Radiotherapy

Publicatiedatum: 05-06-2026

Beoordeeld op geldigheid: 05-06-2026

Uitgangsvraag

Key question
Which radiotherapy technique, including the choice between fractionated and single-fraction radiotherapy, is recommended for patients with spinal metastases with and without spinal cord or cauda equina compression?

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Aanbeveling

Recommendations

Treat patients with pain but without spinal instability and without spinal cord or cauda equina compression with a single fraction of 8 Gy radiotherapy.

Consider stereotactic body radiotherapy (SBRT) or a more (ablative) fractionated radiotherapy regimen in patients for whom durable local tumor control is an important treatment objective.

Treat patients with a solitary metastasis and/or oligometastases (see definition in Table 4 in Considerations) with a radical dose. The potential benefit of this treatment should be discussed in the organ-specific multidisciplinary team meeting.

In patients with neurological deficits due to MESCC who are not eligible for, or decline, surgical treatment, administer a single fraction of 8 Gy radiotherapy.

Consider longer course radiotherapy (e.g., 16 Gy in 2 fractions, 20-25 Gy in 5 fractions, or 30 Gy in 10 fractions) for patients in good general condition (KPS > 60) with a life expectancy of ≥ 1 year, in order to improve the duration of response.
Do not offer radiotherapy to patients with complete paraplegia lasting longer than 2 weeks whose pain is adequately controlled.

Administer a second course of radiotherapy for recurrent or refractory pain, or neurological deficits following an initial or insufficient response to the first radiation treatment (not earlier than 4 weeks), due to the realistic chance of response, with dose and timing dependent on the initial radiation schedule, the dose to critical organs, and the time interval.

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Overwegingen

Considerations

Balance between desirable and undesirable effects

Radiotherapy remains a cornerstone in the management of metastatic bone disease. The optimal local management of patients with spinal metastases remains an important topic, particularly in those patients with a longer life expectancy. In these cases, treatment goals go beyond pain relief and include local tumor control, prevention of neurological complications and pathological fractures, and the preservation or improvement of mobility and quality of life.

Pain, local tumor control, and toxicity

An updated review of randomized trials continues to show equivalent outcomes in pain control and toxicity after a single dose of 8 Gy compared to multiple fraction conventional radiotherapy (cRT) in patients with uncomplicated bone metastases (Rich, 2018). Although patients with more favorable survival show better response rates, even in this patient group, no difference in pain response between single and multiple fraction radiotherapy was demonstrated (van der Linden, 2006). Evidence from a randomized phase III trial and large retrospective (real world) cohort indicates that, in cases of recurrent symptoms after an initial response or insufficient pain relief following the first course of radiotherapy, re-irradiation can be administered with a pain response rate of approximate 50–70% (Chow, 2014). Studies in this review included patients with spine but also non-spine bone metastases, of which the latter technically lie outside the scope of this guideline. However, there is no indication that the location of metastatic bone disease influences the outcomes assessed in cases of uncomplicated bone or spinal metastases (van der Linden, 2005; Howell, 2013).

It has been hypothesized that stereotactic radiotherapy (SBRT) might improve pain response compared to conventional radiotherapy techniques. To date, four randomized trials (Sprave, 2018; Sahgal, 2021; Ryu, 2023; Guckenberger, 2024) evaluated pain relief after cRT and SBRT in patients with spinal metastases. In these four trials, the median BED₁₀ was 50 Gy (range, 42-82 Gy) for the SBRT group and 28 Gy (range, 14-39 Gy) for the cRT group. The RTOG 0631 (Ryu, 2023) and the SC.24 (Sahgal, 2021) studies are the largest trials including 339 and 229 patients respectively.

The RTOG 0631 trial compared SBRT (16 or 18 Gy in 1 fraction) with cRT (8 Gy in 1 fraction) in patients with one to three spinal metastases. The study found no superiority of SBRT in pain relief at 3 months, which was the primary end point, showing a pain response of 41% for SBRT versus 61% for cRT. The SC.24 trial compared complete pain response in patients with painful, MRI-confirmed spinal metastases following delivery of cRT at a dose of 20 Gy in five fractions or SBRT at a dose of 24 Gy in two fractions. At 3 months, the proportion of patients with complete pain response was significantly higher with SBRT (35% vs. 14%). Importantly, although the SC.24 trial did report the proportion of patients who had a partial response for pain after cRT (29 (25%) of 115 patients) and SBRT (20 (18%) of 114) at 3 months, they did not statistically compare the two groups.

Gal and colleagues, pooling the results of the four spinal metastases trials (Sprave, 2018; Sahgal, 2021; Ryu 2023; Guckenberger, 2024) found that no difference was found at 1, 3 and 6 months after cRT and SBRT in overall response rate, but within the group of patients having a response, the complete pain response was better 3 months after SBRT (Gal, 2024). Bindels and colleagues pooled the results of eight randomized trials comparing cRT with SRT in patients with spinal and non-spine bone metastases (Bindels, 2024). The complete pain response was reported in 6 RCTs, and in agreement with Gal and colleagues, they also found that it was significantly higher at 1, 3 and 6 months after SBRT. Overall pain response rates did not differ between cRT and SBRT at these time points. In both meta-analyses, complete response rates from the RTOG 0631 trial could not be included. Wong and colleagues were able to also include the complete response data of the RTOG 0631 trial and found that SBRT does not provide better overall or complete pain response compared to cRT in patients with spinal metastases (Wong, 2023; Wong, 2025). The RTOG 0631 trial warrants consideration in light of several observations. This trial was developed prior to acknowledging the degree of mechanical instability in the spinal segment as a potential confounder of pain outcomes, in contrast to, for example, the SC.24 trial in which patients were eligible only with a SINS of 12 or less. Furthermore, more patients in the cRT arm had better performance status (i.e., a Zubrod score of 0 or 1), which may have influenced the results, as worse performance status is a known predictor of reduced pain response to radiotherapy (Westhoff, 2015; van der Velden, 2017). As compared with the other trials, RTOG 0631 used a nonstandard definition of pain response of at least 3 points of pain reduction instead of the 2 points reduction as agreed on in the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (Chow, 2012). Also, the RTOG 0631 trial included patients with a higher baseline pain score compared to the other RCTs, which may have made it more difficult for the SBRT arm to demonstrate relative benefit to the cRT arm. Finally, the dosing regimen of 16 Gy in one fraction was used in 55% of the patients in the SBRT arm and is regarded as a lower BED regimen compared with doses used in the other trials. It is unclear to what extent these factors contributed to the negative results. RTOG 0631 is the largest trial evaluating the role of SBRT for spinal bone metastases. As such, until further data on SBRT for painful bone metastases become available, its findings carry substantial weight in meta-analyses inclusive of these data toward a nonsignificant impact of SBRT over cRT approaches.

Wong and colleagues also performed a network meta-analysis to compare the relative efficacy of different SBRT regimens in achieving complete pain response at 3 months (Wong, 2025). Among the schedules evaluated, the 24 Gy in two fractions regimen from the SC.24 trial (Sahgal, 2021) was the only one to demonstrate a significantly superior complete pain response compared with cRT. This regimen also showed a statistically significant benefit over the single-fraction 16 Gy and 18 Gy regimens used in the RTOG 0631 trial (Ryu, 2023), but no significant difference compared to the single-fraction 24 Gy schedule studied by Sprave and colleagues (Sprave, 2018) or the multi-fraction regimens of 48.5 Gy in 10 fractions and 40 Gy in 5 fractions reported by Guckenberger and colleagues (Guckenberger, 2024). Interestingly, despite the higher BED₁₀ doses in the regimens by Guckenberger and colleagues (72 Gy₁₀) and Sprave and colleagues (81.6 Gy₁₀) compared with Sahgal and colleagues (52.8 Gy₁₀), these higher doses did not translate into higher complete pain responses in their network meta-analysis. These findings underscore the complexity of dose–response relationships in pain control for spinal metastases. Probably, fractionation does matter. Several possible radiobiological explanations for fractionation exist, including overcoming hypoxia, allowing damage repair by normal tissue cells, and redistribution of cycling cells (Redmond, 2015). It is possible that Sahgal and colleagues chose the appropriate SBRT dose regimen with the optimal number of fractions. Another explanation for the consistently superior complete pain response of SBRT in the SC.24 trial could be the inclusion of a higher proportion of patients with radioresistant tumors (e.g., renal cell cancer metastases). SBRT delivered in high doses per fraction may be particularly more effective in the treatment of metastases from radioresistant tumors (Wilson, 2003; De Meerleer, 2014). In the SC.24 trial, more than a quarter of the included patients had metastases from a radioresistant tumor, while the proportion of patients with radioresistant tumors in the other trials was less than 10%. Patients with radioresistant tumors may comprise a subgroup for whom SBRT is more effective than cRT in relieving pain caused by spinal metastases. As a decrease in pain score of 2 points is already considered as clinically relevant to patients with painful lesions (Westhoff, 2015), a combined endpoint of complete and partial responses for pain would be more clinically relevant than a complete response for pain alone. In the pragmatic randomized VERTICAL trial, which enrolled patients with bone metastases (excluding oligometastatic disease) and followed the Trials within Cohorts design, one in four patients preferred cRT to SBRT, while one in five who began SBRT could not complete the regimen (Pielkenrood, 2020). The review of Bindels and colleagues showed that response rates after SBRT were approximately 10 percentage points higher than after cRT at all time points (Bindels, 2024).

