Management of asymptomatic spinal metastases
Uitgangsvraag
Key question
What is the recommended strategy for using radiotherapy in patients with asymptomatic spinal metastases to achieve local control and prevent the development of symptoms?
Aanbeveling
Recommendations
- Offer radiotherapy to patients with asymptomatic MESCC at a low threshold if:
- neurological deficits are expected in the short term due to the extent of vertebral destruction and/or epidural extension;
- no systemic therapy with a good probability of response to the asymptomatic MESCC is available or can be administered;
- life expectancy is greater than three months (see also module Assessment of survival prognosis).
- Consider radiotherapy in patients with asymptomatic vertebral metastases without MESCC but with a clinically assessed high risk of developing skeletal-related events (SRE), for example, in the case of a large lytic lesion, if life expectancy is greater than three months.
- For oligometastases, see Table 1 in module Radiotherapy.
- For timeframes, see module Treatment phase – Timelines.
Overwegingen
Considerations
Balance between desired and undesired effects
The treatment of metastatic disease is evolving rapidly. Recent advances in systemic therapies have resulted in an improved prognoses for patients. In parallel with these advances in systemic therapy, the role of local treatments in metastatic disease is also changing at a rapid pace. Whereas local therapies were previously used primarily for palliative symptom relief, they are now increasingly applied as part of an intensive, multimodality approach to patients with metastases. Due to improved survival in patients with metastatic disease, there is a higher likelihood that previously asymptomatic bone metastases will progress to symptomatic spinal metastases. While treating asymptomatic lesions was considered futile due to limited life expectancy, current clinical circumstances may justify a preventive approach in selected cases.
Against this background, one phase II multicenter randomized trial has now been published (Gillespie, 2023). Gillespie and colleagues evaluated the use of prophylactic radiation versus standard of care therapy in 78 patients with high-risk but asymptomatic bone metastases; 31% of the trial population had lesions in the junctional spine. Given that spinal metastases are similar to non-spine bone metastases in terms of bone involvement and pain relief after conventional radiotherapy (Howell, 2013; Hovenier 2025), the working group deems the trial pertinent to this guideline. In the Gillespie trial, high-risk lesions were defined as bulky site of disease in bone (≥2 cm), disease involving the hip, shoulder, or sacroiliac joints, disease in long bones occupying 1/3-2/3 of the cortical thickness, and disease in vertebrae of the junctional spine and/or disease with posterior element involvement. Patients with more than five lesions were enrolled, thus a different population from the oligometastatic patients who have been the main focus of metastasis-directed therapy. The primary end point of the Gillespie trial was frequency of skeletal-related events (SRE), defined as pathologic fractures, spinal cord compression, or orthopedic surgery to bone and/or palliative radiation therapy for pain. Importantly, 90% of the patients in both arms were planned for systemic therapy, and 49-51% in both arms were prescribed bone-modifying agents including bisphosphonates and denosumab. At 1 year, SREs only occurred in 1.6% of patients in the radiation arm compared with 29% in the standard of care arm (P < .001). These reductions in SRE, in turn, likely led to lower rates of hospitalizations, and interestingly, median OS was also significantly improved in the prophylactic radiation group, which was 1.7 years compared with 1 year in the standard of care group. Of note, the Karnofsky Performance Status was not completely balanced between the two groups, with 62% of the patients in the prophylactic radiotherapy arm having a KPS or >90 versus 46% in the observation arm. The extent of visceral metastases and other co-morbid conditions were not reported, which could have an impact on survival in patients with advanced malignancies. These factors might explain, in part, the better survival in the prophylactic radiotherapy arm. Prophylactic radiation also led to a reduction in subsequent pain, but not global quality of life (defined by the EQ-5D-5L composite score), which is potentially explained by the difficulty in detecting (small) differences with local treatment when using global QOL scales, particularly in the setting of widespread disease. When removing SREs related to palliative radiation (i.e., including only pathologic fracture, cord compression, and/or surgical intervention for stability in the definition of SRE), a significant reduction was still observed in the prophylactic radiotherapy arm (12% versus 0%). Because pain alone can affect functional status and morbidity, the investigators would caution against omitting this outcome entirely. Two retrospective cohort studies including patients with asymptomatic bone metastases from breast, prostate or lung cancer also found an association between prophylactic radiation and reduced risk of SRE (Shulman, 2019; Elazab, 2021).
In all three studies, a wide range of dose-fractionation schedules were allowed, including the delivery of 8 Gy in a single fraction, 20 Gy in 5 fractions, and 30 Gy in 10 fractions by conventional radiotherapy, as well as 27 Gy in 3 fractions by stereotactic radiotherapy. SBRT may be especially suitable for patients with good prognosis who live long enough to see this potential long-term benefit in local tumor control but can be contraindicated in certain situations due to fear of SBRT-induced iatrogenic fractures, both in spine and non-spine bone metastases. In addition, a multifraction regimen may potentially result in better reossification in lytic bone metastasis (Groenen, 2016). The optimal dose-fractionation schedule for asymptomatic bone lesions remains to be defined. Given the heterogeneity present among bone metastases, a pragmatic approach may however be advocated in which trials rather will investigate whether any radiation is effective in the asymptomatic setting.
For patients with asymptomatic (or radiologic) spinal cord compression, no randomized trials were found specifically including patients with spinal cord compression, although these patients could participate in the Gillespie trial (Gillespie, 2023). Several studies have reported (high) local control rates after radiotherapy for spinal metastases with epidural involvement, but most studies included patients with symptomatic lesions (Rades, 2011; Rades, 2020; Guckenberger, 2024). A small phase I trial (Ghia, 2025) relaxing the spinal cord constraint when using single fraction spine SBRT, included 32 inoperable patients with thoracic metastatic epidural spinal cord compression with minimal symptomatic lesions (motor strength >4 out of 5). Patients with radiosensitive tumors were excluded, and patients were seen with a history, physical, and neurologic assessment for follow-up every 3 months for 2 years, then every 6 months thereafter with MRI scans of the spine. The 2-year local control was 80%, and in the high-cord Dmax cohorts, the 2- and 5-year local control was 93%. No cases of radiation myelopathy were reported. The UK PROMPTS trial (Dearnaley, 2022) showed that radiotherapy was efficacious in preventing progression of radiological spinal cord compression to symptomatic spinal cord compression. In this trial, radiotherapy was given to 50 sites of radiological spinal cord compression, with patients mostly receiving 20 Gy in 5 fractions. Protocol-defined follow-up MRI was done in 32 patients: 57% had improved epidural spinal cord compression scores, 39% lesions were stable, and only 4% of the lesions had progressed.
