcomes – do not match protocol
Cook, A M, Lau, T N, Tomlinson, M J et al (1998) Magnetic resonance imaging of the whole spine in suspected malignant spinal cord compression: impact on management. Clinical oncology (Royal College of Radiologists (Great Britain)) 10(1): 39–43 [PubMed: 9543614]	Outcomes – do not match protocol
Cox, M., Pukenas, B., Poplawski, M. et al (2016) CT-guided Cervical Bone Biopsy in 43 Patients: Diagnostic Yield and Safety at Two Large Tertiary Care Hospitals. Academic Radiology 23(11): 1372–1375 [PubMed: 27555546]	Outcomes – do not match protocol
Cuenod, C A, Laredo, J D, Chevret, S et al (1996) Acute vertebral collapse due to osteoporosis or malignancy: appearance on unenhanced and gadolinium-enhanced MR images. Radiology 199(2): 541–9 [PubMed: 8668809]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Dandekar, M R, Kannan, S, Rangarajan, V et al (2011) Utility of PET in unknown primary with cervical metastasis: a retrospective study. Indian journal of cancer 48(2): 181–6 [PubMed: 21768663]	Population – does not match protocol
De Bruin, H.G., Algra, P.R., Kruyt, R.H. et al (1999) Comparison of the FISP 2D sequence with spin echo T1 weighted images before and after intravenous Gd-chelates in detection and evaluation of spinal metastases. Image Decisions MRI 3(4): 10–15	Other protocol criteria – not available in English
Delpassand, E S, Garcia, J R, Bhadkamkar, V et al (1995) Value of SPECT imaging of the thoracolumbar spine in cancer patients. Clinical nuclear medicine 20(12): 1047–51 [PubMed: 8674287]	Outcomes – do not match protocol
Demirdogen, Ezgi, Ursavas, Ahmet, Aydin Guclu, Ozge et al (2020) Diagnostic performance of EBUS-TBNA and its interrelation with PET-CT in patients with extra-thoracic malignancies. Tuberkuloz ve toraks 68(3): 285–292 [PubMed: 33295727]	Intervention – does not match protocol
Donners, R., Hirschmann, A., Gutzeit, A. et al (2021) T2-weighted Dixon MRI of the spine: A feasibility study of quantitative vertebral bone marrow analysis. Diagnostic and Interventional Imaging 102(78): 431–438 [PubMed: 33612414]	Population – does not match protocol
Douis, H, Davies, A M, Jeys, L et al (2016) Chemical shift MRI can aid in the diagnosis of indeterminate skeletal lesions of the spine. European radiology 26(4): 932–40 [PubMed: 26162578]	Other protocol criteria - study reported in an included systematic review (Suh 2018)
Eissawy, M.G., Saadawy, A.M.I., Farag, K. et al (2021) Accuracy and diagnostic value of diffusion-weighted whole body imaging with background body signal suppression (DWIBS) in metastatic breast cancer. Egyptian Journal of Radiology and Nuclear Medicine 52(1): 74	Population – does not match protocol
Facon, David, Ozanne, Augustin, Fillard, Pierre et al (2005) MR diffusion tensor imaging and fiber tracking in spinal cord compression. AJNR. American journal of neuroradiology 26(6): 1587–94 [PMC free article: PMC8149058] [PubMed: 15956535]	Outcomes – do not match protocol
Faiella, E., Santucci, D., Calabrese, A. et al (2022) Artificial Intelligence in Bone Metastases: An MRI and CT Imaging Review. International Journal of Environmental Research and Public Health 19(3): 1880 [PMC free article: PMC8834956] [PubMed: 35162902]	Population – does not match protocol
Fan, Xiaojie, Zhang, Xiaoyu, Zhang, Zibo et al (2021) Deep Learning on MRI Images for Diagnosis of Lung Cancer Spinal Bone Metastasis. Contrast media & molecular imaging 2021: 5294379 [PMC free article: PMC8294999] [PubMed: 34354553]	Other protocol criteria - study reported in an included systematic review (Faiella 2022)
Fan, Xin, Zhang, Han, Yin, Yuzhen et al (2020) Texture Analysis of 18F-FDG PET/CT for Differential Diagnosis Spinal Metastases. Frontiers in medicine 7: 605746 [PMC free article: PMC7843930] [PubMed: 33521018]	Intervention – does not match protocol
Feroz, Imza, Makhdoomi, Rumana Hamid, Khursheed, Nayil et al (2018) Utility of Computed Tomography-guided Biopsy in Evaluation of Metastatic Spinal Lesions. Asian journal of neurosurgery 13(3): 577–584 [PMC free article: PMC6159094] [PubMed: 30283508]	Outcomes – do not match protocol
Filograna, Laura, Lenkowicz, Jacopo, Cellini, Francesco et al (2019) Identification of the most significant magnetic resonance imaging (MRI) radiomic features in oncological patients with vertebral bone marrow metastatic disease: a feasibility study. La Radiologia medica 124(1): 50–57 [PubMed: 30191445]	Other protocol criteria - study reported in an included systematic review (Faiella 2022)
Frank, J A, Ling, A, Patronas, N J et al (1990) Detection of malignant bone tumors: MR imaging vs scintigraphy. AJR. American journal of roentgenology 155(5): 1043–8 [PubMed: 2120933]	Population – does not match protocol
Freire, A.R.S., Lima, E.N.P., Almeida, O.P. et al (2003) Computed tomography and lymphoscintigraphy to identify lymph node metastases and lymphatic drainage pathways in oral and oropharyngeal squamous cell carcinomas. European Archives of Oto-Rhino-Laryngology 260(3): 148–152 [PubMed: 12687387]	Population – does not match protocol
Fu, Tsai-Sheng, Chen, Li-Hui, Liao, Jen-Chung et al (2004) Magnetic resonance imaging characteristics of benign and malignant vertebral fractures. Chang Gung medical journal 27(11): 808–15 [PubMed: 15796256]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Gabriel, Michael, Decristoforo, Clemens, Donnemiller, Eveline et al (2003) An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. Journal of nuclear medicine 44(5): 708–16 [PubMed: 12732671]	Population – does not match protocol