Another important treatment goal for patients with spinal metastases, especially for those with expected prolonged survival, is local tumor control, given the close proximity of the spinal cord or cauda, to prevent development of neurological symptoms due to cord or cauda compression. Two randomized trials assessed local control after treatment (Nguyen, 2019; Saghal, 2021). In a sub-cohort of the SC.24 trial (Sahgal, 2021) consisting of 137 of the study patients, long-term MRI-based local tumor control was reported (Zeng, 2022). In the 2-year post-trial follow-up, local control rates were significantly higher in the SBRT arm compared to the cRT arm with local failure of 15% vs. 36%, respectively (Zeng, 2022). The re-irradiation rates were also significantly lower (2.2% vs 16% at 1 year) and the median time to re-irradiation was 22 months in the SBRT group vs. 10 months in the cRT group. There was a trend toward increased local failure rates among radioresistant spine metastases in the cRT group compared with the SBRT group; the limited sample of radioresistant metastases may have led to a non-significant difference. In the trial of Nguyen and colleagues, predominantly non-spine bone metastases were treated, and local tumor control at the irradiated sites was non-standardized assessed with X-ray, CT, PET/CT, MRI, or bone scan. Local progression-free survival rates were significantly higher in the SBRT group than cRT group at 1 and 2 years. After SBRT, local control rates have been reported around 80-95% and a higher prescription (total) dose is associated with higher local control (Soltys, 2021; Guckenberger, 2024). Again, high doses per fraction may be particularly more effective in achieving local control of metastases from radioresistant tumors.

In general, radiotherapy for spinal metastases is associated with low rates of acute toxicity, both with conventional and stereotactic techniques. One study compared acute toxicity between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT), suggesting a slightly lower incidence of acute toxicity with IMRT (IRON trial, Sprave 2018-1). A key disadvantage of SBRT compared to cRT is the increased risk of vertebral compression fracture (VCF). VCF occurs in approximately 15% of patients, with half representing de novo fractures and the other half progression of pre-existing fractures; 65% of these fractures occur within the first four months following treatment, most often without the need for treatment (Saghal, 2013; Van den Brande, 2024). Several predictors have been identified including higher dose per fraction with the greatest risk observed for ≥24 Gy per fraction, VCF already at baseline, lytic tumor morphology, and spinal deformity (Saghal, 2013). Additionally, although rare, there is a small risk of radiation-induced myelopathy and plexopathy.

No trials specifically reported the duration of response, although some provided data on pain response at six months and re-irradiation rates as indirect indicators of response duration in the absence of difficult-to-collect longitudinal data.

Based on the considerations outlined above, the committee concluded that SBRT cannot be recommended over cRT as the standard-of-care treatment for pain relief in all patients with spinal metastases. Evidence suggests that the 24 Gy in two fractions SBRT regimen may provide superior complete pain response and could be considered when achieving complete pain relief is a primary treatment goal. For patients with painful spinal metastases in whom durable local tumor control is desired, who have a prolonged life expectancy or oligometastatic disease, and in whom SBRT is technically feasible - such as those who are not overtly unstable, have no or minimal epidural involvement (Bilsky 0–1c, Bilsky, 2010), and present with up to three contiguous vertebral segments in the radiation field - the committee considers SBRT to be a beneficial treatment option.

Metastatic spinal cord compression

Although there is no evidence on the timing of radiotherapy for patients with MSCC (see also module Treatment phase - timelines), the committee agreed that MSCC is an oncologic emergency and rapid access to radiotherapy is warranted in patients not undergoing surgery to maintain motor function or prevent neurological impairment. Various radiotherapy regimes have been used for the treatment of MSCC ranging from 2 Gy per day schedules delivering around 40 Gy to more hypofractionated schedules of 30 Gy in 10 fractions or 20 Gy in 5 fractions to single doses of 8–10 Gy. Several case series have been published with conflicting results, see also the literature review from the previous version of the guideline.

There are now four randomized trials (Maranzano, 2009; Abu-Hegazy, 2011; Lee, 2018; Hoskin, 2019;) providing high level evidence supporting the efficacy of single-fraction radiotherapy in MSCC. The earliest of these trials included 327 patients with a prognosis of less than 6 months. Of the 303 evaluable patients, 150 received 8 Gy in a single fraction and 153 received 16 Gy in two fractions. Radiotherapy was delivered within 24–48 hours of radiological diagnosis, covering two vertebrae above and below the level of compression, with dose prescribed to the cord depth. Median response duration was 4.5 months in the single-fraction group and 5 months in the multi-fraction group, while median overall survival was 4 months in both arms. No differences were observed in survival or ambulatory outcomes, and a non-significant difference was found between in field recurrences (2.5% after 16 Gy vs. 6% after 8 Gy) (Maranzano, 2009).

A second phase III randomized trial compared three fractionation schedules - 8 Gy in a single fraction, 30 Gy in 10 fractions, and 40 Gy in 20 fractions - in 285 patients with MSCC. No significant differences were found in functional outcomes or toxicity measured at several time points after radiotherapy. However, at 2 years, among the 162 patients with in-field recurrence data, single-fraction treatment was associated with a higher recurrence rate compared with multi-fraction regimens (22.2% vs. 16.1% (30 Gy in 10 fractions) vs. 13.5% (40 Gy in 20 fractions)) (Abu-Hegazy, 2011).

The ICORG 05–03 phase III, randomized, multicenter non-inferiority trial compared 10 Gy in a single fraction with 20 Gy in 5 fractions, also including one vertebral margin above and below the compression site (Lee, 2018; Thirion, 2020). A total of only 112 patients were enrolled, of whom 73 were analyzed. The study concluded that a single 10 Gy fraction was non-inferior to 20 Gy in 5 fractions, with lower toxicity and no difference in median overall survival (6.6 vs. 6 months).

The SCORAD III phase III trial randomized 686 patients with MSCC and an expected prognosis of more than 8 weeks to receive either a single dose of 8 Gy or 20 Gy in 5 fractions (Hoskin, 2019; Hoskin, 2024). Treatment began within 48 hours of decision-making, using conventional megavoltage techniques, and encompassed one vertebra above and below the compression site. Except at week 8 (the primary endpoint), all time points met criteria for non-inferiority in ambulatory status. Median survival was similar between arms (12 vs. 13 weeks). The SCORAD trial showed that most patients were ambulatory with(out) walking aid and maintained the ability to walk (62%); only a minority of patients who could not walk improved in ambulatory status (7-10%).

A systematic review and meta-analysis compared single-fraction radiotherapy with short-course multi-fraction radiotherapy (defined as regimens delivered within one week) for MSCC (Donovan, 2019), including the studies of described above except for Abu-Hegazy (Abu-Hegazy, 2011). Overall, no significant differences were found in motor response or overall survival between single-fraction and multi-fraction approaches.

In one of Rades’ non-randomized studies, the median response duration was 5 months following single-fraction radiotherapy and 7.5 months with longer fractionation schedules (Rades, 2009). Recurrent spinal cord compression occurred in 18% (20/114) of patients in the single-fraction or short-course group versus 9% (10/117) in the long-course group. Local control, defined as the absence of recurrent compression within the irradiated field, was significantly better with long-course treatment (77%) compared with short-course treatment (61%). In another Rades non-randomized study, recurrent neurological deficits occurred in 10% (12/118) of patients treated with 30 Gy in 10 fractions, 11% (10/90) with 37.5 Gy in 15 fractions, 16% (12/76) with 40 Gy in 20 fractions, 32% (33/104) with 20 Gy in 5 fractions, and 37% (34/91) with 8 Gy single fraction (p < 0.01) (Rades, 2005). In a multicenter phase 2 trial (PRE-MODE trial), Rades and colleagues evaluated 40 patients with metastatic spinal cord compression receiving 25 Gy in 5 fractions (which is similar to 30 Gy in 10 fractions). Of these patients, 16 patients (42%) were not ambulatory before radiation therapy. In this cohort, the 6-month local progression free survival was 95% with a 6-month survival of 45%, and improvement of motor function occurred in 24 patients (60%). It was concluded that 25 Gy in 5 fractions is a well-tolerated and effective treatment. In comparison with a historical cohort, it appeared superior to shorter treatment schedules (Rades, 2019).

In the context of metastatic spinal cord compression (MSCC), the role of SBRT remains uncertain with scare published data to date. No randomized trials have directly addressed this question. A recent meta-analysis (Van den Brande, 2024) pooled results on local tumor control after cRT and SBRT - with or without separation surgery - in ambulatory MSCC patients. Most included studies were retrospective or prospective cohorts; only one randomized controlled trial compared surgery plus cRT with cRT alone (Patchell, 2005). SBRT showed a statistically significant advantage in 1-year local control (85%, 95% CI 82–87%) versus cRT (76%, 95% CI 74–78%). In the cRT group, five of nine studies included highly radiosensitive tumors (e.g., multiple myeloma and lymphoma), which likely increased the local control rate. Excluding these, cRT local control dropped to 66% (95% CI 62–71%).

The optimal treatment strategies for MSCC require a multidisciplinary approach, which continues to evolve. This strategy is discussed in module Combination of radiotherapy and surgery.

Definition of oligometastases
There is no uniform definition of oligometastases. Table 4 presents several consensuses that are commonly used in Dutch practice, depending on the tumor type.

Table 4. Overview of commonly used definitions of oligometastases

Tumor Type	Definition
Prostate cancer	Up to 5 lesions detected on PSMA PET scan.
Esophageal carcinoma	A limited number of metastases (usually 1–3) representing a transitional phase between local disease and widespread metastatic spread.
Lung cancer	No consensus definition. Most studies define oligometastases as a maximum of 5 lesions in up to 3 organs.
Renal cancer	1–3 metastases in a maximum of 2 organ systems.
Breast cancer	Oligometastatic breast cancer is defined as 1–5 metastatic lesions, all eligible for safe local or locoregional treatment (Lievens, 2020). In clinical practice, the default is 1–2 metastases, extendable to 3–5 under specific conditions depending on the primary tumor, systemic therapy, patient condition, and preferences (Steenbruggen, 2021).