A key aspect for future implementation research will be identification of patients at high risk of developing SREs. A clear definition of high-risk bone metastases still needs to be established, as relying solely on the inclusion criteria used by Gillespie and colleagues may be insufficient. Gillespie and colleagues did not standardize screening imaging in their trial, but instead leveraged imaging scans that had been acquired as part of routine clinical care. Among those enrolled in the trial, 26 patients (33%) were identified by their medical oncologist and had no previous radiotherapy; the remaining 52 patients (67%) were identified for trial enrollment by their radiation oncologist. Interestingly, in patients with castration-resistant prostate cancer, the earlier mentioned UK PROMPTS trial found that the use of screening spinal MRI and pre-emptive treatment of radiological spinal cord compression non-significantly reduced the occurrence of clinical spinal cord compression from 6.7% versus 4.3% at 1 year (Dearnaley, 2022), and the investigators concluded that the routine use of screening MRI is not warranted in patients with castration-resistant prostate cancer. Of note, the low rates of neurological impairment suggest that patients in both the intervention and control groups might have benefitted from trial participation. By considering patients for participation in the Gillespie trial, physicians are likely already applying an implicit assessment of high-risk metastases based on their experience and clinical knowledge; however, explicitly defining the criteria underlying this selection is essential both to promote uniformity of care and to advance scientific understanding (the natural course) of bone metastases.
In high risk patients, prophylactic radiation represents a well-tolerated, low-cost intervention that likely offers substantial benefit for patients and reduces medical costs in the long term through avoidance of SREs and hospitalizations. The significant morbidity benefit and minimal toxicity associated with radiotherapy are likely enough reasons to consider routinely offering such an intervention, but the working group is eagerly awaiting the results of three ongoing phase III randomized trials that may provide further data on prophylactic radiotherapy of asymptomatic or minimally symptomatic bone metastasis: the HERMES trial, the PROMISSeD trial (Rothrock,2024), and the NCT05351294.
It should be noted that, in writing these considerations, we have not included studies investigating oligometastatic or oligoprogressive lesions, which are often asymptomatic, as these trials often primarily focus on outcomes such as progression free or overall survival which may vary substantially by primary tumor.
Quality of the evidence
The overall quality of the evidence is very low. This means that we are very uncertain about the estimated effect size regarding skeletal-related events. The certainty of the evidence is downgraded due to the lack of blinding and differences in the studied populations (bone metastases instead of specifically vertebral metastases).
Values and preferences of patients (and possibly their relatives/caregivers)
Even if the scientific evidence for the treatment is weak, there may still be considerable potential benefit for the individual patient. The advantage of irradiating an asymptomatic lesion is a reduced risk of developing an SRE. Patients place high value on maintaining mobility and autonomy, which can be adversely affected by an SRE. The drawback for the patient is the additional burden of radiotherapy. In many cases, the asymptomatic lesion will be irradiated if the patient is already being treated for a symptomatic lesion. There may also be short-term additional side effects depending on the location of the metastasis. In a shared decision-making conversation, the potential benefit must always be weighed against the additional burden and possible side effects, together with the patient and their relatives. Depending on the type of radiation, apart from a planning CT for radiotherapy planning, no additional preparation is required, and treatment can usually take place at most radiotherapy departments in the Netherlands within a few days after consultation. In the case of more complex radiation such as SBRT, additional examinations may be necessary, such as an extra MRI scan or fitting of a vacuum mattress.
Cost aspects
Local treatment by means of radiotherapy incurs costs, with stereotactic radiotherapy being more expensive than conventional treatment. It can be argued, however, that preventing morbidity is cost-saving. In the context of the total costs of treating an oncology patient, the working group does not expect this treatment to significantly increase overall expenses.
Radiotherapy is a relatively inexpensive treatment. Literature shows a cost reduction in patients who underwent preventive surgery of the femur compared to patients who actually suffered a fracture (Willeumier, 2018). It is uncertain whether this also applies to preventive radiotherapy. There may also be overtreatment, and it is unclear whether it is cost-effective for the larger group of patients, since the number needed to treat (asymptomatic patients with high-risk vertebral metastases) is unknown. No formal cost studies have been reported in the NICE guideline or in the literature.
The dissertation of Floris van Tol (Van Tol, 2022; Van Tol, 2020; Van Tol, 2019) also shows that patients with (severe) neurological deficits have worse clinical outcomes, and at higher costs.
Equity (health equity/equitable)
There are no indications that inequality in access to care or care coordination plays a role for patients with vertebral metastases. The working group assumes that every patient is entitled to the same quality of coordination and follow-up, regardless of background or treatment location.
Acceptability
Ethical acceptability
There are no known ethical objections. The decision whether to irradiate an asymptomatic vertebral metastasis should be made in close consultation between the patient, their relatives, and the treating physician(s), carefully weighing all potential benefits and drawbacks.
Sustainability
Sustainability considerations do not play a role in this intervention.
Feasibility
The exact number of asymptomatic patients with high-risk vertebral metastases per year is not known, but this treatment can be provided in all radiotherapy centers. As noted, a substantial proportion of patients are already receiving radiotherapy; in such cases, the irradiation of an additional asymptomatic lesion represents an extension of existing practice. This is already routinely performed in current clinical settings.
Onderbouwing
Background
The most serious complications of bone metastases are skeletal-related events (SREs), which are defined as pathological fractures, spinal cord compression, pain, or other symptoms necessitating urgent medical interventions such as surgery or radiotherapy. If not promptly recognized and treated, spinal cord compression can result in paraplegia, sensory neuropathies, and dysfunction of the bladder or bowel.
SREs are frequently observed in patients with bone metastases originating from solid tumors, with incidence rates ranging from 45% to 65% in those not receiving prophylactic bone modifying agents (Coleman, 2020). Although bone-targeted agents such as denosumab and bisphosphonates have been shown to significantly reduce the incidence of SREs, they still occur in over 30% of patients despite treatment.
Given the substantial negative impact of SREs on patients’ quality of life, there remains an unmet clinical need for more effective preventive strategies. Radiotherapy is a well-established palliative intervention for uncomplicated metastatic bone pain; however, it is typically administered only after the onset of symptoms. In theory, applying radiotherapy to asymptomatic lesions could lower the risk of future SREs. The central challenge lies in identifying which patients and which high-risk lesions may benefit most from prophylactic radiotherapy.