Gao, Y, Fang, J, Liu, X et al (2006) [Diagnostic value of nuclide bone imaging for bone metastasis from lung cancer and clinic analysis]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 9(4): 357–61 [PubMed: 21176456]	Population – does not match protocol
Gauthe, Mathieu, Testart Dardel, Nathalie, Ruiz Santiago, Fernando et al (2018) Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?. European radiology 28(9): 3943–3952 [PubMed: 29532242]	Population – does not match protocol
Geith, Tobias, Biffar, Andreas, Schmidt, Gerwin et al (2015) Physiological Background of Differences in Quantitative Diffusion-Weighted Magnetic Resonance Imaging Between Acute Malignant and Benign Vertebral Body Fractures: Correlation of Apparent Diffusion Coefficient With Quantitative Perfusion Magnetic Resonance Imaging Using the 2-Compartment Exchange Model. Journal of computer assisted tomography 39(5): 643–8 [PubMed: 26248148]	Outcomes – do not match protocol
Geith, Tobias, Biffar, Andreas, Schmidt, Gerwin et al (2013) Quantitative analysis of acute benign and malignant vertebral body fractures using dynamic contrast-enhanced MRI. AJR. American journal of roentgenology 200(6): w635–43 [PubMed: 23701095]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Geith, Tobias, Schmidt, Gerwin, Biffar, Andreas et al (2014) Quantitative evaluation of benign and malignant vertebral fractures with diffusion-weighted MRI: what is the optimum combination of b values for ADC-based lesion differentiation with the single-shot turbo spin-echo sequence?. American journal of roentgenology 203(3): 582–8 [PubMed: 25148160]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Geneidi, E.A.S.; Ali, H.I.; Dola, E.F. (2016) Role of DWI in characterization of bone tumors. Egyptian Journal of Radiology and Nuclear Medicine 47(3): 919–927	Population – does not match protocol
Ghanem, Nadir Alexander, Pache, Gregor, Lohrmann, Christian et al (2007) MRI and (18)FDG-PET in the assessment of bone marrow infiltration of the spine in cancer patients. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 16(11): 1907–12 [PMC free article: PMC2223344] [PubMed: 17404763]	Outcomes – do not match protocol
Gosfield, E 3rd; Alavi, A; Kneeland, B (1993) Comparison of radionuclide bone scans and magnetic resonance imaging in detecting spinal metastases. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 34(12): 2191–8 [PubMed: 8254410]	Population – does not match protocol
Gravel, Guillaume, Tselikas, Lambros, Moulin, Benjamin et al (2019) Early detection with MRI of incomplete treatment of spine metastases after percutaneous cryoablation. European radiology 29(10): 5655–5663 [PubMed: 30877460]	Outcomes – do not match protocol
Gross, N.D., Weissman, J.L., Talbot, J.M. et al (2001) MRI detection of cervical metastasis from differentiated thyroid carcinoma. Laryngoscope 111(11i): 1905–1909 [PubMed: 11801967]	Population – does not match protocol
Gualdi, GF, Casciani, E, Di Biasi, C et al (1999) [The role of TC and MRI in the identification, characterization and staging of tumors of the spinal vertebrae]. La Clinica terapeutica 150(1): 51–65 [PubMed: 10367545]	Other protocol criteria – not available in English
Guan, Youxin, Peck, Kyung K, Lyo, John et al (2020) T1-weighted Dynamic Contrast-enhanced MRI to Differentiate Nonneoplastic and Malignant Vertebral Body Lesions in the Spine. Radiology 297(2): 382–389 [PMC free article: PMC7643814] [PubMed: 32870135]	Population – does not match protocol
Guo, Marissa, Kolberg, Kristen L, Smith, Eleanor C et al (2018) Predominance of Spinal Metastases Involving the Posterior Vertebral Body. World neurosurgery 119: e991–e996 [PubMed: 30114534]	Outcomes – do not match protocol
Guo, Shuai, Chen, Jie, Yang, Baohui et al (2016) Establishment and evaluation of a prognostic model for surgical outcomes of patients with atlanto-axial dislocations. The Journal of international medical research 44(6): 1474–1482 [PMC free article: PMC5536767] [PubMed: 28322106]	Population – does not match protocol
Gupta, A., Chaturvedi, S., Jha, D. et al (2019) Revisiting metastatic central nervous system tumors with unknown primary using clinicopathological findings: A single neurosciences institutional study. Indian Journal of Pathology and Microbiology 62(3): 368–374 [PubMed: 31361222]	Intervention – does not match protocol
Ha, Ji Y, Jeon, Kyung N, Bae, Kyungsoo et al (2017) Effect of Bone Reading CT software on radiologist performance in detecting bone metastases from breast cancer. The British journal of radiology 90(1072): 20160809 [PMC free article: PMC5605069] [PubMed: 28256905]	Population – does not match protocol
Hahn, Seok; Lee, Young Han; Suh, Jin-Suck (2018) Detection of vertebral metastases: a comparison between the modified Dixon turbo spin echo T2 weighted MRI and conventional T1 weighted MRI: a preliminary study in a tertiary centre. The British journal of radiology 91 (1085): 20170782 [PMC free article: PMC6190773] [PubMed: 29393668]	Population – does not match protocol