Quality of evidence
For evidence from the NICE guideline (indicated in grey in Table 2 in the Appendix: Summary of Findings per outcome), please refer directly to the NICE guideline for the quality assessments. The quality of evidence from the update search is reported below.

For the outcome pain relief one month after treatment, the overall quality of evidence is low. This means we are uncertain about the estimated effect of the observed pain relief. The rating was downgraded due to methodological limitations (lack of blinding) and because the optimal sample size was not reached. Publication bias was not assessed.

For the outcome pain relief three months after treatment, it is unclear whether SBRT or cEBRT is more favorable. The overall quality of evidence is very low. The rating was downgraded due to methodological limitations (lack of blinding), failure to reach the optimal sample size, and inconsistency in the results. Publication bias was not assessed.

In the update search for this module, no results were found regarding neurological outcomes.

With regard to HR-QoL, no difference was demonstrated between SBRT and cEBRT at different time points after treatment (1 month, 8 weeks, 3 months, and 6 months). The overall quality of evidence is moderate to low. The rating was downgraded due to methodological limitations (lack of blinding) and failure to reach the optimal sample size. Publication bias was not assessed.

Values and preferences of patients (and possibly their relatives/caregivers)

One of the main advantages of a single 8 Gy fraction is the speed of treatment. Apart from a planning CT scan for radiotherapy preparation, no additional procedures are required. As a result, treatment can typically be started within at the same day or a few days after the initial consultation. For patients, this means a quick procedure that takes only a few minutes, and they usually need to visit the hospital no more than twice: once for the consultation and for the planning CT and treatment.

In contrast, treatment with SBRT often requires additional preparation, such as a planning MRI in combination with the planning CT. For spinal metastases, often a vacuum mattress is used, which must be custom-made. This often results in an additional delay of 1–2 weeks before treatment can begin. The actual treatment time per session is also longer: whereas a single 8 Gy fraction takes about 10 minutes, an SBRT session typically lasts around 30 to 45 minutes.

However, when there is a potential benefit for preserving or improving mobility and quality of life, most patients are willing to endure the more complex treatment, along with its preparations and longer waiting time.

From the pragmatic randomized VERTICAL trial, including patients with bone metastases excluding oligometastatic disease, which followed the Trials within Cohorts design, we learn that 1 in 4 patients preferred to undergo cRT over SBRT, and 1 in 5 patients starting SBRT was unable to complete this treatment (Pielkenrood, 2020).

Cost aspects

Local treatment by means of radiotherapy incurs costs, with stereotactic radiotherapy being more expensive than conventional treatment. 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.

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 use conventional radiotherapy or SBRT is a medical one, 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
SBRT is a treatment that is available at all radiotherapy departments in the Netherlands. Given the recommendation of the working group to generally treat painful bone metastases with conventional radiotherapy (1x8 Gy), this will not pose any issues in terms of feasibility or implementation.

If radiotherapy departments begin using SBRT more frequently in an effort to achieve complete response or local tumor control, this will result in an increased burden.

It is important to mention that treatment with conventional radiotherapy places less strain on machine capacity compared to SBRT, due to the longer treatment duration and greater complexity of the latter technique.

Onderbouwing

Background

Radiotherapy is a widely used treatment modality for patients with spinal metastases. Due to the close proximity of the spinal cord and nerve roots to the vertebrae, radiotherapy plays an important role not only in terms of pain relief, but also in preventing or reducing neurological symptoms (Oldenburger 2022). For uncomplicated painful spinal metastases, a single fraction of 8 Gy is the gold standard (Van der Velden, 2022; Chow, 2012), and from a patient's perspective, a single, straightforward treatment is generally preferred over a prolonged schedule. The introduction of stereotactic radiotherapy has enabled the delivery of higher doses still within a limited number of fractions. In 2015, the guideline committee concluded that there was insufficient evidence to support the added value of advanced radiotherapy techniques and recommended awaiting the results of ongoing randomized trials. Since then, several randomized trials comparing stereotactic with conventional radiotherapy were published, allowing a review of these studies in the current revision of this guideline. This module first discusses the literature search according to the GRADE system. Pain and neurological symptoms are briefly discussed as separate indications, as the role of radiotherapy and considerations differs between the 2 indications.

For this module, the committee has made use of the search and recommendations of the recent NICE guideline (2023), supplemented by our updated literature search (2021-2025). In addition, several outcome measures not included in the NICE guideline are discussed. Regarding bisphosphonates, the recently published Dutch guideline on bone metastases notes that little is still known about the potential synergistic effect between these agents and radiotherapy, and the committee refers to this guideline with regard to this topic (Guideline Bonemetastases, chapter medication). Furthermore, wherever the term metastatic spinal cord compression appears, it can also be understood as compression of the cauda equina compression.