Summary of Findings
Radiotherapy compared to no radiotherapy for asymptomatic spinal metastases
Population: Patients with asymptomatic spinal metastases
Intervention: Radiotherapy
Comparator: No radiotherapy
|
Outcome |
Study results and measurements |
Absolute effect estimates |
Certainty of the Evidence (Quality of evidence) |
Conclusions |
|
|
Radiotherapy |
No radiotherapy |
||||
|
Skeletal related events (critical)
|
Hazard ratio: 0.09 (CI 95% 0.01 – 0.66) Based on data from 78 participants in 1 study
|
1/62 bone metastases (1.6%) |
14/49 bone metastases (29%) |
Very low Due to serious risk of bias1, due to serious indirectness2 |
The evidence is very uncertain about the effect of radiotherapy on skeletal related events when compared with no radiotherapy in patients with asymptomatic spinal metastases. (Gillespie 2023) |
|
Difference: P<0.001 (CI 95% not reported) |
|||||
|
Overall survival (important)
|
Hazard ratio: 0.46 (CI 95% 0.25 – 0.83) Based on data from 78 participants in 1 study
|
(Median in years) 1.7 (1.3-NR) |
(Median in years) 1.0 (0.8-1.9) |
Very low Due to serious indirectness2, due to serious imprecision3 |
The evidence is very uncertain about the effect of radiotherapy on overall survival when compared with no radiotherapy in patients with asymptomatic spinal metastases. (Gillespie 2023) |
|
Difference: P<0.001 (CI 95% not reported) |
|||||
|
Quality of life (important) |
-
|
Measured by EQ-5D-5L: not significant different between study arms at baseline, 3, 6 and 12 months.
Based on data from 78 participants in 1 study |
Very low Due to serious risk of bias1, due to serious indirectness2, due to serious imprecision3 |
The evidence is very uncertain about the effect of radiotherapy on quality of life when compared with no radiotherapy in patients with asymptomatic spinal metastases. (Gillespie 2023) |
|
|
Local control (important)
|
- |
- |
- |
No evidence was found regarding the effect of radiotherapy when compared with no radiotherapy in patients with asymptomatic spinal metastases |
|
|
Pain relief (important)
|
- |
Measured by Brief Pain Inventory Significant difference in the trajectory at 12 months (–2.0; 95% CI: –3.9 to–0.1) p=0 .039
Based on data from 78 participants in 1 study |
Very low Due to serious risk of bias1, due to serious indirectness2, due to serious imprecision3 |
The evidence is very uncertain about the effect of radiotherapy on pain relief when compared with no radiotherapy in patients with asymptomatic spinal metastases. (Gillespie 2023) |
|
1. Risk of Bias: serious. Due to lack of blinding
2. Indirectness: serious. Due to indirectness in population (Downgraded by two levels).
3. Imprecision: serious. Due to overlap of the upper limit of the 95% confidence interval with the minimal clinically important difference.
Summary of literature
Description of studies
A total of one study was included in the analysis of the literature. Important study characteristics and results are summarized in Table 2. The assessment of the risk of bias is summarized in the risk of bias table (under the tab ‘Appendices’).
Table 2. Characteristics of included studies
|
Study |
Participants |
Comparison |
Follow-up |
Outcome measures and effect size |
RoB/Comments |
|
Gillespie, 2023 |
Patients With High-Risk Asymptomatic Bone Metastases: High risk was defined as (1) bulky site of disease in bone (≥2 cm); (2) disease involving the hip (acetabulum, femoral head, and femoral neck), shoulder (acromion, glenoid, and humeral head), or sacroiliac joints; (3) disease in long bones occupying one third to two third of the cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, and phalanges); (4) disease in vertebrae of the junctional spine (C7-T1, T12-L1, and L5-S1) and/or disease with posterior element involvement. Additional eligibility criteria: 1) Eastern Cooperative Oncology Group performance status ≤2. 2) Patients were eligible to enroll on opioids if it was not prescribed for the index bone metastasis(es). Exclusion criteria: 1) The presence of more than five metastatic lesions was required because of competing trials. 2) Patients with complicated bone metastases as previously defined, those requiring prophylactic stabilization surgery, or those who had received previous radiation to the index bone metastasis(es) were ineligible.
N at baseline Intervention: n=38/39, 62 bone metastases Control: n=37/39, 49 bone metastases
Age (mean, SD) Intervention: median (IQR) 64 (59-72) Control: median (IQR) 65 (60-73)
Sex Intervention: Male: 18 (46%) Control: Male: 22 (56%) [other relevant characteristics] |
Intervention: prophylactic radiotherapy
Control: systemic therapy or observation
|
1-year for SRE 2.5 year for survival
|
The primary objective: SRE, defined as pathologic fractures, spinal cord compression, orthopedic surgery to bone, and/or palliative RT for pain.
Secondary objectives: Overall survival (OS), opioid-free survival (among those not on opioids at baseline).
Patient-reported outcomes included pain level measured with BPI and quality of life measured with EQ-5D-5L. |
Risk of bias*: Some concerns Low for overall survival
Funding: in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) through Cancer Center Support Grant No. P30 CA008748 (Memorial Sloan Kettering) and NCI Career Development Award No. K08 CA252640 (E.F.G.).
There are some conflicts of interest disclosure.
|
*For further details, see risk of bias table
Results
Gillespie 2023 reported the outcome of SRE, overall survival, pain level, and quality of life (Table 3).
Table 3. Results per outcome
|
Outcomes |
Radiotherapy (n=39) |
Control (N=39) |
Difference |
HR (95%CI) |
|
SRE |
1/62 (1.6%) bone metastases |
14/49 (28.6%) bone metastases |
P<0.001 |
0.09 (0.01-0.66) P= 0.018
|
|
Overall survival (median in years) |
1.7 (1.3-NR) |
1.0 (0.8-1.9) |
P=0.018
|
0.46 (0.25-0.83) |
|
Pain level
|
Significant difference in the trajectory at 12 months (–2.0; 95% CI: –3.9 to–0.1) p=0 .039 |
|||
|
Quality of life |
No significant difference at any time point |
|||
SRE was defined as pathologic fractures, spinal cord compression, orthopedic surgery to bone, and/or palliative RT for pain.
Search and select
A systematic review of the literature was performed to answer the following question(s):
What are the benefits and risks of radiotherapy compared with watchful waiting for patients with asymptomatic spinal metastases?
Table 1. PICO
| Patients | Patients with asymptomatic spinal metastases |
| Intervention | Radiotherapy |
| Control | Standard of care |
| Outcomes | Skeletal related events (defined as pathological fractures, spinal cord compression, pain, or other symptoms necessitating urgent medical interventions such as surgery or radiotherapy), local tumor control, pain relief, quality of life, overall survival |
| Other selection criteria | Study design: systematic reviews and randomized controlled trials |
Relevant outcome measures
The guideline panel considered SREs as a critical outcome measure for decision making; and local tumor control, pain relief, quality of life, and overall survival as an important outcome measure for decision making.