Hammon, Matthias, Dankerl, Peter, Tsymbal, Alexey et al (2013) Automatic detection of lytic and blastic thoracolumbar spine metastases on computed tomography. European radiology 23(7): 1862–70 [PMC free article: PMC3674341] [PubMed: 23397381]	Intervention – does not match protocol
Han, L J, Au-Yong, T K, Tong, W C et al (1998) Comparison of bone single-photon emission tomography and planar imaging in the detection of vertebral metastases in patients with back pain. European journal of nuclear medicine 25(6): 635–8 [PubMed: 9618579]	Population – does not match protocol
Hao, S P and Ng, S H (2000) Magnetic resonance imaging versus clinical palpation in evaluating cervical metastasis from head and neck cancer. Otolaryngology--head and neck surgery, 123(3): 324–7 [PubMed: 10964315]	Population – does not match protocol
Harrison, S K; Ditchfield, M R; Waters, K (1998) Correlation of MRI and CSF cytology in the diagnosis of medulloblastoma spinal metastases. Pediatric radiology 28(8): 571–4 [PubMed: 9716623]	Population – does not match protocol - medulloblastoma
Henschke, Nicholas, Maher, Christopher G, Ostelo, Raymond W J G et al (2013) Red flags to screen for malignancy in patients with low-back pain. The Cochrane database of systematic reviews: cd008686 [PMC free article: PMC10631455] [PubMed: 23450586]	Intervention – does not match protocol - no imaging tests evaluated
Hoogcarspel, Stan J, Van der Velden, Joanne M, Lagendijk, Jan J W et al (2014) The feasibility of utilizing pseudo CT-data for online MRI based treatment plan adaptation for a stereotactic radiotherapy treatment of spinal bone metastases. Physics in medicine and biology 59(23): 7383–91 [PubMed: 25386792]	Outcomes – do not match protocol
Horakova, M., Horak, T., Valosek, J. et al (2022) Semi-automated detection of cervical spinal cord compression with the Spinal Cord Toolbox. Quantitative Imaging in Medicine and Surgery 12(4): 2261–2279 [PMC free article: PMC8923862] [PubMed: 35371944]	Population – does not match protocol
Hoshiai, Sodai, Masumoto, Tomohiko, Hanaoka, Shouhei et al (2019) Clinical usefulness of temporal subtraction CT in detecting vertebral bone metastases. European journal of radiology 118: 175–180 [PubMed: 31439238]	Population – does not match protocol
Hsu, H.-C., Liao, T.-Y., Ro, L.-S. et al (2019) Differences in Pain Intensity of Tumors Spread to the Anterior versus Anterolateral/Lateral Portions of the Vertebral Body Based on CT Scans. Pain Research and Management 2019: 9387941 [PMC free article: PMC6535837] [PubMed: 31214273]	Outcomes – do not match protocol
Huang, C W C, Ali, A, Chang, Y-M et al (2020) Major Radiologic and Clinical Outcomes of Total Spine MRI Performed in the Emergency Department at a Major Academic Medical Center. AJNR. American journal of neuroradiology 41(6): 1120–1125 [PMC free article: PMC7342750] [PubMed: 32439645]	Population – does not match protocol
Huang, T.-W., Chao, P.-C., Ou, J.-J. et al (2006) Cervical spine metastases secondary to colorectal carcinoma: The role of MR imaging and treatment strategy. Journal of Medical Sciences 26(6): 215–218	Outcomes – do not match protocol
Iagaru, A., Young, P., Mittra, E. et al (2013) Pilot prospective evaluation of 99mTc-MDP scintigraphy, 18F NaF PET/CT, 18F FDG PET/CT and whole-body MRI for detection of skeletal metastases. Clinical Nuclear Medicine 38(7): e290–e296 [PubMed: 23455520]	Population – does not match protocol
Ichimaru, K., Endo, K., Ito, K. et al (1995) Spinal cord tumours: Diagnosis with myelogram of MRI?. Journal of Orthopaedic Surgery 3(2): 35–39	Population – does not match protocol
Jacobson, A F, Cronin, E B, Stomper, P C et al (1990) Bone scans with one or two new abnormalities in cancer patients with no known metastases: frequency and serial scintigraphic behavior of benign and malignant lesions. Radiology 175(1): 229–32 [PubMed: 2315486]	Population – does not match protocol
Kakitsubata, Yousuke, Theodorou, Daphne J, Theodorou, Stavroula J et al (2009) Metastatic disease involving the discovertebral junction of the spine. Joint bone spine 76(1): 50–6 [PubMed: 18977681]	Population – does not match protocol - cadaveric study
Karchevsky, Michael; Babb, James S; Schweitzer, Mark E (2008) Can diffusion-weighted imaging be used to differentiate benign from pathologic fractures? A meta-analysis. Skeletal radiology 37(9): 791–5 [PubMed: 18551290]	Outcomes – do not match protocol – does not report data relevant to diagnostic accuracy
Kaufman, B A; Moran, C J; Park, T S (1995) Spinal magnetic resonance imaging immediately after craniotomy for detection of metastatic disease. Pediatric neurosurgery 23(4): 171–81 [PubMed: 8835206]	Population – does not match protocol
Kelly, Hillary R and Curtin, Hugh D (2017) Chapter 2 Squamous Cell Carcinoma of the Head and Neck-Imaging Evaluation of Regional Lymph Nodes and Implications for Management. Seminars in ultrasound, CT, and MR 38(5): 466–478 [PubMed: 29031364]	Population – does not match protocol
Kerslake, R W; Jaspan, T; Worthington, B S (1991) Magnetic resonance imaging of spinal trauma. The British journal of radiology 64(761): 386–402 [PubMed: 2036560]	Population – does not match protocol
Khan, A., Gao, A., Hall, E. et al (2017) Do Routine Computed Tomography Scans Detect Early Spinal Cord Compression in Patients with Castrate Resistant Prostate Cancer? Implications for the PROMPTS Trial. Clinical Oncology 29(3): e87–e87	Publication type – does not match protocol