Summary of Findings per outcome

Outcome	Study	Measurement	Intervention	Control group	Difference (95%CI)	Certainty of the Evidence (Quality of evidence)	Conclusions
pain relief	Guckenberger 2024	Proportion of pain score reduction ≥2 on VAS: 1 month	SBRT 48.5 Gy (10 fraction) or 40 Gy (5 fraction): 23/36 (63.9%)	cEBRT 30 Gy (10 fraction) or 20 Gy (5 fraction): 17/31 (54.8%)	OR 1.17 (not reported) p=0.45	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in little to no difference in pain relief at 1 month after treatment in patients with spinal metastases.
		Proportion of complete pain response: 1 month	SBRT 48.5 Gy (10 fraction) or 40 Gy (5 fraction): 9/36 (25.0%)	cEBRT 30 Gy (10 fraction) or 20 Gy (5 fraction): 6/31 (19.4%)	OR 1.29 (not reported) p=0.58	Low^1,2
		Proportion of progressive pain: 1 month	SBRT 48.5 Gy (10 fraction) or 40 Gy (5 fraction): 8/36 (22.2%)	cEBRT 30 Gy (10 fraction) or 20 Gy (5 fraction): 8/31 (25.8%)	OR 0.86 (not reported) p=0.74	Low^1,2
		Proportion of pain score reduction ≥2 on VAS: 6 month	25/36	13/31	OR 1.66 (not reported) p=0.02	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in more frequent pain score reduction ≥2 on VAS at 6 month after treatment in patients with spinal metastases.
		Proportion of complete pain response: 6 month	8/36	9/31	OR 0.77 (not reported) p=0.53	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in in little to no difference in complete pain response at 6 month after treatment in patients with spinal metastases.
		Proportion of progressive pain: 6 month	8/36	13/31	OR 0.53 (not reported) p=0.09	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in less frequent progressive pain at 6 month after treatment in patients with spinal metastases.
		Proportion of pain score reduction ≥2 on VAS: 3 month	19/36 (52.8%)	13/31 (41.9%)	OR 1.26 (not reported) p=0.38	Very low ^1,2,3	The evidence is very uncertain whether SBRT provides greater pain relief at 3 month after treatment compared with cEBRT in patients with spinal metastases.
		Proportion of complete pain response: 3 month	7/36 (19.4%)	5/31 (16.1%)	OR 1.21 (not reported) p=0.73	Very low ^1,2,3
		Proportion of progressive pain: 3 month	11/36 (30.6%)	11/31 (35.5%)	OR 0.86 (not reported) p=0.67	Very low ^1,2,3
	Ryu 2023 (RTOG 0631)	Proportion of pain responses at 3 months	SRS 16 or 18 Gy (single dose): 41.3% (57/138)	cEBRT 8 Gy (single dose): 60.5% (46/76)	OR 0.68 (not reported) 1-sided p=0.99; Estimated between-group difference: -19% (-32.9% to -5.5%)	Very low ^1,2,3
	Ryu 2023 (RTOG 0631)	Treatment effect at 3 months (estimated using mixed effect modling)			OR 2.02 (0.97-4.19) p=0.06 (in favor of cEBRT)	Very low ^1,2,3
	Howell 2013 (RTOG 97-14), Majumder 2012, Roos 2005	Complete or partial pain response (follow-up 1 to 3 months)	Single fraction 8 Gy: 152/245 (62%)	Multiple fraction (10x3 GY): 157/244 (64.3%)	RR 0.97 (0.85 to 1.11) 19 fewer per 1000 (from 97 fewer to 71 more)	Very low⁵	There was very low to low quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of pain reduction, spinal stability and overall survival. There was very low quality evidence of an important benefit with single fraction radiotherapy which had fewer treatment related adverse events than multiple fractions among people with painful spinal bone metastases (but no evidence of spinal cord compression.
	Maranzano 2005	Complete or partial pain response after treatment	16 Gy in 2 fractions: 80/142 (56.3%)	Split course RT: 79/134 (59%)	RR 0.96 (0.78 to 1.17) 24 fewer per 1000 (from 130 fewer to 100 more)	Modereate⁵	There was moderate to high quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of neurological and functional status, quality of life, pain, overall survival and treatment toxicity among people with metastatic spinal cord compression.
	Maranzano 2009	Complete or partial pain response	single fraction 8 Gy: 80/153 (52.3%)	16 Gy in 2 fractions: 80/150 (53.3%)	RR 0.98 (0.79 to 1.21) 11 fewer per 1000 (from 112 fewer to 112 more)	Modereate⁵
	Hoskin 2019 (SCORAD-III trial)	Pain score (standardised mean difference between groups at 8 week follow-up)	single fraction RT: n=345	Multiple (or short) fraction RT: n=341	SMD 0.12 higher (1-sided 97.5% CI ∞ lower to 0.38 higher)	Modereate⁵
	Sprave 2018a	Complete or partial pain response (follow-up 3 months)	Image guided intensity modulated RT: 14/20 (70%)	conventional RT: 9/19 (47.4%)	RR 1.48 (0.85 to 2.57) 227 more per 1000 (from 71 fewer to 744 more)	Very low⁵	There was no evidence of an importance difference between IMRT and 3D-CRT in terms of quality of life, pain response, treatment related morbidity or overall survival in one small trial among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Sahgal 2021	complete or partial pain response (1 months follow-up)^$	SABR: 64/114 (56.1%)	Conventional RT: 53/115 (46.1%)	RR 1.21 (0.94 to 1.57)	Very low⁵	There was an important benefit with SABR when compared to conventional RT (EBRT or 3D-CRT) in reducing pain at 3 and 6 months follow-up among people with painful spinal bone metastases (but no evidence of spinal cord compression). There was no evidence of important differences in quality of life, treatment related morbidity or overall survival. This evidence was all low quality.$
	Sahgal 2021	complete or partial pain response (3 months follow-up)^$	SABR: 60/114 (52.6%)	Conventional RT: 45/115 (39.1%)	RR 1.35 (1.01 to 1.79)	Very low⁵
	Sahgal 2021 (SC.24 trial), Sprave 2018d	complete or partial pain response (6 months follow-up)	SABR: 61/141 (43.3%)	Conventional RT: 43/143 (30.1%)	RR 1.44 (1.05 to 1.97) 132 more per 1000 (from 15 more to 292 more)	Very low⁵
	Rades 2016 (SCORE-2 trial)	Complete or partial pain response (1 month follow-up)	20 Gy in 5 fractions: 36/101 (35.6%)	30 Gy in 10 fractions: 40/102 (39.2%)	RR 0.91 (0.64 to 1.3) 35 fewer per 1000 (from 141 fewer to 118 more)	Low⁵	There was low to high quality evidence of no important difference between short course radiotherapy and split or long course radiotherapy in terms of neurological and functional status, pain response and treatment related morbidity among people with metastatic spinal cord compression.
Neurological status	Hoskin 2019 (SCORAD=III), Lee 2018 (ICORG 05-03 trial) Maranzano 2009	Ability to walk after treatment	Single fraction 8 Gy: 238/355 (67%)	Multiple (or short) fraction RT: 256/363 (70.5%)	RR 0.95 (0.86 to 1.05) 35 fewer per 1000 (from 99 fewer to 35 more)	High⁵	There was moderate to high quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of neurological and functional status, quality of life, pain, overall survival and treatment toxicity among people with painful spinal bone metastases (but no evidence of spinal cord compression.
	Hoskin 2019	Normal bladder function	Single fraction RT: 184/316 (58.2%)	Multiple (or short) fraction RT: 211/322 (65.5%)	RR 0.89 (0.79 to 1.00) 72 fewer per 1000 (from 138 fewer to 0 more)	Modereate⁵
	Hoskin 2019, Maranzano 2009	Normal bowel function after treatment	Single fraction RT: 242/468 (51.7%)	Multiple (or short) fraction RT: 249/472 (52.8%)	RR 0.97 (0.87 to 1.08) 16 fewer per 1000 (from 69 fewer to 42 more)	High⁵
	Maranzano 2005	Ability to walk after treatment	Short course RT: 97/142 (68.3%)	Split course RT: 95/134 (70.9%)	RR 0.96 (0.82 to 1.13) 28 fewer per 1000 (from 128 fewer to 92 more)	High⁵	There was low to high quality evidence of no important difference between short course radiotherapy and split or long course radiotherapy in terms of neurological and functional status, pain response and treatment related morbidity among people with metastatic spinal cord compression.
	Maranzano 2005	Normal sphincter control after treatment	Short course RT: 128/142 (90.1%)	Split course RT: 119/134 (88.8%)	RR 1.02 (0.94 to 1.1) 18 more per 1000 (from 53 fewer to 89 more)	High⁵
	Rades 2016	Ambulatory status (1 month follow-up)	Short course RT: 56/78 (71.8%)	Long course RT: 57/77 (74%)	RR 0.97 (0.80 to 1.18) 22 fewer per 1000 (from 148 fewer to 133 more)	High⁵
	Rades 2016	Motor deficits improved or stable (1 month follow-up)	Short course RT: 68/78 (87.2%)	Long course RT: 69/77 (89.6%)	RR 0.97 (0.87 to 1.09) 27 fewer per 1000 (from 116 fewer to 81 more)	High⁵
HR-QoL	Guckenberger 2024	Mean ± sd of EQ‐VAS: 1 month	68.8 ± 18.4	59.3 ± 25.1	p=0.15	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in beter EQ-VAS score at 1 month after treatment in patients with spinal metastases.
		Mean ± sd of EQ‐VAS: 3 month	70.3 ± 15.8	70.1 ± 18.5	p=0.98	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in little to no difference in HR-QoL at 3 months, and 6 months after treatment in patients with spinal metastases.
		Mean ± sd of EQ‐VAS: 6 month	64.3 ± 14.7	63.9 ± 22.7	p=0.94	Low^1,2
	Ryu 2023	Treatment effect at 3 months on FACT-G total score (estimated using mixed effect modling)	Not applicable	Not applicable	Complete cases: 1.29 ± standard error 1.75; p=0.46 Imputed data: 5.02 ± standard error 5.46; p=0.36	Low^1,2
	Hoskin 2024§	Mean ± sd in HRQoL at 8 weeks: Global Health Status	43.73 ± 23.36	42.73 ± 25.33	−1.76 (−9.66 to +6.13)* p=0.56	Moderate²	The use of SBRT likely results in little to no difference in HR QoL compared with cEBRT at 8 weeks after treatment in patients with metastatic spinal cord compression
		Mean ± sd in HRQoL at 8 weeks: Physical functioning	35.35 ± 31.30	37.09 ± 29.92	−2.99 (−11.86 to +5.88)* p=0.38
		Mean ± sd in HRQoL at 8 weeks: QLU-C10D	0.47 ± 0.24	0.45 ± 0.24	-0.01 (−0.09 to +0.07)* p=0.67
	Hoskin 2019	EORTC QLQ-C30 Global health (SMD at 2 months, adjusted for baseline value)	Single fraction RT: n=345	Multiple (or short) fraction RT: n=341	SMD 0.13 lower (1-sided 97.5% CI 0.38 lower to ∞ higher)	Moderate⁵	There was moderate to high quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of neurological and functional status, quality of life, pain, overall survival and treatment toxicity among people with metastatic spinal cord compression.
		EORTC QLQ-C30 Physical functioning (SMD at 2 months, adjusted for baseline value)			SMD 0.12 lower (1-sided 97.5% CI 0.35 lower to ∞ higher)
		EORTC QLQ-C30 Emotional functioning (SMD at 2 months, adjusted for baseline value)			SMD 0.18 lower (1-sided 97.5% CI 0.41 lower to ∞ higher)
	Sprave 2018a	EORTC QLQ-BM 22 Functional interference (at 6 months follow-up)	Image guided intensity modulated RT: n=17	conventional RT: n=12	MD 0.3 higher (19.74 lower to 20.34 higher)	Very low⁵	There was no evidence of an importance difference between IMRT and 3D-CRT in terms of quality of life, pain response, treatment related morbidity or overall survival in one small trial among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Sprave 2018a	EORTC QLQ-BM 22 Psychosocial aspects (at 6 months follow-up)	Image guided intensity modulated RT: n=17	conventional RT: n=12	MD 13.6 lower (30.48 lower to 3.28 higher)	Very low⁵
	Sprave 2018d	EORTC QLQ-BM 22 Functional interference (at 6 months follow-up)	SBRT: n=19	Conventional RT: n=20	MD 3.4 higher (8.97 lower to 15.77 higher)	Very low⁵	There was no evidence of important differences in quality of life, treatment related morbidity or overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was all low quality.
	Sprave 2018d	EORTC QLQ-BM 22 Psychosocial aspects (at 6 months follow-up)	SBRT: n=19	Conventional RT: n=20	MD 1.7 lower (17.15 lower to 13.75 higher)	Very low⁵
	Sahgal 2021	EORTC QLQ-BM 22 Global quality of life, change from baseline to 6 months	SBRT: n=115	Conventional RT: n=114	MD 5.10 higher (2.67 lower to 12.87 higher)	Low⁵
Response duration	Ryu 2023	Duration of pain response at 12 months (defined as the date of first complete or partial response to the date of first progressive response)	Pain respons/total 6/140	Pain respons/total 2/80	SRS/cEBRT: HR 0.54 (0.11-2.68) p=0.44	Very low^1,4	The evidence is very uncertain about whether SBRT reduces the risk of pain progression within 12 months after an initial pain response, compared to cEBRT in patients with spinal metastases.