Definitions and thresholds
|
Outcome |
Definition |
Threshold |
|
SRE (critical outcome measure) |
Including fractures, MSCC, local intervention required, as defined in the used studies |
Relative ratio ≥1.25 or ≤0.80 |
|
Local control (important outcome measure) |
As defined in the used studies |
Relative ratio ≥1.25 or ≤0.80 |
|
Overall survival (important outcome measure) |
As defined in the used studies |
HR: 0.7/1.4; 12/16 week depending on life of expectancy
|
|
Pain relief/pain response (important outcome measure) |
As defined in the used studies |
20% (i.e. 2 points decrease on NRS (0-10) scale) |
|
Quality of life (important outcome measure) |
As defined in the used studies |
EQ-5D: >0.08 points EQ-5D VAS: > 7 points (Pickard, 2007) |
Search and select (Methods)
A systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline. Both databases were searched from January 1st, 2021 (which was the cutoff year of the recent NICE guideline search) to January 24th, 2025 for systematic reviews and randomized trials. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. The overall search strategy was derived from two primary search concepts: (1) asymptomatic spinal metastases; (2) radiotherapy. Duplicates were removed using EndNote software. After deduplication a total of 45 records were imported for title/abstract screening. Initially, nine studies were selected based on title and abstract screening. After reading the full text, eight studies were excluded (see the exclusion table under the tab ‘Appendices’), and one study was included.
- 1 - Coleman RE, Brown J, Holen I. Bone metastases. Abeloff's clinical oncology. 2020 Jan 1:809-30.
- 2 - Dearnaley D, Hinder V, Hijab A, Horan G, Srihari N, Rich P, Houston JG, Henry AM, Gibbs S, Venkitaraman R, Cruickshank C. 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. The Lancet Oncology. 2022 Apr 1;23(4):501-13.
- 3 - Elazab SH, Elkalla HM, Zahi MS. Palliative Radiotherapy to Asymptomatic Bone Metastasis: Is It Beneficial or Not? Single Institution Experience. Middle East Journal of Cancer. 2021 Jul 1;12(3):422-8.
- 4 - Ghia AJ, Guha-Thakurta N, Munsell MF, Briere TM, Wang C, Beckham TH, Yeboa D, Tom MC, Perni S, Li J, McAleer M. Long-term results from a Phase 1 study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery in the primary management of patients with inoperable, previously unirradiated spinal metastases with epidural extension. International Journal of Radiation Oncology* Biology* Physics. 2025 Jul 2.
- 5 - Gillespie EF, Yang JC, Mathis NJ, Marine CB, White C, Zhang Z, Barker CA, Kotecha R, McIntosh A, Vaynrub M, Bartelstein MK. Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: a multicenter, randomized phase II clinical trial. Journal of Clinical Oncology. 2024 Jan 1;42(1):38-46.
- 6 - Groenen KH, Pouw MH, Hannink G, Hosman AJ, van der Linden YM, Verdonschot N, Tanck E. The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review. Radiotherapy and Oncology. 2016 May 1;119(2):194-201.
- 7 - Guckenberger M, Billiet C, Schnell D, Franzese C, Spałek M, Rogers S, Stelmes JJ, Aebersold DM, Hemmatazad H, Zimmermann F, Zimmer J. Dose‐intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial. Cancer. 2024 Aug 1;130(15):2713-22.
- 8 - Howell DD, James JL, Hartsell WF, Suntharalingam M, Machtay M, Suh JH, Demas WF, Sandler HM, Kachnic LA, Berk LB. Single‐fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases—equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97‐14. Cancer. 2013 Feb 15;119(4):888-96.
- 9 - Howell DD, James JL, Hartsell WF, Suntharalingam M, Machtay M, Suh JH, Demas WF, Sandler HM, Kachnic LA, Berk LB. Single‐fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases—equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97‐14. Cancer. 2013 Feb 15;119(4):888-96.
- 10 - Rades D, Lange M, Veninga T, Stalpers LJ, Bajrovic A, Adamietz IA, Rudat V, Schild SE. Final results of a prospective study comparing the local control of short-course and long-course radiotherapy for metastatic spinal cord compression. International Journal of Radiation Oncology* Biology* Physics. 2011 Feb 1;79(2):524-30.
- 11 - Rades D, Cacicedo J, Conde-Moreno AJ, Segedin B, But-Hadzic J, Groselj B, Kevlishvili G, Lomidze D, Ciervide-Jurio R, Rubio C, Perez-Romasanta LA. Precision radiation therapy for metastatic spinal cord compression: Final results of the PRE-MODE Trial. International Journal of Radiation Oncology* Biology* Physics. 2020 Mar 15;106(4):780-9.
- 12 - Rothrock RJ, Ozair A, Avendano MC, Herrera S, Appel H, Ramos S, Starosciak AK, Leon-Ariza DS, Rubens M, McDermott MW, Ahluwalia MS. Prophylactic Radiotherapy Of MInimally Symptomatic Spinal Disease (PROMISSeD): study protocol for a randomized controlled trial. Trials. 2024 Jan 12;25(1):41.
- 13 - Shulman RM, Meyer JE, Li T, Howell KJ. External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs). Annals of palliative medicine. 2019 Apr;8(2):15967-167.
- 14 - van Tol FR, Massier JR, Frederix GW, Öner FC, Verkooijen HM, Verlaan JJ. Costs associated with timely and delayed surgical treatment of spinal metastases. Global Spine Journal. 2022 Oct;12(8):1661-6.
- 15 - van Tol FR, Suijkerbuijk KP, Choi D, Verkooijen HM, Oner FC, Verlaan JJ. The importance of timely treatment for quality of life and survival in patients with symptomatic spinal metastases. European Spine Journal. 2020 Dec;29(12):3170-8.
- 16 - van Tol FR, Choi D, Verkooijen HM, Oner FC, Verlaan JJ. Delayed presentation to a spine surgeon is the strongest predictor of poor postoperative outcome in patients surgically treated for symptomatic spinal metastases. The Spine Journal. 2019 Sep 1;19(9):1540-7.
- 17 - Willeumier JJ, van der Wal CG, Schoones JW, van der Wal RJ, Dijkstra PS. Pathologic fractures of the distal femur: current concepts and treatment options. Journal of surgical oncology. 2018 Nov;118(6):883-90.
Evidence tables
Risk of bias Table (randomized controlled trials; based on Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University)
Research question: What are the benefits and risks of radiotherapy compared with watchful waiting for patients with asymptomatic spinal metastases?
|
Study reference
(first author, publication year) |
Was the allocation sequence adequately generated?
Definitely yes Probably yes Probably no Definitely no |
Was the allocation adequately concealed?
Definitely yes Probably yes Probably no Definitely no |
Blinding: Was knowledge of the allocated interventions adequately prevented?
Were patients blinded?
Were healthcare providers blinded?
Were data collectors blinded?
Were outcome assessors blinded?
Were data analysts blinded?
Definitely yes Probably yes Probably no Definitely no |
Was loss to follow-up (missing outcome data) infrequent?
Definitely yes Probably yes Probably no Definitely no |
Are reports of the study free of selective outcome reporting?
Definitely yes Probably yes Probably no Definitely no |
Was the study apparently free of other problems that could put it at a risk of bias?