Kim, D.W., Kim, S.C., Krynyckyi, B.R. et al (2005) Focally increased activity in the lateral aspect of the mid cervical spine on bone scintigraphy is almost always benign in nature. Clinical Nuclear Medicine 30(9): 593–595 [PubMed: 16100474]	Outcomes – do not match protocol
Kim, Seong-Jang and Lee, Jung Sub (2020) Diagnostic Performance of F-18 Fluorodeoxyglucose Positron Emission Tomography or Positron Emission Tomography/Computed Tomography for Differentiation of Benign and Malignant Vertebral Compression Fractures: A Meta-Analysis. World neurosurgery 137: e626–e633 [PubMed: 32105873]	Other protocol criteria – duplicate publication
Kizilay, F., Sahin, M., Simsir, A. et al (2020) Predictive value of bone scintigraphy in the diagnosis of prostate cancer bone metastases and comparison of verification methods. Kuwait Medical Journal 52(4): 368–374	Population – does not match protocol
Kosuda, S, Kaji, T, Yokoyama, H et al (1996) Does bone SPECT actually have lower sensitivity for detecting vertebral metastasis than MRI?. Journal of nuclear medicine, 37(6): 975–8 [PubMed: 8683325]	Outcomes – do not match protocol
Krabbe, Christiaan A, van der Werff-Regelink, Gerreke, Pruim, Jan et al (2010) Detection of cervical metastases with (11)C-tyrosine PET in patients with squamous cell carcinoma of the oral cavity or oropharynx: A comparison with (18)F-FDG PET. Head & neck 32(3): 368–74 [PubMed: 19626632]	Population – does not match protocol
Kubota, Takao, Yamada, Kei, Ito, Hirotoshi et al (2005) High-resolution imaging of the spine using multidetector-row computed tomography: differentiation between benign and malignant vertebral compression fractures. Journal of computer assisted tomography 29(5): 712–9 [PubMed: 16163049]	Outcomes – do not match protocol
Lang, Ning, Su, Min-Ying, Yu, Hon J et al (2013) Differentiation of myeloma and metastatic cancer in the spine using dynamic contrast-enhanced MRI. Magnetic resonance imaging 31(8): 1285–91 [PMC free article: PMC3620894] [PubMed: 23290477]	Reference standard – does not match protocol
Lauenstein, T.C., Freudenberg, L.S., Goehde, S.C. et al (2002) Whole-body MRI using a rolling table platform for the detection of bone metastases. European Radiology 12(8): 2091–2099 [PubMed: 12136329]	Index test – does not match protocol
Lee, Eugene, Lee, Joon Woo, Lee, Jinyoung et al (2016) Acute benign vertebral compression fractures: “see-through sign” on contrast-enhanced MR images. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 25(11): 3470–3477 [PubMed: 26538157]	Outcomes – do not match protocol
Li, X F, Yang, Y, Lin, C B et al (2016) Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 49(1): e4769 [PMC free article: PMC4681415] [PubMed: 26628393]	Outcomes – do not match protocol
Libshitz, H I, Malthouse, S R, Cunningham, D et al (1992) Multiple myeloma: appearance at MR imaging. Radiology 182(3): 833–7 [PubMed: 1535904]	Population – does not match protocol
Lin, Fan; Lei, Yi; Li, Yang-bin (2009) Influence of lesion ratio on diagnostic performance of in-phase/opposed-phase imaging and apparent diffusion coefficient for differentiating acute benign vertebral fractures and metastases. Chinese medical journal 122(11): 1293–9 [PubMed: 19567140]	Other protocol criteria - study reported in an included systematic review (Suh 2018)
Liu, H., Jiao, M., Yuan, Y. et al (2022) Benign and malignant diagnosis of spinal tumors based on deep learning and weighted fusion framework on MRI. Insights into Imaging 13(1): 87 [PMC free article: PMC9091071] [PubMed: 35536493]	Comparator – does not match protocol
Liu, J., Guo, W., Zeng, P. et al (2022) Vertebral MRI-based radiomics model to differentiate multiple myeloma from metastases: influence of features number on logistic regression model performance. European Radiology 32(1): 572–581 [PubMed: 34255157]	Comparator – does not match protocol
Liu, Peng, Liang, Yun, Bian, Chong et al (2020) Diagnostic accuracy of MR, CT, and ECT in the differentiation of neoplastic from nonneoplastic spine lesions. Asia-Pacific journal of clinical oncology 16(5): e192-e197 [PubMed: 32506805]	Population – does not match protocol
Liu, Tao, Wang, Shenghao, Liu, Hao et al (2017) Detection of vertebral metastases: a meta-analysis comparing MRI, CT, PET, BS and BS with SPECT. Journal of cancer research and clinical oncology 143(3): 457–465 [PubMed: 27752772]	Systematic review - included studies were assessed for relevance
Luboldt, W, Küfer, R, Blumstein, N et al (2008) Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases. Radiology 249(3): 1017–25 [PubMed: 18849502]	Outcomes – do not match protocol
Luo, Zhanpeng, Litao, Li, Gu, Suxi et al (2016) Standard-b-value vs low-b-value DWI for differentiation of benign and malignant vertebral fractures: a meta-analysis. The British journal of radiology 89(1058): 20150384 [PMC free article: PMC4985191] [PubMed: 26612466]	Outcomes – does not match protocol
Lv, Mu, Zhou, Zhichao, Tang, Qingkun et al (2020) Differentiation of usual vertebral compression fractures using CT histogram analysis as quantitative biomarkers: A proof-of-principle study. European journal of radiology 131: 109264 [PubMed: 32920220]	Intervention – does not match protocol