Treatment related morbidity	Howell 2013, Majumder 2012	Grade 2 to 4 adverse events	Single fraction RT: 6/155 (3.9%)	Multiple fraction RT: 17/144 (11.8%)	RR 0.35 (0.14 to 0.85) 77 fewer per 1000 (from 18 fewer to 102 fewer)	Very low⁵	There was very low to low quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of pain reduction, spinal stability and overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression). There was very low quality evidence of an important benefit with single fraction radiotherapy which had fewer treatment related adverse events than multiple fractions.
	Roos 2005	Moderate or severe flare effect	Single fraction RT: 12/137 (8.8%)	Multiple fraction RT: 4/135 (3%)	RR 2.96 (0.98 to 8.94) 58 more per 1000 (from 1 fewer to 235 more)	Low⁵
	Majumder 2012	Treatment discontinuation due to adverse events	Single fraction RT: 0/31 (0%)	Multiple fraction RT: 0/33 (0%)	0 fewer per 1000 (from 60 fewer to 60 more)	Low⁵
	Hoskin 2019, Maranzano 2009	Grade 3 or 4 adverse events	Single fraction RT: 71/498 (14.3%)	Multiple (or short) fraction RT: 72/491 (14.7%)	RR 0.97 (0.73 to 1.3) 4 fewer per 1000 (from 40 fewer to 44 more)	Low⁵
	Sprave 2018a	Grade 3 to 4 adverse events (follow-up 3 months)	Image guided intensity modulated RT: 1/30 (3.3%)	conventional RT: 4/30 (13.3%)	RR 0.25 (0.03 to 2.11) 100 fewer per 1000 (from 129 fewer to 148 more)	Very low⁵	There was no evidence of an importance difference between IMRT and 3D-CRT in terms of quality of life, pain response, treatment related morbidity or overall survival in one small trial among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Sahgal 2021	Grade 3 adverse event (6 months follow-up)	SBRT: 5/115 (4.3%)	Conventional RT: 5/114 (4.4%)	RR 0.99 (0.29 to 3.33) 0 fewer per 1000 (from 31 fewer to 102 more)	Very low⁵	There was no evidence of important differences in quality of life, treatment related morbidity or overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Maranzano 2005	Grade 3 or more adverse events	Short course RT: 3/142 (2.1%)	Split course RT: 5/134 (3.7%)	RR 0.57 (0.14 to 2.32) 16 fewer per 1000 (from 32 fewer to 49 more)	Low⁵	There was low to high quality evidence of no important difference between short course radiotherapy and split or long course radiotherapy in terms of neurological and functional status, pain response and treatment related morbidity among people with metastatic spinal cord compression.
	Rades 2016	Grade 3 or 4 acute toxicity	Short course RT: 0/101 (0%)	Long course RT: 0/102 (0%)	RD 0.00 0 fewer per 1000 (from 20 fewer to 20 more)	Moderate⁵
Overall survival	Guckenberger 2024	Proportion of patients survived at 12 months	0.62 (0.45-0.79)	0.60 (0.41-0.79)	HR 1.1 (0.52-2.31) p=0.79	Low ^2,3	The evidence suggests SBRT compared with cEBRT may result in little to no difference in overall survival at 12 months in patients with spinal metastases.
	Ryu 2023	Proportion of patients survived at 12 months	44.3%	53.1%	HR 0.91 (0.69-1.20) p=0.51	Low ^2,3
	Howell 2013, Roos 2005	Event is death from any cause; median follow-up 11 months	Single fraction RT: 242/261 (92.7%)	Multiple fraction RT: 224/246 (91.1%)	HR 1.08 (0.9 to 1.29) 16 more per 1000 (from 24 fewer to 45 more)	Very low⁵	There was very low to low quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of pain reduction, spinal stability and overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression).
	Hoskin 2019, Maranzano 2009	Event is death from any cause	Single fraction RT: 419/494 (84.8%)	Multiple (or short) fraction RT: 413/495 (83.4%)	HR 1.06 (0.88 to 1.28)	Moderate⁵	There was moderate to high quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of neurological and functional status, quality of life, pain, overall survival and treatment toxicity among people with metastatic spinal cord compression.
	Sprave 2018a	Event is death from any cause; median follow-up 6 months	Image guided intensity modulated RT: 14/30 (46.7%)	conventional RT: 7/30 (23.3%)	HR 2.02 (0.81 to 5)	Very low⁵	There was no evidence of an importance difference between IMRT and 3D-CRT in terms of quality of life, pain response, treatment related morbidity or overall survival in one small trial among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Sprave 2018d	Event is death from any cause	SBRT: 15/27 (55.6%)	Conventional RT: 15/28 (53.6%)	HR 1 (0.49 to 2.05)	Very low⁵	There was no evidence of important differences in quality of life, treatment related morbidity or overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Rades 2016	Event is death from any cause; median follow-up 6 months	Short course RT: 9/101 (8.9%)	Long course RT: 9/102 (8.8%)	HR 1.21 (0.48 to 3.06) 18 more per 1000 (from 45 fewer to 158 more)	Low⁵	There was low to high quality evidence of no important difference between short course radiotherapy and split or long course radiotherapy in terms of neurological and functional status, pain response and treatment related morbidity among people with metastatic spinal cord compression.
Local control	Guckenberger 2024	Proportion of patients with radiologic progression	1/32 (3.1%)	2/25 (8.0%)	OR 0.39 (not reported) p=0.42	Very low^1,4*	The evidence is very uncertain about whether SBRT result in a lower rate of radiologic progression compared with cEBRT in patients with spinal metastases.
	Ryu 2023	Proportion of patients with spinal cord signal change on MRI at 24 months	3.6% (1.6%-6.9%)	1.7%(0.3%-5.4%)	OR 2.12 (not reported) p=0.38	Very low^1,4*
	Ryu 2023	Proportion of patients with progression of known metastases	34.0%	42.3%	OR 0.80 (not reported) p=0.12	Low^1,2*	The evidence suggests SBRT compared with cEBRT may result in little to no difference in progression of known metastases in patients with spinal metastases.
	Sahgal 2021§	Radiation site-specific progression events up to the 6-month follow-up	28/114 (24.6%)	36/115 (31.3%)	OR 0.71 (0.40-1.28)	Very low^1,4	The evidence suggests SBRT may result in less radiation site-specific progression events at 6 months follow-up compared with cEBRT in patients with spinal metastases.
		Radiation site-specific progression-free survival (defined as the time from randomisation to local progression or death) rate at 6 months,	75% (95% CI 65%-82%)	69% (95% CI 60%-77%)	P=0.34	Low^1,2	The evidence suggests SBRT compared with cEBRT may result in little to no difference in radiation site-specific progression-free survival rate at 3 and 6 months follow-up in patients with spinal metastases.
		Radiation site-specific progression-free survival (defined as the time from randomisation to local progression or death) rate at 3 months	92% (95% CI 85%-96%)	86% (95% CI 78%-91%)	P=0.18	Low^1,2
	Rades 2016§	local progression-free survival (freedom from both deterioration of motor deficits during or directly after RT and in-field recurrence of MESCC) at 3 months	Short course RT: 52/67 (77.1%)	Long course RT: 49/58 (83.9%)	P=0.51	Low⁴	The evidence suggests short course RT compared with long course RT may result in little to no difference in radiation site-specific progression-free survival rate at 3 and 6 months follow-up in patients with spinal metastases.
	Rades 2016§	local progression-free survival (freedom from both deterioration of motor deficits during or directly after RT and in-field recurrence of MESCC) at 6 months	Short course RT: 39/52 (75.2%)	Long course RT: 34/42 (81.8%)	P=0.51	Low⁴
Spinal stability	Roos 2005	cord compression (median follow-up 11 months)	Single fraction RT: 9/137 (6.6%)	Multiple fraction RT: 8/135 (5.9%)	RR 1.11 (0.44 to 2.79) 7 more per 1000 (from 33 fewer to 106 more)	Very low⁵	There was very low to low quality evidence of no important difference between single fraction radiotherapy and multiple fractions in terms of pain reduction, spinal stability and overall survival. There was very low quality evidence of an important benefit with single fraction radiotherapy which had fewer treatment related adverse events than multiple fractions.
	Roos 2005, Steenland 1999	fractures (median follow-up 11 months)	Single fraction RT: 10/302 (3.3%)	Multiple fraction RT: 6/312 (1.9%)	RR 1.68 (0.62 to 4.53) 13 more per 1000 (from 7 fewer to 68 more)	Very low⁵
	Sprave 2018a	pathologic fractures (follow-up 3 months)	Image guided intensity modulated RT: 3/20 (15%)	conventional RT: 2/19 (10.5%)	RR 1.42 (0.27 to 7.61) 44 more per 1000 (from 77 fewer to 696 more)	Very low⁵	There was no evidence of an importance difference between IMRT and 3D-CRT in terms of quality of life, pain response, treatment related morbidity or overall survival in one small trial among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Sahgal 2021, Sprave 2018d	vertebral compression fracture of any grade (6 months follow-up)	SBRT: 23/132 (17.4%)	Conventional RT: 26/135 (19.3%)	RR 1.09 (0.33 to 3.66) 17 more per 1000 (from 129 fewer to 512 more)	Very low⁵	There was no evidence of important differences in quality of life, treatment related morbidity or overall survival among people with painful spinal bone metastases (but no evidence of spinal cord compression. This evidence was very low quality.
	Maranzano 2005	in field recurrence	Short course RT: 5/142 (3.5%)	Split course RT: 0/134 (0%)	POR 7.19 (1.23 to 42.06) 40 more per 1000 (from 0 more to 70 more)	Moderate⁵	There was low to high quality evidence of no important difference between short course radiotherapy and split or long course radiotherapy in terms of neurological and functional status, pain response and treatment related morbidity among people with metastatic spinal cord compression.
Skeletal related events	Guckenberger 2024	Proportion of patients with vertebral compression fracture	19.4%	13.3%	OR 1.46 (not reported) p=0.47	Low^1,2*	The evidence suggests SBRT compared with cEBRT may result in little to no difference in proportion of vertebral compression fractures in patients with spinal metastases.
Skeletal related events	Ryu 2023	Proportion of vertebral compression fractures at 24 months	19.5%	21.6%	OR 0.90 (not reported) p=0.59	Low^1,2*
Costs		Not reported				NO GRADE
_{Of note, results marked in gray are extracted from the NICE guideline. For details on the study characteristics, please refer to the NICE guideline.} _{Abbreviations: OR, odds ratio; HR, hazard ratio; SMD, standardized mean difference; POR, Peto odds ratio;} _{¹ Due to risk of Bias: serious. Due to lack of blinding.} _{² Due to imprecision: serious. Due to unreported confidence interval or overlap of the upper limit of the 95% confidence interval with the minimal clinically important difference.} _{³ Due to inconsistency: serious. Due to unexplained difference of results across studies.} _{⁴ Due to imprecision: very serious (downgraded for two levels). Due to few events and the CI includes appreciable benefit and harm, or confidence interval overlap with both the lower and the upper limit of the 95% confidence interval with the minimal clinically important difference.} _{^$ The results on pain relief at 1- and 3-month follow-up are not included in the NICE guideline. The conclusion has been slightly adjusted compared to the conclusion in the NICE guideline.} _{*The proportion of patients was analyzed at the time of analysis of the study, which was after a median follow-up of 10 (interquartile range 5-15 months).} _{^5. Certainty of evidence evaluated in NICE guideline.} _{^§ These two studies were included in the NICE guideline, although results about local control were extracted. Therefore only data on local control has been re-extracted, using the risk of bias assessment from the NICE guideline as a reference.} _{Publication bias is not evaluated.}