Definitely yes Probably yes Probably no Definitely no |
Overall risk of bias If applicable/necessary, per outcome measure
LOW Some concerns HIGH |
|
Gillespie, 2023 |
Probably yes
Reason: Patients were randomly assigned in a 1:1 ratio using permuted blocks to either standard of care (SOC) or RT to all enrolled high-risk bone metastases.
|
Probabl yes
Reason: Patients were stratified by primary disease histology (breast or prostate cancer v other) and planned SOC (systemic therapy v observation).
|
Definitely no
Reason: There was no blinding of patients or physicians.
|
Probably yes
Reason: The reason of exclusion after randomization was listed. The exclusion rate is likey reasonable.
|
Probably yes
Reason: All relevant outcomes were reported.
|
Probably yes
Reason: No other problems noted. |
Some concerns (No blinding)
Some concerns for SRE, pain level, and quality of life
Low for overall survival given that survival or not is an objective outcome.
|
Table of excluded studies
|
Reference |
Reason for exclusion |
|
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 |
Wrong comperison |
|
Prophylactic Radiotherapy Of MInimally Symptomatic Spinal Disease (PROMISSeD): study protocol for a randomized controlled trial |
Study protocol |
|
Palliative radiotherapy to asymptomatic bone metastasis: Is it beneficial or not? single institution experience |
Observational study |
|
The role of combination surgery and radiotherapy in patients with metastatic spinal cord compression: What are the remaining grey areas? A systematic review |
Symptomatic spinal metastasis |
|
Time to Pain Relapse After Palliative Radiotherapy for Bone Metastasis: A Prospective Multi-institutional Study |
Wrong comperison |
|
The Identification of Risk Factors for Symptomatic Spinal Metastasis Onset: A Prospective Cohort Study of 128 Asymptomatic Spinal Metastasis Patients |
Symptomatic spinal metastasis |
|
[Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases] |
Comment for Gillespie 2024 |
|
PROMPTS Trial: Screening spinal magnetic resonance imaging in castration-resistant prostate cancer |
Study protocol |
Beoordelingsdatum en geldigheid
Publicatiedatum : 05-06-2026
Beoordeeld op geldigheid : 05-06-2026
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2023 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met wervelmetastasen.
Werkgroep
- dr. W. (Walter) Taal (voorzitter), neuroloog Erasmuc MC, Nederlandse Vereniging voor Neurologie
- drs. L. (Lena) van Iterson, AIOS-neuroloog Elisabeth-TweeSteden Ziekenhuis, Nederlandse Vereniging voor Neurologie
- drs. R.P.B. (Robin) Boltjes, neuroloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Neurologie
- Prof. dr. JJ. (Jorrit-Jan) Verlaan, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. J. (Jasper) van Tiel, Orthopedisch chirurg UMC Utrecht, Nederlandse Orthopaedische Vereniging
- dr. V. (Vivian) Bongers, Nucleaire geneeskunde Diakonessenhuis Utretch, Nederlandse Vereniging voor Nucleaire Geneeskunde
- Prof. dr. R. (Ronald) Bartels, Neurochirurg Radboudumc, Nederlandse Vereniging voor Neurochirurgie
- dr. S.O. (Selma) Algra, Radioloog UMC Utrecht, Nederlandse Vereniging voor Radiologie
- drs. M.G.A. (Maaike) Schippers, radiotherapeut Instituut Verbeeten, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. J.M. (Joanne) van der Velden, radiotherapeut UMC Utrecht, Nederlandse Vereniging voor Radiotherapie en Oncologie
- dr. M.S. (Marthe) Paats, longarts Erasmus MC, Nederlandse Vereniging voor Artsen voor Longziekten en TBC
- dr. P.F. (Paula) Ypma, Internist hematoloog Haga Ziekenhuis, Nederlandse Internisten Vereniging
- dr. F.Y.F.L. (Filip) de Vos, internist-oncoloog en kaderarts palliatieve zorg UMC Utrecht, Nederlandse Internisten Vereniging
- dr. M. (Marije) Vos- van der Hulst, revalidatiearts Sint Maartenskliniek, Nederlandse Vereniging van Revalidatieartsen (vanaf oktober 2025)
- Mevr. S (Silvie) Dronkers†, patiëntvertegenwoordiger, Stichting Darmkanker (tot oktober 2025)
- dr. T.A.R. (Tebbe) Sluis†, Revalidatiearts Rijndam, Nederlandse Vereniging van Revalidatieartsen (tot mei 2025)
Klankbordgroep
- Mevr. Manon Immerzeel, Verpleegkundig specialist Reinier de Graaf ziekenhuis, Verpleegkundigen en Verzorgenden Nederland
- drs. A. (Anita) Ophof, anesthesioloog Antoni van Leeuwenhoek Ziekenhuis, Nederlandse Vereniging voor Anesthesiologie
Met dank aan
- dr. J.H. (Jurgen) Runge, interventieradioloog, UMC Groningen, Nederlandse Vereniging voor Radiologie
Met ondersteuning van
- dr. J. (Josefien) Buddeke, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (vanaf juli 2024)
- dr. L. (Linda) Oostendorp, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot juli 2024)
- drs. B. (Beatrix) Vogelaar, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- dr. J. (Jing) de Haan-Du, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. D. (Danique) Middelhuis, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
- drs. A. (Alies) Oost, informatiespecialist, Kennisinstituut van de Federatie Medisch Specialisten
Belangenverklaringen
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.