Maeda, Masayuki, Sakuma, Hajime, Maier, Stephan E et al (2003) Quantitative assessment of diffusion abnormalities in benign and malignant vertebral compression fractures by line scan diffusion-weighted imaging. AJR. American journal of roentgenology 181(5): 1203–9 [PubMed: 14573404]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Mahnken, Andreas H, Wildberger, Joachim E, Adam, Gerhard et al (2005) Is there a need for contrast-enhanced T1-weighted MRI of the spine after inconspicuous short tau inversion recovery imaging?. European radiology 15(7): 1387–92 [PubMed: 15776239]	Outcomes – do not match protocol
Maralani, P.J., Lo, S.S., Redmond, K. et al (2017) Spinal metastases: multimodality imaging in diagnosis and stereotactic body radiation therapy planning. Future Oncology 13(1): 77–91 [PubMed: 27523190]	Study design – does not match protocol
Matsumoto, Yoshihiro, Harimaya, Katsumi, Kawaguchi, Kenichi et al (2016) Dumbbell Scoring System: A New Method for the Differential Diagnosis of Malignant and Benign Spinal Dumbbell Tumors. Spine 41(20): e1230–e1236 [PubMed: 27031767]	Population – does not match protocol
McKinley, W O, Conti-Wyneken, A R, Vokac, C W et al (1996) Rehabilitative functional outcome of patients with neoplastic spinal cord compressions. Archives of physical medicine and rehabilitation 77(9): 892–5 [PubMed: 8822680]	Intervention – does not match protocol
Meena, Rajesh, Aggarwal, Ashish, Bhattacharya, Anish et al (2019) Non traumatic vertebral lesions: incremental utility of PET-CT over MRI and FNAC in a suggested diagnostic algorithm. British journal of neurosurgery 33(1): 25–29 [PubMed: 28282998]	Population – does not match protocol
Mehta, R C, Marks, M P, Hinks, R S et al (1995) MR evaluation of vertebral metastases: T1-weighted, short-inversion-time inversion recovery, fast spin-echo, and inversion-recovery fast spin-echo sequences. AJNR. American journal of neuroradiology 16(2): 281–8 [PMC free article: PMC8338328] [PubMed: 7726074]	Outcomes – do not match protocol
Metin, M., Ergin, M., Solak, O. et al (2012) Effectiveness of PET scan in postoperative long term follow up of patients with nonsmall cell lung cancer. Journal of Clinical and Analytical Medicine 3(1): 30–32	Population – does not match protocol
Metser, Ur, Lerman, Hedva, Blank, Annat et al (2004) Malignant involvement of the spine: assessment by 18F-FDG PET/CT. Journal of nuclear medicine, 45(2): 279–84 [PubMed: 14960648]	Population – does not match protocol
Mihoubi Bouvier, Fadila, Thomas De Montpreville, Vincent, Besse, Benjamin et al (2021) Can MRI differentiate surrounding vertebral invasion from reactive inflammatory changes in superior sulcus tumor?. European radiology 31(12): 8991–8999 [PubMed: 33991225]	Population – does not match protocol
Mohson, K.I.; Naief, Q.T.; Jalil, F.A. (2020) Differentiating benign from suspicious vertebral marrow lesions detected with conventional magnetic resonance imaging using apparent diffusion coefficient and diffusion-weighted image. Open Access Macedonian Journal of Medical Sciences 8(b): 114–118	Outcomes – do not match protocol
Mossa-Basha, M., Gerszten, P.C., Myrehaug, S. et al (2019) Spinal metastasis: Diagnosis, management and followup. British Journal of Radiology 92(1103): 20190211 [PMC free article: PMC6849675] [PubMed: 31322920]	Study design – does not match protocol
Mostardi, P M, Diehn, F E, Rykken, J B et al (2014) Intramedullary spinal cord metastases: visibility on PET and correlation with MRI features. AJNR. American journal of neuroradiology 35(1): 196–201 [PMC free article: PMC7966499] [PubMed: 23886743]	Outcomes – do not match protocol
Mubarak, Fatima and Akhtar, Waseem (2011) Acute vertebral compression fracture: differentiation of malignant and benign causes by diffusion weighted magnetic resonance imaging. JPMA. The Journal of the Pakistan Medical Association 61(6): 555–8 [PubMed: 22204209]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Nakanishi, K, Kobayashi, M, Nakaguchi, K et al (2007) Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion-weighted images. Magnetic resonance in medical sciences, 6(3): 147–55 [PubMed: 18037795]	Population – does not match protocol
Narin, Y., Urhan, M., Canpolat, N. et al (2007) Lesion detectability and clinical effectiveness of dual-head coincidence gamma camera imaging in comparison with dedicated PET systems in tumour patients. Journal of International Medical Research 35(4): 467–473 [PubMed: 17697523]	Population – does not match protocol
Nozaki, T, Yasuda, K, Akashi, T et al (2008) Usefulness of single photon emission computed tomography imaging in the detection of lumbar vertebral metastases from prostate cancer. International journal of urology : official journal of the Japanese Urological Association 15(6): 516–9 [PubMed: 18422581]	Population – does not match protocol
Ohlmann-Knafo, S, Tarnoki, A D, Tarnoki, D L et al (2015) MR Diagnosis of Bone Metastases at 1.5 T and 3 T: Can STIR Imaging Be Omitted?. RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 187(10): 924–32 [PubMed: 26085176]	Population – does not match protocol
Ohno, Seiichiro, Togami, Izumi, Sei, Tetsuro et al (2003) MR imaging of vertebral metastases at 0.2 Tesla: clinical evaluation of T1-weighted opposed-phase gradient-echo imaging. Physiological chemistry and physics and medical NMR 35(2): 145–56 [PubMed: 15552725]	Other protocol criteria - study reported in an included systematic review (Suh 2018)