Summary of literature

Description of studies

In the NICE guideline, 19 randomized trials were included (NICE guideline, evidence M). A total of three studies were included in the literature analysis in addition to the studies included in the NICE guideline. Important study characteristics and results are summarized in table 3. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Table 3. Characteristics of included studies

Study

Participants

Comparison

Follow-up

Outcome measures and effect size

RoB/Comments

Guckenberger 2024

Patients had a histologically proven diagnosis of a solid tumor (excluding lymphoma, small cell lung cancer, multiple myeloma, and germ cell tumors), and a maximum two of distinct painful vertebral metastases.

Inclusion criteria: aged 18 years or older; and a Karnofsky performance status ≥60%, and a life expectancy >1 year according to the investigator's assessment.

Exclusion criteria:

Had spinal instability (a spinal instability neoplastic score >12), involvement of more than three (cervical spine) or four (thoracic, lumbar, sacral spine) contiguous vertebrae, more than two treatment sites, progressive neurologic symptoms/deficits, previous radiotherapy, or previous radionuclide therapy at the treated site or surgery of the affected vertebra. Radiosensitizing agents were not allowed during radiotherapy.

N at baseline

Intervention: n=33 (metastases n=36)

Control: n=30 (metastases n=31)

Age median (range)

Intervention: 67 (28–86)

Control: 65 (21‐86)

Sex: Male,n (%)

Intervention: 26 (78.8)

Control: 13 (43.3)

other relevant characteristics

Intervention:

SBRT:

48.5 Gy and 30 Gy in 10 daily fractions or

40 Gy and 20 Gy in 5 daily fractions

Control:

Conventional EBRT: 20 Gy in 5 fractions

Or 30 Gy in 10 fractions

Median 10

(5-15) months

The primary objective:

patient‐reported

pain score by two or more points on a visual analog scale (VAS) from 0 to 10 at the treated site 6 months after treatment.

A VAS pain score of 0 with no concomitant increase in OMED was considered to be a complete pain response.

Pain progression was defined as an increase≥2 in the pain score with stable OMED or as pain that was stable or 1 point above the baseline and a ≥25% increase in OMED. Missing pain response assessments were considered as pain progression.

Secondary objectives:

acute (≤3 months after treatment) and late (>3 months after treatment) adverse events graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.03);

Overall survival defined as death from any cause;

Patient‐reported HR-QoL measured using the 5‐level EuroQol Group 5‐dimension QoL questionnaire (EQ‐5D‐5L)

The EQ‐5D‐5L was used together with a VAS from 0 to 100 for rating overall health status (EQ‐VAS).

A vertebral compression fracture was defined as an imaging‐determined decrease in the height of the treated vertebra, regardless of the presence of symptoms.

A change in signal intensity, increased epidural disease, or enlargement of paraspinal disease on control magnetic resonance images (T1-weighted, axial, noncontrast‐enhanced sequence; and T2‐weighted, axial, noncontrast‐enhanced sequence) or an increase in soft‐tissue mass on computed tomography images were documented as radiologic progression.

Risk of bias:

Low for overall survival

Some concerns for other outcomes due to absent of blinding. Details please see the risk of bias table.

Sources of funding:

by Grant KFS‐3956‐08‐2016‐R (Swiss Cancer Research) and by Varian, a Siemens Healthineers

Company.

Study performed in 15 centers in Switzerland, Belgium, Ger-

many, Italy, and Poland

Ryu 2023

Patients who were aged at least 18 years, had a Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) of 0 to 2, and had 1 to 3 treatment naïve vertebral metastases were eligible.

Inclusion criteria:

(1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. Clinically asymptomatic spine metastases detected on screening magnetic resonance imaging (MRI) were included, provided that the lesion was no more than 20% of Each vertebral marrow volume.

Every patient was required to have a baseline pain score of at least 5, using the 0 to 10 Nu-

Merical Rating Pain Scale (NRPS). Pain medication, including narcotics, was allowed. If there were more than 1 spine lesion

With the same maximal pain score, the most cephalad level was considered the index lesion for pain evaluation. Epidural lesions with at least a3-mm gap between the tumor and spinal cord, and paraspinal masses (<5 cm) directly attached to the vertebral body, were eligible. Radioresistant cancers (melanoma, renal cell carcinoma, soft tissue sarcoma) were included.

Patients with systemic or visceral metastases or uncontrolled primary tumors were included when the estimated survival time was longer than 6 months.

Exclusion criteria:

Tumors with vertebral compression fractures with more than 50% height loss and/or bony retropulsion were excluded.

N at baseline

Intervention: n=209/217

Control: n=130/136

Age, Mean (SD) [range]

Intervention: 61.9 (13.1) [23-93]

Control: 63.7 (11.9) [32-91]

Sex, male n (%)

Intervention: Male: 114 (54.5)

Control: 70 (53.8)

Baseline numerical rating pain scale (NRPS)

Median (range)

Intervention: 7 (5-10)

Control: 7 (5-10)

Intervention:

Stereotactic radiosurgery

a single dose of 16

or 18 Gy given to the involved vertebral level(s) only, not including any additional spine levels.

Control:

cEBRT: 8 Gy given

to the involved vertebra plus 1 additional vertebra above and below.

24 months

The primary objective:

Patient-reported pain response at 3 months at the index vertebral level using the NRPS.

Complete response was a pain score of 0 with no increase in narcotic pain medication and no progressive pain at the other treated spine.

Partial response was an improvement to at least

3 points from the baseline pain score, with no increase in narcotic medication. Stable response was defined as the same pain score or within 2 points of the baseline pain score.

Progressive response was an increase of 3 points from the baseline pain score at any treated spine level. Patients with complete or partial pain relief were considered responders.

Patients with complete or partial pain relief at the index site but a progressive response at the secondary site(s) were considered non-responders.

Secondary objectives:

rapidity and duration of

pain response; adverse events (AEs) as measured by the Common Toxicity Criteria Adverse Events, version3.0;

long-term effects on the spinal cord, and vertebral compression fractures on followup spine MRIs.

QoL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G), the Brief Pain Inventory (BPI), and Euro QOL–5 Dimension (EQ-5D), collected at baseline and at 1, 3, 6, and 12 months from randomization.

Duration of pain response, defined as time from complete or partial pain relief to pain

worsening (≥ 3 points); Pain response begins when a patient improves at least 3 points, and pain response ends when the pain score increases by 3 points. Patients assessed at weeks 1, 2, and 3, and 3, 6, 12 and 24 months. Secondary sites are not taken into consideration.

Risk of bias:

Some concerns for overall survival

High for other outcomes due to, absent information about allocation process, absence of blinding, concerns in statistics and result reporting. Details please see the risk of bias table.

Sources of funding:

By grants UG1CA189867 (NCI Community Oncology Research Program) and the Division of Cancer

Prevention from the NCI.

Study performed in US and. internationally.

Hoskin 2024

Patients with metastatic spinal cord compression

Inclusion criteria:

1. Proven diagnosis of spinal cord compression on magnetic resonance imaging (MRI)
2. Histologically or cytologically confirmed malignant disease
3. Life expectancy greater than 1 month
4. Aged 18 years or older
5. Able to give informed consent
6. Willing and able to complete assessment forms

Exclusion criteria:

Patients for whom surgery or chemotherapy treatment is more appropriate
Patient known to be pregnant

In- en Exclusion criteria extracted from the trial registry: ISRCTN97555949.

N at baseline

Intervention: n=341

Control: n=345

Age (mean, SD)

Intervention: reported elsewhere

Control: reported elsewhere

Sex, male

Intervention: reported elsewhere

Control: reported elsewhere

Intervention:

multifraction

radiotherapy

20 Gy in 5 fractions

Control:

single-fraction radiotherapy

a single dose of

8 Gy

12 weeks

The primary objective:

HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30), completed by patients at baseline and at weeks 1, 4, 8, and 12 postrandomization.

Risk of bias:

Low. Details please see the risk of bias table.

Sources of funding:

CRUK Project Grants C2422/7932

and C2422/A11408; Cancer Council Queensland and UK National

Institute of Health Research. PJ Hoskin is supported by NIHR

Manchester Biomedical Research Centre (NIHR203308)

Study performed in UK.

Results

Two RCTs (Guckenberger, 2024; Ryu, 2023) reported the outcome of pain relief, HR-QoL, overall survival, local control, and skeletal related events. Ryu (2023) reported the outcome of duration response. And Hoskin (2024) reported the outcome of HR-QoL (See Summary of Findings).

Search and select

A systematic review of the literature was performed to answer the following question(s):

What are the benefits and risks (in terms of pain relief, local control, mobility, morbidity, mortality and costs) of different radiotherapy techniques (e.g. fractionated versus unfractionated) in patients with spinal metastases?