Gemelde (neven)functies en belangen werkgroep
|
Naam WERKGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Jasper van Tiel |
Orthopedisch chirurg UMC Utrecht en Acibadem IMC |
geen |
geen |
geen |
geen |
geen |
geen |
22-11-2023 |
Geen restrictie |
|
Joanne van der Velden |
Radiotherapeut bij het UMC Utrecht, betaald |
Bestuurslid bij het Landelijk Platform Palliatieve Radiotherapie (NVRO), onbetaald |
Geen |
Geen |
Deelname aan 2 extern gefinancierde onderzoeken, zie onder |
Verwerven van erkenning speelt mee aan mijn deelname aan de werkgroep richtlijn Wervelmetastasen |
Geen overige belangen |
28-12-2023 |
Geen restrictie |
|
Jorrit-Jan Verlaan |
Orthopedisch chirurg, UMC Utrecht (0.4 Fte) |
Lid steering committee AO Spine Knowledge Forum Tumor (onbetaald maar met onkosten vergoeding). |
Hoe de richtlijn wordt vormgegeven staat los van mijn persoonlijke financiële belangen. Er zijn ook geen belangen voor SentryX hoe de richtlijn wordt vormgegeven. |
geen |
Ja. |
Ik heb nationale/internationale expertise/reputatie en een leerstoel op het gebied van de behandeling van wervelmetastasen. Een goed uitgevoerde richtlijn kan helpen deze expertise/reputatie meer exposure te geven maar de impact en eventuele belangenverstrengeling zijn mij onduidelijk. |
geen |
22-11-2023 |
Geen restrictie. Geen penvoerder bij module 'Inschatten overleving'. |
|
Filip de Vos |
Internist-oncoloog en kaderarts palliatieve zorg |
geen |
geen |
geen |
ja |
geen |
BMS Advisory Board; Faculty member ESMO CNS tumors; Quality of Care commission Dutch Society of Medical Oncology; |
20-12-2023 |
Geen restrictie. (In de richtlijn worden geen systemische therapien aanbevolen.) |
|
Maaike Schippers |
Radiotherapeut |
geen |
geen |
geen |
geen |
geen |
geen |
3-12-2023 |
Geen restrictie |
|
Marthe Paats |
Longarts Erasmus MC |
geen |
Geen relevant voor huidige richtlijn. |
geen |
industrie gesponsorde studies lopend in het Erasmus MC waarbij ik lokale PI ben. |
geen |
geen |
26-02-2024 |
Geen restrictie. In de richtlijn worden geen systemische therapien aanbevolen. |
|
Robin Boltjes |
Neuroloog in Antoni van Leeuwenhoek/NKI |
geen |
geen |
nee |
geen |
geen |
nee |
22-11-2023 |
Geen restrictie |
|
Ronald Bartels |
Neurochirurg |
Medisch Adviseur |
geen |
nee |
geen |
net |
geen |
03-04-2024 |
Restrictie ten aanzien van besluitvorming betreffende 'Inschatten overleving'. Vanuit expertise wel meegediscussierd over inhoud van de module, niet betrokken bij het formuleren van de aanbevelingen. |
|
Tebbe Sluis |
revalidatiearts |
geen |
geen |
geen |
geen |
geen |
geen |
11-12-2023 |
Geen restrictie |
|
Vivian Bongers |
MSB Domstad, medisch specialist |
Uitgeverij Prelum, Redacteur tijdschrift IMAGO |
Geen |
Geen |
Geen |
Geen |
Geen |
23-11-2023 |
Geen restrictie |
|
Ypma |
internist hematoloog Hagaziekenhuis den Haag |
geen |
geen |
geen |
Alphabet trial |
geen |
nvt |
04-05-2024 |
Geen restrictie |
|
Van Iterson |
AIOS neurologie |
geen |
geen |
geen |
geen |
geen |
geen |
25-04-2024 |
Geen restrictie |
|
Selma Algra |
Radioloog,St Jansdal Ziekenhuis |
geen |
geen |
geen |
geen |
geen |
geen |
03-09-2024 |
Geen resctrictie |
|
Silvie Dronkers |
Stichting Darmkanker |
geen |
geen |
geen |
geen |
geen |
geen |
06-02-2025 |
Geen restrictie |
|
Walter Taal (voorzitter) |
Neuroloog, Erasmus MC, Rotterdam |
Geen |
Geen |
Geen |
Ja. Alleen op het gebied van neurofibromatose type 1 |
Geen |
Geen |
07-06-2023 |
Geen restrictie |
|
Marije Vos-van der Hulst |
Revalidatie arts, Sint Maartenskliniek Nijmegen |
Voorzitter werkgroep revalidatie artsen dwarslaesie (Nederlands Vlaams dwarslaesie genootschap= werkgroep van de vereniging revalidatieartsen nederland (VRA)) |
geen |
geen |
geen |
geen |
geen |
13-10-2025 |
Geen restrictie |
|
Naam KLANKBORDGROEP |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke Financiele_Belangen |
Persoonlijke Relaties |
Extern Gefinancierd Onderzoek |
Intellectuele Belangen Reputatie |
Overige Belangen |
Datum |
Acties |
|
Manon Immerzeel |
Deelnemer clusterstuurgroep |
Geen |
Geen |
Geen |
Geen |
Voorzitter in het bestuur van V&VN pijnverpleegkundigen |
Neen |
22-03-2022 |
Geen restrictie |
|
Anita Ophof |
Antoni van Leeuwenhoek Ziekenhuis |
Geen |
Geen |
Geen |
Geen |
Geen |
Geen |
01-05-2025 |
Geen restrictie |
Inbreng patiëntenperspectief
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).
De kwalitatieve raming is toegevoegd aan het einde van elke herziene module.
| Module | Uitkomst raming | Toelichting |
| Management of asymptomatic spinal metastases | Geen substantiële financiële gevolgen | Hoewel uit de toetsing volgt dat de aanbevelingen breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.
Zoekverantwoording
Algemene informatie
|
Cluster/richtlijn: NVN Wervelmetastasen |
|
|
Uitgangsvraag/modules: UV12 What are the benefits and risks of radiotherapy compared with watchful waiting for patients with asymptomatic spinal metastases? |
|
|
Database(s): Embase.com, Ovid/Medline all |
Datum: 24 januari 2025 |
|
Periode: vanaf 2021 (NICE RL) |
Talen: geen restrictie |
|
Literatuurspecialist: Alies Oost |
|
|
BMI-zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ |
|
|
Toelichting: Voor deze vraag is gezocht op de elementen:
De sleutelartikelen worden gevonden met deze search. |
|
|
Te gebruiken voor richtlijntekst: A systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline all. Both databases were searched from 2021 to January 24, 2025 for systematic reviews, RCTs and observational studies. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. The overall search strategy was derived from two primary search concepts: (1) asymptomatic spinal metastases; (2) radiotherapy. Duplicates were removed using EndNote software. After deduplication a total of 45 records were imported for title/abstract screening. Initially, XX studies were selected based on title and abstract screening. After reading the full text, XXX studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and XXX studies were included. |