Otake, S, Matsuo, M, Tamaki, T et al (1991) [Fast MR imaging of liver metastasis using FLASH and FISP--optimal sequences for T1- and T2*-weighted images]. Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica 51(1): 19–32 [PubMed: 2011477]	Population – does not match protocol
Oztekin, Ozgur, Ozan, Ebru, Hilal Adibelli, Zehra et al (2009) SSH-EPI diffusion-weighted MR imaging of the spine with low b values: is it useful in differentiating malignant metastatic tumor infiltration from benign fracture edema?. Skeletal radiology 38(7): 651–8 [PubMed: 19252906]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Park, Chankue, Lee, Joon Woo, Kim, Yongju et al (2019) Diagnosis of spinal metastasis: are MR images without contrast medium application sufficient?. Clinical imaging 55: 165–173 [PubMed: 30904626]	Publication type – does not match protocol
Park, Hee Jin, Lee, So Yeon, Rho, Myung Ho et al (2016) Single-Shot Echo-Planar Diffusion-Weighted MR Imaging at 3T and 1.5T for Differentiation of Benign Vertebral Fracture Edema and Tumor Infiltration. Korean journal of radiology 17(5): 590–7 [PMC free article: PMC5007386] [PubMed: 27587948]	Population – does not match protocol
Park, Sang-Min, Park, Jae-Woo, Lee, Hui-Jong et al (2017) Diagnostic Value of Technetium-99m Bone Scintigraphy in the Detection of Cervical Spine Metastases in Oncological Patients. Spine 42(22): 1699–1705 [PubMed: 28368988]	Population – does not match protocol
Park, Sun-Won, Lee, Joo-Hyuk, Ehara, Shigeru et al (2004) Single shot fast spin echo diffusion-weighted MR imaging of the spine; Is it useful in differentiating malignant metastatic tumor infiltration from benign fracture edema?. Clinical imaging 28(2): 102–8 [PubMed: 15050221]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Park, Sunghoon, Yoon, Joon-Kee, Chung, Nam-Su et al (2018) Correlations between intravoxel incoherent motion diffusion-weighted MR imaging parameters and 18F-FDG PET/CT metabolic parameters in patients with vertebral bone metastases: initial experience. The British journal of radiology 91(1086): 20170889 [PMC free article: PMC6223291] [PubMed: 29509489]	Outcomes – do not match protocol
Perrin-Resche, I, Bizais, Y, Buhe, T et al (1993) How does iliac crest bone marrow biopsy compare with imaging in the detection of bone metastases in small cell lung cancer?. European journal of nuclear medicine 20(5): 420–5 [PubMed: 8390936]	Population – does not match protocol
Petren-Mallmin, M (1994) Clinical and experimental imaging of breast cancer metastases in the spine. Acta radiologica. Supplementum 391: 1–23 [PubMed: 8172006]	Outcomes – do not match protocol
Petren-Mallmin, M, Nordstrom, B, Andreasson, I et al (1992) MR imaging with histopathological correlation in vertebral metastases of breast cancer. Acta radiologica (Stockholm, Sweden : 1987) 33(3): 213–20 [PubMed: 1591122]	Outcomes – do not match protocol
Pongpornsup, Sopa; Wajanawichakorn, Phromphiang; Danchaivijitr, Nasuda (2009) Benign versus malignant compression fracture: a diagnostic accuracy of magnetic resonance imaging. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 92(1): 64–72 [PubMed: 19260246]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Poulsen, Mads H, Petersen, Henrik, Hoilund-Carlsen, Poul F et al (2014) Spine metastases in prostate cancer: comparison of technetium-99m-MDP whole-body bone scintigraphy, [(18) F]choline positron emission tomography(PET)/computed tomography (CT) and [(18) F]NaF PET/CT. BJU international 114(6): 818–23 [PubMed: 24314065]	Population – does not match protocol
Pozzi, G, Garcia Parra, C, Stradiotti, P et al (2012) Diffusion-weighted MR imaging in differentiation between osteoporotic and neoplastic vertebral fractures. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 21suppl1: 123–7 [PMC free article: PMC3325396] [PubMed: 22411038]	Other protocol criteria - study reported in an included systematic review (Li 2019)
Pozzi, Grazia, Albano, Domenico, Messina, Carmelo et al (2018) Solid bone tumors of the spine: Diagnostic performance of apparent diffusion coefficient measured using diffusion-weighted MRI using histology as a reference standard. Journal of magnetic resonance imaging, 47(4): 1034–1042 [PubMed: 28755383]	Population – does not match protocol
Prabhu, Vikram C, Bilsky, Mark H, Jambhekar, Kedar et al (2003) Results of preoperative embolization for metastatic spinal neoplasms. Journal of neurosurgery 98(2suppl): 156–64 [PubMed: 12650400]	Intervention – does not match protocol
Qi, Na, Meng, Qingyuan, You, Zhiwen et al (2021) Standardized uptake values of 99mTc-MDP in normal vertebrae assessed using quantitative SPECT/CT for differentiation diagnosis of benign and malignant bone lesions. BMC medical imaging 21(1): 39 [PMC free article: PMC7913396] [PubMed: 33639883]	Outcomes – do not match protocol
Qin, Feng, Feng, Yapei, Zhang, Panpan et al (2022) Diagnostic Value of Emission Computed Tomography Combined with Computed Tomography for Metastatic Malignant Tumor of Spine. Contrast media & molecular imaging 2022: 5847589 [PMC free article: PMC9162862] [PubMed: 35685665]	Index test does not match protocol
Reginelli, Alfonso, Silvestro, Giustino, Fontanella, Giovanni et al (2016) Performance status versus anatomical recovery in metastatic disease: The role of palliative radiation treatment. International journal of surgery (London, England) 33suppl1: 126–31 [PubMed: 27353845]	Intervention – does not match protocol