Table 1. PICO

Patients	Patients with spinal metastases with and without clinical and radiological spinal cord compression
Intervention	Ongefractioneerd (single fraction) conventionele radiotherapie
Control	Comparison between different techniques: gefractioneerde radiotherapie, Intensity Modulated Radiotherapie (IMRT), stereotactische radiotherapie (SBRT), split-course radiotherapie, geen radiotherapie (met of zonder chirurgie)
Outcomes	Pain relief (critical outcome), neurological status including mobility or ambulatory status, and bowel and bladder function (critical outcomes), Health related quality of life (HR-QOL, critical), response duration (important), treatment related morbidity (important), overall survival (important), local control (important), spinal stability (important), skeletal related events (SRE), costs (important)
Other selection criteria	Study design: systematic reviews and randomized controlled trials

Relevant outcome measures

The guideline panel considered pain relief, neurological status (including mobility or ambulatory status, and bowel and bladder function), HR-QOL as a critical outcome measure for decision making; and response duration, treatment related morbidity, overall survival, local control, spinal stability, skeletal related events (SRE), costs as an important outcome measure for decision making.

Table 2. Definitions and thresholds

Outcome	Definition	Threshold
Pain relief/pain response (critical outcome measure)	As defined in the used studies	20% (i.e. 2 punten VAS/NRS (0-10)) Relative ratio ≥1.25 or ≤0.80
neurological status (critical outcome measure)	As defined in the used studies	Relative ratio ≥1.25 or ≤0.80
Quality of life (critical outcome measure)	As defined in the used studies	EQ-5D: >0.08 points EQ-5D VAS: > 7 points (Pickard, 2007) EORTC QLQ-C30: > 5-10 points; >0.3-0.5 SD (Mosoro, 2023) FACT-G total score: > 4-7 points (Yost, 2005)
Response duration (important outcome measure)	As defined in the used studies	Hazard ratio: ≥1.4 or ≤0.7 Relative ratio ≥1.25 or ≤0.80
Treatment-related morbidity (important outcome measure)	As defined in the used studies	Relative ratio ≥1.25 or ≤0.80
SRE (important 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	Hazard ratio: ≥1.4 or ≤0.7 12/16 week depending on life of expectancy
spinal stability (important outcome measure)	As defined in the used studies	Relative ratio ≥1.25 or ≤0.80
costs (important outcome measure)	As defined in the used studies

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 2021 (which is the cutoff year of the NICE guideline) to 14 February 2025 for systematic reviews and RCTs. 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) spinal metastases; (2) radiotherapy. Duplicates were removed using EndNote software. After deduplication a total of 556 records were imported for title/abstract screening. Initially, 80 studies were selected based on title and abstract screening. After reading the full text, 77 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and three studies were included.

1 - Abu-Hegazy M, Wahba HA. Single-versus multi-fraction radiation treatment for metastatic spinal cord compression: functional outcome study. Chin Ger J Clin Oncol 2011;10:535–40.
2 - Bilsky MH, Laufer I, Fourney DR, Groff M, Schmidt MH, Varga PP, et al. Reliability analysis of the epidural spinal cord compression scale: Clinical article. J Neurosurg Spine SPI 2010 Sep 1;13:324–8.
3 - Bindels BJ, Mercier C, Gal R, Verlaan JJ, Verhoeff JJ, Dirix P, Ost P, Kasperts N, van der Linden YM, Verkooijen HM, van der Velden JM. Stereotactic body and conventional radiotherapy for painful bone metastases: a systematic review and meta-analysis. JAMA network open. 2024 Feb 5;7(2):e2355409-.
4 - Chow E, Hoskin P, Mitera G, et al; International Bone Metastases Consensus Working Party. Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys. 2012;82(5):1730-1737. doi:10.1016/j.ijrobp.2011.02.008.
5 - Chow E, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS, Brundage MD, Nabid A, Tissing-Tan CJ, Oei B, Babington S. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. The Lancet Oncology. 2014 Feb 1;15(2):164-71.
6 - De Meerleer G, Khoo V, Escudier B, et al. Radiotherapy for renal-cell carcinoma. Lancet Oncol. 2014;15(4): e170-e177. doi:10.1016/S1470-2045(13)70569-2.
7 - Donovan EK, Sienna J, Mitera G, Kumar-Tyagi N, Parpia S, Swaminath A. Single versus multifraction radiotherapy for spinal cord compression: A systematic review and meta-analysis. Radiother Oncol 2019;134:55–66. https://doi.org/ 10.1016/j.radonc.2019.01.019.
8 - Gal O, Rothrock RJ, Gutierrez AN, Mehta MP, Kotecha R. Stereotactic body radiation therapy versus conventional radiation therapy for painful spinal metastases: a comparative analysis of randomized trials and practical considerations. Practical Radiation Oncology. 2024 Nov 1;14(6):512-21.
9 - 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. Radiother Oncol. 2016 May;119(2):194-201. PMID: 27113796.
10 - Guckenberger M, Andratschke N, Belka C, Bellut D, Cuccia F, Dahele M, Guninski RS, Josipovic M, Mancosu P, Minniti G, Niyazi M. ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases. Radiotherapy and Oncology. 2024 Jan 1;190:109966.
11 - 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.
12 - Hoskin PJ, Reczko K, Rashid M, Hackshaw A, Lopes A, SCORAD Investigators Hopkins K Misra V Holt T McMenemin R McKinna F Krishnaswamy M Bates A O’Rourke N Lester J Sevitt T Roos D Brown G Shibu Thomas S Forsyth S. Quality-of-life outcomes in metastatic spinal cord compression: findings from the SCORAD trial. JNCI: Journal of the National Cancer Institute. 2024 Jul;116(7):1087-94.
13 - Hoskin PJ, Hopkins K, Misra V, Holt T, McMenemin R, Dubois D, et al. Effect of single-fraction vs multifraction radiotherapy on ambulatory status among patients with spinal canal compression from metastatic cancer: The SCORAD randomized clinical trial. JAMA 2019;322:2084.
14 - Howell DD, James JL, Hartsell WF, Suntharalingam M, Machtay M, Suh JH, et al. 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;119:888–96.
15 - Kswig S, Budach V. (Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study). Strahlenther Onkol. 1999 Oct;175(10):500–8.
16 - Lee KA, Dunne M, Small C, Kelly PJ, McArdle O, O’Sullivan J, et al. (ICORG 05–03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis. Acta Oncol 2018;57:965–72.
17 - Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, Romero AM, Nevens D, Palma D, Park C, Ricardi U. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiotherapy and Oncology. 2020 Jul 1;148:157-66.
18 - Maranzano E, Trippa F, Casale M, Costantini S, Lupattelli M, Bellavita R, et al. 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol 2009;93:174–9.
19 - Nguyen QN, Chun SG, Chow E, Komaki R, Liao Z, Zacharia R, Szeto BK, Welsh JW, Hahn SM, Fuller CD, Moon BS. Single-fraction stereotactic vs conventional multifraction radiotherapy for pain relief in patients with predominantly nonspine bone metastases: a randomized phase 2 component of a phase 2/3 trial. JAMA oncology. 2019 Jun 1;5(6):872-8.
20 - Pielkenrood BJ, van der Velden JM, van der Linden YM, Bartels MM, Kasperts N, Verhoeff JJ, Eppinga WS, Gal R, Verlaan JJ, Verkooijen HL. Pain response after stereotactic body radiation therapy versus conventional radiation therapy in patients with bone metastases—a phase 2 randomized controlled trial within a prospective cohort. International Journal of Radiation Oncology* Biology* Physics. 2021 Jun 1;110(2):358-67.
21 - Rades D, Lange M, Veninga T, et al. Preliminary results of spinal cord compression recurrence evaluation (score-1) study comparing short-course versus long-course radiotherapy for local control of malignant epidural spinal cord compression. International journal of radiation oncology, biology, physics. 2009;73(1):228-34.
22 - Rades D, Stalpers LJ, Veninga T, et al. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(15):3366-75.
23 - Rades D, Huttenlocher S, Bajrovic A, et al. Surgery followed by radiotherapy versus radiotherapy alone for metastatic spinal cord compression from unfavorable tumors. Int J Radiat Oncol Biol Phys. 2011;81(5):e861-e868.
24 - Redmond KJ, Sahgal A, Foote M, et al. Single versus multiple session stereotactic body radiotherapy for spinal metastasis: the risk-benefit ratio. Future Oncol. 2015;11(17):2405-2415. doi:10.2217/fon.15.160.
25 - Rich SE, Chow R, Raman S, Zeng KL, Lutz S, Lam H, Silva MF, Chow E. Update of the systematic review of palliative radiation therapy fractionation for bone metastases. Radiotherapy and Oncology. 2018 Mar 1;126(3):547-57.
26 - Ryu S, Deshmukh S, Timmerman RD, Movsas B, Gerszten P, Yin FF, Dicker A, Abraham CD, Zhong J, Shiao SL, Tuli R. Stereotactic radiosurgery vs conventional radiotherapy for localized vertebral metastases of the spine: phase 3 results of NRG Oncology/RTOG 0631 randomized clinical trial. JAMA oncology. 2023 Jun 1;9(6):800-7.
27 - Sahgal A, Myrehaug SD, Siva S, Masucci GL, Maralani PJ, Brundage M, Butler J, Chow E, Fehlings MG, Foote M, Gabos Z. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. The Lancet Oncology. 2021 Jul 1;22(7):1023-33.
28 - Sahgal A, Atenafu EG, Chao S, Al-Omair A, Boehling N, Balagamwala EH, Cunha M, Thibault I, Angelov L, Brown P, Suh J. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. Journal of clinical oncology. 2013 Sep 20;31(27):3426-31.
29 - Soltys SG, Grimm J, Milano MT, Xue J, Sahgal A, Yorke E, Yamada Y, Ding GX, Li XA, Lovelock DM, Jackson A. Stereotactic body radiation therapy for spinal metastases: tumor control probability analyses and recommended reporting standards. International Journal of Radiation Oncology* Biology* Physics. 2021 May 1;110(1):112-23.
30 - Sprave T, Verma V, Förster R, Schlampp I, Bruckner T, Bostel T, Welte SE, Tonndorf-Martini E, Nicolay NH, Debus J, Rief H. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy. Radiotherapy and Oncology. 2018 Aug 1;128(2):274-82.
31 - Sprave T, Hees K, Bruckner T, Foerster R, Bostel T, Schlampp I, et al. The influence of fractionated radiotherapy on the stability of spinal bone metastases: a retrospective analysis from 1047 cases. Radiat Oncol. 2018.
32 - Sprave T, Verma V, Förster R, Schlampp I, Bruckner T, Bostel T, Welte SE, Tonndorf-Martini E, El Shafie R, Nicolay NH, Debus J. Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial) First results of a randomized controlled trial. Strahlentherapie und Onkologie. 2018 Oct;194(10):911-20.
33 - Steenbruggen TG, Schaapveld M, Horlings HM, Sanders J, Hogewoning SJ, Lips EH, Vrancken Peeters MJ, Kok NF, Wiersma T, Esserman L, van ‘t Veer LJ. Characterization of oligometastatic disease in a real-world nationwide cohort of 3447 patients with de novo metastatic breast cancer. JNCI Cancer Spectrum. 2021 Jun 1;5(3):pkab010.
34 - Thirion PG, Dunne MT, Kelly PJ, Flavin A, O’Sullivan JM, Hacking D, Sasiadek W, Small C, Pomeroy MM, Martin J, McArdle O. Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression. British Journal of Cancer. 2020 Apr 28;122(9):1315-23.
35 - Van den Brande R, Thijs D, Bilsky M, Peeters M, Billiet C, Van de Kelft E. Treatment of ambulatory patients with metastatic epidural spinal cord compression: a systematic review and meta-analysis. Journal of Neurosurgery: Spine. 2023 Oct 27;40(2):175-84.
36 - van der Linden YM, Steenland E, van Houwelingen HC, Post WJ, Oei B, Marijnen CAM, et al. Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study. Radiother Oncol 2006;78:245–53. https://doi.org/ 10.1016/j.radonc.2006.02.007.
37 - van der Linden YM, Dijkstra SP, Vonk EJ, Marijnen CA, Leer JW, Dutch Bone Metastasis Study Group. Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. Cancer. 2005 Jan 15;103(2):320-8.
38 - van der Velden JM, Peters M, Verlaan JJ, Versteeg AL, Zhang L, Tsao M, Danjoux C, Barnes E, van Vulpen M, Chow E, Verkooijen HM. Development and internal validation of a clinical risk score to predict pain response after palliative radiation therapy in patients with bone metastases. International Journal of Radiation Oncology* Biology* Physics. 2017 Nov 15;99(4):859-66.
39 - Westhoff PG, De Graeff A, Monninkhof EM, Pomp J, Van Vulpen M, Leer JW, Marijnen CA, Van Der Linden YM, Dutch Bone Metastasis Study Group. Quality of life in relation to pain response to radiation therapy for painful bone metastases. International Journal of Radiation Oncology* Biology* Physics. 2015 Nov 1;93(3):694-701.
40 - Westhoff PG, de Graeff A, Monninkhof EM, et al. Quality of life in relation to pain response to radiation therapy for painful bone metastases. Int J Radiat Oncol Biol Phys 2015; 93: 694–701.
41 - Wilson D, Hiller L, Gray L, et al. The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma. Clinical oncology. 2003;15(7):400-7.
42 - Wong HC, Lee SF, Chan AW, Caini S, Hoskin P, Simone II CB, Johnstone P, van der Linden Y, van der Velden JM, Martin E, Alcorn S. Stereotactic body radiation therapy versus conventional external beam radiotherapy for spinal metastases: A systematic review and meta-analysis of randomized controlled trials. Radiotherapy and Oncology. 2023 Dec 1;189:109914.
43 - Wong HC, Lee SF, Ryu S, Chan AW, Caini S, Johnstone P, van der Linden Y, van der Velden JM, Martin E, Alcorn S, Johnstone C. Impact of recent clinical trials on meta-analysis of stereotactic body radiation therapy for spine metastases and urgent call for consistent study endpoints. Annals of Palliative Medicine. 2025 Mar 30;14(2):15559-159.
44 - Zeng KL, Myrehaug S, Soliman H, Husain ZA, Tseng CL, Detsky J, Ruschin M, Atenafu EG, Witiw CD, Larouche J, da Costa L. Mature local control and reirradiation rates comparing spine stereotactic body radiation therapy with conventional palliative external beam radiation therapy. International Journal of Radiation Oncology* Biology* Physics. 2022 Oct 1;114(2):293-300.