|
Zoekopbrengst
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR |
6 |
4 |
6 |
|
RCT |
13 |
8 |
13 |
|
Observationele studies |
25 |
15 |
26 |
|
Totaal |
44 |
27 |
45* |
*in Rayyan
Zoekstrategie
Embase.com
|
No. |
Query |
Results |
|
#1 |
('spine metastasis'/exp OR 'spinal cord metastasis'/exp OR 'cervical lymph node metastasis'/exp OR (('spinal cord tumor'/exp OR 'spine tumor'/exp OR 'spinal cord compression'/exp OR (((spinal* OR medulla*) NEAR/3 (compress* OR impingement OR pinch*)):ti,ab,kw)) AND ('metastasis'/de OR 'bone metastasis'/de OR metasta*:ti,ab,kw OR oligometasta*:ti,ab,kw OR micrometasta*:ti,ab,kw OR (((neoplas* OR carcinoma OR cancer* OR malignan* OR tumor* OR tumour*) NEAR/4 (dissemination OR disseminated OR spread* OR secondary OR migrat* OR seed*)):ti,ab,kw))) OR (((spine* OR spinal* OR intraspinal OR vertebr* OR 'cauda equina' OR cervicothoracic OR cord* OR coccyx OR duralsac* OR 'dural sac*' OR epidural OR extradural OR 'extra dural' OR intervertebr* OR lumbar OR lumbosac* OR 'lumbo sac*' OR orthothoracic OR sacral OR sacrum OR 'thecal sac*' OR thoracolumbar OR odontoid OR 'anterior horn' OR 'posterior horn' OR 'extrapyramidal tract*' OR 'pyramidal tract*' OR 'substantia gelatinosa' OR 'spinothalamic tract*') NEAR/4 (metast* OR oligometast* OR micrometast*)):ti,ab,kw) OR ((cervical*:ti,ab,kw OR medulla*:ti,ab,kw OR intramedulla*:ti,ab,kw OR thoracic:ti,ab,kw) AND (spine*:ti,ab,kw OR spinal*:ti,ab,kw OR intraspinal:ti,ab,kw OR vertebr*:ti,ab,kw OR intervertebr*:ti,ab,kw OR lumbar:ti,ab,kw) AND (metast*:ti,ab,kw OR oligometast*:ti,ab,kw OR micrometast*:ti,ab,kw)) OR ('bone metastasis'/de AND 'high risk':ti,ab,kw) OR (('bone metast*' NEAR/3 'high risk'):ti,ab,kw) OR mescc:ti,ab,kw OR mscc:ti,ab,kw) AND ('asymptomatic disease'/de OR 'incidental finding'/exp OR asymptom*:ti,ab,kw OR nonsymptom*:ti,ab,kw OR 'non symptom*':ti,ab,kw OR 'no symptom*':ti,ab,kw OR presymptom*:ti,ab,kw OR 'pre symptom*':ti,ab,kw OR subclinical*:ti,ab,kw OR 'sub clinical*':ti,ab,kw OR symptomless:ti,ab,kw OR 'symptom less':ti,ab,kw OR (((incidental* OR accident*) NEAR/3 (find* OR found* OR discover*)):ti,ab,kw)) |
996 |
|
#2 |
'radiotherapy'/exp OR 'radiosurgery'/exp OR 'radiotherap*':ti,ab,kw OR radiosurg*:ti,ab,kw OR 'radio surg*':ti,ab,kw OR irradiati*:ti,ab,kw OR radiati*:ti,ab,kw OR ((bucky NEAR/2 (radiat* OR ray* OR therap* OR treat*)):ti,ab,kw) OR (((radio* OR radiat* OR roentgen OR rontgen) NEAR/2 (therap* OR treat*)):ti,ab,kw) OR 'x radiotherap*':ti,ab,kw OR 'x ray therap*':ti,ab,kw OR 'x ray treatment*':ti,ab,kw OR ((stereotactic NEAR/3 (radiat* OR radio*)):ti,ab,kw) OR sbrt:ti,ab,kw OR sabr:ti,ab,kw OR sabrt:ti,ab,kw OR 'radiofrequency ablation':ti,ab,kw OR 'radio frequency ablation':ti,ab,kw OR 'rf ablation':ti,ab,kw OR rfa:ti,ab,kw |
1440712 |
|
#3 |
#1 AND #2 NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp) |
285 |
|
#4 |
#3 AND [2021-2025]/py |
82 |
|
#5 |
'meta analysis'/exp OR 'meta analysis (topic)'/exp OR 'systematic review'/exp OR 'systematic review (topic)'/exp OR 'scoping review'/exp OR 'rapid review'/exp OR 'umbrella review'/exp OR 'cochrane database of systematic reviews'/jt OR 'network meta-analysis'/exp OR 'networkmeta analy*':ti,ab,kw OR 'networkmetaanaly*':ti,ab,kw OR metaanaly*:ti,ab,kw OR 'meta analy*':ti,ab,kw OR metanaly*:ti,ab,kw OR prisma:ti,ab,kw OR prospero:ti,ab,kw OR metaanali*:ti,ab,kw OR 'meta anali*':ti,ab,kw OR metanali*:ti,ab,kw OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab,kw) OR (((structured OR systemic*) NEAR/3 (review* OR overview* OR synth*) NEAR/3 literature):ti,ab,kw) OR ((systemic* NEAR/1 review*):ti,ab,kw) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab,kw) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab,kw) OR (((literature NEAR/3 (review* OR overview*)):ti,ab,kw) AND (search*:ti,ab,kw OR database*:ti,ab,kw OR 'data base*':ti,ab,kw)) OR (('data extraction*':ti,ab,kw OR 'data source*':ti,ab,kw) AND ('study selection*':ti,ab,kw OR 'studies selection*':ti,ab,kw)) OR ('search strateg*':ti,ab,kw AND 'selection criteria*':ti,ab,kw) OR ('data source*':ti,ab,kw AND 'data synth*':ti,ab,kw) OR medline*:ti,ab,kw OR pubmed*:ti,ab,kw OR 'pub med*':ti,ab,kw OR embase:ti,ab,kw OR cochrane*:ti,ab,kw OR (((critical* OR rapid*) NEAR/2 (review* OR overview* OR synth*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synth*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynth*:ti,ab,kw OR 'meta synth*':ti,ab,kw OR 'review* of review*':ti,ab,kw |
1115808 |
|
#6 |
'clinical trial'/exp OR 'randomization'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp OR 'placebo'/exp OR 'prospective study'/exp OR rct:ab,ti OR random*:ab,ti OR 'single blind':ab,ti OR 'randomised controlled trial':ab,ti OR 'randomized controlled trial'/exp OR placebo*:ab,ti |
4192477 |
|
#7 |
'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('major clinical study'/de OR 'clinical study'/de OR 'cohort analysis'/de OR 'observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab))) |
15739808 |
|
#8 |
'major clinical study'/de OR 'clinical study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'cohort analysis'/de OR 'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti) OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab))) |
17723479 |
|
#9 |
#4 AND #5 |
6 |
|
#10 |
#4 AND #6 NOT #9 |
13 |
|
#11 |
#4 AND (#7 OR #8) NOT (#9 OR #10) |
25 |
|
#12 |
#9 OR #10 OR #11 |
44 |
Ovid/Medline
|
# |
Searches |
Results |
|
1 |