Ren, Hong; Lin, Wei; Ding, Xianjun (2017) Surface Coil Intensity Correction in Magnetic Resonance Imaging in Spinal Metastases. Open medicine (Warsaw, Poland) 12: 138–143 [PMC free article: PMC5471916] [PubMed: 28730173]	Index test - does not match protocol
Runge, V.M., Bradley, W.G., Brant-Zawadzki, M.N. et al (1991) Clinical safety and efficacy of gadoteridol: A study in 411 patients with suspected intracranial and spinal disease. Radiology 181(3): 701–709 [PubMed: 1947085]	Intervention – does not match protocol
Saidha, N K, Ganguly, M, Sidhu, Harkirat Singh et al (2013) The Role of 18 FDG PET-CT in Evaluation of Unknown Primary Tumours. Indian journal of surgical oncology 4(3): 236–41 [PMC free article: PMC3771057] [PubMed: 24426729]	Population – does not match protocol
Savelli, G., Chiti, A., Grasselli, G. et al (2000) The role of bone SPET study in diagnosis of single vertebral metastases. Anticancer Research 20(2b): 1115–1120 [PubMed: 10810405]	Population – does not match protocol
Scarabino, T, Giannatempo, GM, Popolizio, T et al (1996) Fast spin echo imaging of vertebral metastasis: comparison of fat suppression techniques (FSE-CHESS, STIR-FSE). Radiologia medica 92(3): 180–185 [PubMed: 8975299]	Other protocol criteria – not available in English
Schiff, D and O’Neill, B P (1996) Intramedullary spinal cord metastases: clinical features and treatment outcome. Neurology 47(4): 906–12 [PubMed: 8857717]	Outcomes – do not match protocol
Schirrmeister, H, Guhlmann, A, Elsner, K et al (1999) Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 40(10): 1623–9 [PubMed: 10520701]	Population – does not match protocol
Schmidt, GP, Baur, A, Stäbler, A et al (2005) Estimation of diffuse bone marrow infiltration of the spine in multiple myeloma: correlation of MRT with histological results. RoFo 177(5): 745–750 [PubMed: 15871089]	Other protocol criteria – not available in English
Sedonja, I and Budihna, N V (1999) The benefit of SPECT when added to planar scintigraphy in patients with bone metastases in the spine. Clinical nuclear medicine 24(6): 407–13 [PubMed: 10361935]	Outcomes – do not match protocol
Semirgin, S.U. (2019) SPECT/CT findings of suspicious vertebral metastasis on planar bone scintigraphy. Journal of Experimental and Clinical Medicine (Turkey) 36(4): 99–103	Outcomes – do not match protocol
Shah, Lubdha M and Salzman, Karen L (2011) Imaging of spinal metastatic disease. International journal of surgical oncology 2011: 769753 [PMC free article: PMC3263660] [PubMed: 22312523]	Study design – does not match protocol
Sharma, Punit, Dhull, Varun Singh, Reddy, Rama Mohan et al (2013) Hybrid SPECT-CT for characterizing isolated vertebral lesions observed by bone scintigraphy: comparison with planar scintigraphy, SPECT, and CT. Diagnostic and interventional radiology (Ankara, Turkey) 19(1): 33–40 [PubMed: 22865157]	Index test – does not match protocol
Simsek, D.H., Sanli, Y., Civan, C. et al (2020) Does bone scintigraphy still have a role in the era of 68 Ga-PSMA PET/CT in prostate cancer?. Annals of Nuclear Medicine 34(7): 476–485 [PubMed: 32394269]	Population – does not match protocol
Sugimura, K, Kajitani, A, Okizuka, H et al (1991) Assessing response to therapy of spinal metastases with gadolinium-enhanced MR imaging. Journal of magnetic resonance imaging : JMRI 1(4): 481–4 [PubMed: 1665094]	Population – does not match protocol
Sung, Jin Kyeong, Jee, Won-Hee, Jung, Joon-Yong et al (2014) Differentiation of acute osteoporotic and malignant compression fractures of the spine: use of additive qualitative and quantitative axial diffusion-weighted MR imaging to conventional MR imaging at 3.0 T. Radiology 271(2): 488–98 [PubMed: 24484060]	Other protocol criteria - study reported in an included systematic review (Suh 2018)
Tabotta, Flavian, Jreige, Mario, Schaefer, Niklaus et al (2019) Quantitative bone SPECT/CT: high specificity for identification of prostate cancer bone metastases. BMC musculoskeletal disorders 20(1): 619 [PMC free article: PMC6933900] [PubMed: 31878904]	Population – does not match protocol
Tadros, M.Y. and Louka, A.L. (2016) Discrimination between benign and malignant in vertebral marrow lesions with diffusion weighted MRI and chemical shift. Egyptian Journal of Radiology and Nuclear Medicine 47(2): 557–569	Other protocol criteria - study reported in an included systematic review (Suh 2018)
Tan, D Y L; Tsou, I Y Y; Chee, T S G (2002) Differentiation of malignant vertebral collapse from osteoporotic and other benign causes using magnetic resonance imaging. Annals of the Academy of Medicine, Singapore 31(1): 8–14 [PubMed: 11885502]	Other protocol criteria - study reported in an included systematic review (Thawait 2012)
Tan, Hui, Xu, Hui, Luo, Feifei et al (2019) Combined intravoxel incoherent motion diffusion-weighted MR imaging and magnetic resonance spectroscopy in differentiation between osteoporotic and metastatic vertebral compression fractures. Journal of orthopaedic surgery and research 14(1): 299 [PMC free article: PMC6727483] [PubMed: 31488174]	Index test – does not match protocol
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Evidence reviews for investigations – diagnosis