(((exp Spinal Neoplasms/ or exp Spinal Cord Neoplasms/ or exp Spinal Cord Compression/ or ((spinal* or medulla*) adj3 (compress* or impingement or pinch*)).ti,ab,kf.) and (exp Neoplasm Metastasis/ or metasta*.ti,ab,kf. or oligometasta*.ti,ab,kf. or micrometasta*.ti,ab,kf. or ((neoplas* or carcinoma or cancer* or malignan* or tumor* or tumour*) adj4 (dissemination or disseminated or spread* or secondary or migrat* or seed*)).ti,ab,kf.)) or ((spine* or spinal* or intraspinal or vertebr* or 'cauda equina' or cervicothoracic or cord* or coccyx or duralsac* or 'dural sac*' or epidural or extradural or 'extra dural' or intervertebr* or lumbar or lumbosac* or 'lumbo sac*' or orthothoracic or sacral or sacrum or 'thecal sac*' or thoracolumbar or odontoid or "Anterior Horn" or "Posterior Horn" or "Extrapyramidal Tract*" or "Pyramidal Tract*" or "Substantia Gelatinosa" or "Spinothalamic Tract*") adj4 (metast* or oligometast* or micrometast*)).ti,ab,kf. or ((cervical* or medulla* or intramedulla* or thoracic) and (spine* or spinal* or intraspinal or vertebr* or intervertebr* or lumbar) and (metast* or oligometast* or micrometast*)).ti,ab,kf. or ('bone metast*' adj3 'high risk').ti,ab,kf. or mescc.ti,ab,kf. or mscc.ti,ab,kf.) and (Asymptomatic Diseases/ or exp Incidental Findings/ or asymptom*.ti,ab,kf. or nonsymptom*.ti,ab,kf. or 'non symptom*'.ti,ab,kf. or 'no symptom*'.ti,ab,kf. or presymptom*.ti,ab,kf. or 'pre symptom*'.ti,ab,kf. or subclinical*.ti,ab,kf. or 'sub clinical*'.ti,ab,kf. or symptomless.ti,ab,kf. or 'symptom less'.ti,ab,kf. or ((incidental* or accident*) adj3 (find* or found* or discover*)).ti,ab,kf.) |
419 |
|
2 |
exp Radiotherapy/ or 'radiotherap*'.ti,ab,kf. or radiosurg*.ti,ab,kf. or 'radio surg*'.ti,ab,kf. or irradiati*.ti,ab,kf. or radiati*.ti,ab,kf. or (bucky adj2 (radiat* or ray* or therap* or treat*)).ti,ab,kf. or ((radio* or radiat* or roentgen or rontgen) adj2 (therap* or treat*)).ti,ab,kf. or 'x radiotherap*'.ti,ab,kf. or 'x ray therap*'.ti,ab,kf. or 'x ray treatment*'.ti,ab,kf. or (stereotactic adj3 (radiat* or radio*)).ti,ab,kf. or sbrt.ti,ab,kf. or sabr.ti,ab,kf. or sabrt.ti,ab,kf. or 'radiofrequency ablation'.ti,ab,kf. or 'radio frequency ablation'.ti,ab,kf. or 'rf ablation'.ti,ab,kf. or rfa.ti,ab,kf. |
924602 |
|
3 |
(1 and 2) not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/) |
166 |
|
4 |
limit 3 to yr="2021 -Current" |
46 |
|
5 |
exp Meta-Analysis/ or exp "Meta-Analysis as Topic"/ or exp Network Meta-Analysis/ or exp Systematic Review/ or exp "Systematic Reviews as Topic"/ or (networkmeta analy* or networkmetaanaly* or metaanaly* or meta analy* or metanaly* or prisma or prospero or metaanali* or meta anali* or metanali*).ti,ab,kf. or ((systemati* or scoping or umbrella or structured literature) adj3 (review* or overview*)).ti,ab,kf. or ((structured or systemic*) adj3 (review* or overview* or synth*) adj3 literature).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 (review* or overview*)) and (search* or database* or data base*)).ti,ab,kf. or ((data extraction* or data source*) and (study selection* or studies selection*)).ti,ab,kf. or (search strateg* and selection criteria*).ti,ab,kf. or (data source* and data synth*).ti,ab,kf. or (medline* or pubmed* or pub med* or embase or cochrane*).ti,ab,kf. or cochrane.jw. or ((critical* or rapid*) adj2 (review* or overview* or synth*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synth*)) and (search* or database* or data base*)).ab. or metasynth*.ti,ab,kf. or meta synth*.ti,ab,kf. |
808349 |
|
6 |
exp clinical trial/ or randomized controlled trial/ or exp clinical trials as topic/ or randomized controlled trials as topic/ or Random Allocation/ or Double-Blind Method/ or Single-Blind Method/ or (clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter study or clinical trial).pt. or random*.ti,ab. or (clinic* adj trial*).tw. or ((singl* or doubl* or treb* or tripl*) adj (blind$3 or mask$3)).tw. or Placebos/ or placebo*.tw. |
2834724 |
|
7 |
Epidemiologic studies/ or case control studies/ or exp cohort studies/ or Controlled Before-After Studies/ or Case control.tw. or cohort.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective*.tw. or prospective*.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/ [Onder exp cohort studies vallen ook longitudinale, prospectieve en retrospectieve studies] |
4940440 |
|
8 |
Case-control Studies/ or clinical trial, phase ii/ or clinical trial, phase iii/ or clinical trial, phase iv/ or comparative study/ or control groups/ or controlled before-after studies/ or controlled clinical trial/ or double-blind method/ or historically controlled study/ or matched-pair analysis/ or single-blind method/ or (((control or controlled) adj6 (study or studies or trial)) or (compar* adj (study or studies)) or ((control or controlled) adj1 active) or "open label*" or ((double or two or three or multi or trial) adj (arm or arms)) or (allocat* adj10 (arm or arms)) or placebo* or "sham-control*" or ((single or double or triple or assessor) adj1 (blind* or masked)) or nonrandom* or "non-random*" or "quasi-experiment*" or "parallel group*" or "factorial trial" or "pretest posttest" or (phase adj5 (study or trial)) or (case* adj6 (matched or control*)) or (match* adj6 (pair or pairs or cohort* or control* or group* or healthy or age or sex or gender or patient* or subject* or participant*)) or (propensity adj6 (scor* or match*))).ti,ab,kf. or (confounding adj6 adjust*).ti,ab. or (versus or vs or compar*).ti. or ((exp cohort studies/ or epidemiologic studies/ or multicenter study/ or observational study/ or seroepidemiologic studies/ or (cohort* or 'follow up' or followup or longitudinal* or prospective* or retrospective* or observational* or multicent* or 'multi-cent*' or consecutive*).ti,ab,kf.) and ((group or groups or subgroup* or versus or vs or compar*).ti,ab,kf. or ('odds ratio*' or 'relative odds' or 'risk ratio*' or 'relative risk*' or aor or arr or rrr).ab. or (("OR" or "RR") adj6 CI).ab.)) |
5889055 |
|
9 |
4 and 5 |
4 |
|
10 |
(4 and 6) not 9 |
8 |
|
11 |
(4 and (7 or 8)) not (9 or 10) |
15 |
|
12 |
9 or 10 or 11 |
27 |