Investigations - diagnosis

Review question

Introduction

Summary of the protocol

Table 1

Methods and process

Diagnostic evidence

Included studies

Test and treat studies

Diagnostic test accuracy studies

Excluded studies

Summary of included studies

Table 2

Summary of the evidence

Screening MRI verses no screening MRI

MSCC hotline verses usual care

Chemical shift MRI for the differential diagnosis of malignant and non-malignant vertebral bone marrow lesions

FDG-PET for the differential diagnosis of malignant and non-malignant vertebral compression fractures

Chemical shift MRI for the differential diagnosis of malignant and non-malignant vertebral compression fractures

Conventional MRI sequences(with or without DWI) for the differential diagnosis of malignant and non-malignant vertebral compression fractures

Tests for diagnosis of metastatic spinal cord compression

Economic evidence

Included studies

Excluded studies

The committee's discussion and interpretation of the evidence

The outcomes that matter most

The quality of the evidence

Benefits and harms

Radiologist involvement

MRI assessment

Other imaging techniques for diagnosis and management

Cost effectiveness and resource use

Recommendations supported by this evidence review

References – included studies

Diagnostic

Appendices

Appendix A. Review protocols

Appendix B. Search strategy (clinical/economic)

Appendix C. Effectiveness evidence study selection

Appendix D. Evidence tables

Appendix E. Forest plots

Appendix F. GRADE and modified GRADE tables

Appendix G. Economic evidence study selection

Study selection for: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Appendix H. Economic evidence tables

Economic evidence tables for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Appendix I. Economic model

Economic model for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Appendix J. Excluded studies

Excluded studies for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Excluded diagnostic studies

Table 10

Excluded economic studies

Appendix K. Research recommendations – full details

Research recommendations for review question: How effective are radiological imaging techniques in the diagnosis of spinal metastases, direct malignant infiltration of the spine or associated spinal cord compression?

Appendix L. Study data - diagnostic accuracy

Table 1Summary of the protocol (PIRTO table)

Table 2Summary of included studies.

Table 10Excluded studies and reasons for their exclusion