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 is the effectiveness of fluorescence compared to no fluorescence in patients with a suspected high-grade glioma on imaging?

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

Guckenberger, 2024

Probably yes

Reason:

Patients were randomly assigned (1:1) to either SBRT or cEBRT

by the web‐based data capture system secuTrial (Clinical Trials

Center, University Hospital Zurich).

Definitely no

Reason:

open‐label

Definitely no

Reason:

Neither patients nor physicians were blinded to treatment

allocation.

Probably no

Reason: less than half of the patients with complete data after 3 months follow-up:

1 month: 70.5% vs 68.4%;

3 month: 63.6% vs 55.9%;

6 month: 31.3% vs 28.7%;

12 month: 27.2% vs 27.9%;

Probably yes

Reason: All relevant outcomes were reported.

Probably yes

Reason: No other important concern was identified.

Some concerns for outcomes other than overall survival (absent of blinding could have been influenced the measurement of the outcomes)

Low for overall survival

Ryu, 2023

Probably yes

Reason: using permuted-block

Randomization. The influence of randomization in block is uncertain.

Probabl no

Reason: No details about the allocation process.

Definitely no

Reason: There was no blinding of patients or physicians.

Probably yes

Reason: The reason of exclusion after randomization was listed. The potential influence of these exclusion is uncertain.

Probably no

Reason:

All relevant outcomes were reported. It is unclear why 1-sided and 2-sided p value were used for different outcomes.

It is unclear how the between-group difference in proportions of pain response was estimated.

Definitely no

Reason: No other problems noted.

HIGH (Bias in randomization, blinding and some concerns in statistics and results reporting)

Some concerns for overall survival

Hoskin, 2024

Probably yes

Reason:

Bias arizing from the randomisation process in the original RCT Hoskin 2019 is evaluated as low in the NICE guideline.

Probably yes

Reason: Risk of bias due to deviations from the intended interventions (effect of assignment to intervention) in the original RCT Hoskin 2019 is evaluated as low in the NICE guideline.

Probably yes

Reason: Investigators remained blinded to the outcomes throughout the study

Probably yes

Reason: around 70% of the patients with assessment at week 8.

Probably yes

Reason: Relevant outcomes were reported.

Probably yes

Reason: No other problems noted.

LOW

Table of excluded studies

Reference	Reason for exclusion
Evaluation of results and costs of high precision radiotherapy (VMAT) compared with conventional radiotherapy (3D) in the treatment of cancer patients with spinal cord compression of metastatic origin	Wrong study design
Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy for Painful Spinal Metastases: A Comparative Analysis of Randomized Trials and Practical Considerations	The included studies are included in the literatuur analysis
Efficacy and tolerability of single-fraction radiotherapy for spinal bone metastases in a low-middle-income country setting: a prospective study	Wrong study design
An Economic Analysis of SC24 in Canada: A Randomized Study of SBRT Compared With Conventional Palliative RT for Spinal Metastases	Wrong study design
Single versus Multiple Fraction Stereotactic Spine Radiosurgery for Spinal Metastases: A Prospective Randomized Phase II Trial	Verkeerde uitkomst
Local control of bone metastases treated with external beam radiotherapy in recent years: a multicenter retrospective study	Wrong study design
Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN): a randomized phase II study protocol	Wrong study design
Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort	Wrong study population
Remineralization of lytic spinal metastases after radiotherapy	Verkeerde uitkomst
Comparison of 5 √ó 5¬†Gy and 10 √ó 3¬†Gy for metastatic spinal cord compression using data from three prospective trials	Wrong study design
Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial	Wrong study design
Radiotherapy with 15 √ó 2.633 Gy vs. 20 √ó 2.0 Gy in Patients with Malignant Spinal Cord Compression and Favorable Survival Prognoses: A Secondary Analysis of the RAMSES-01 Trial	Wrong study design
Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial	included in the NICE guideline
Outcomes of Palliative Radiotherapy in Metastatic Epidural Spinal Cord Compression in Lung Cancer-A Prospective Observational Study from Tata Memorial Hospital	Wrong study design
Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy	Wrong study design
Treatment of ambulatory patients with metastatic epidural spinal cord compression: a systematic review and meta-analysis	Wrong study design
Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline	Wrong intervention
Stereotactic body radiotherapy versus conventional radiotherapy for painful bone metastases: a systematic review and meta-analysis of randomised controlled trials	The included studies are included in the literatuur analysis
Better pain control with 8-gray single fraction palliative radiotherapy for skeletal metastases: a Bayesian network meta-analysis	Wrong study population
Stereotactic Body Radiation Therapy for Spinal Metastases: Tumor Control Probability Analyses and Recommended Reporting Standards	Wrong intervention
Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Pain Relief for Bone Metastases: A Systematic Review and Meta-Analysis	The included studies are included in the literatuur analysis
Stereotactic body radiation therapy versus conventional external beam radiotherapy for spinal metastases: A systematic review and meta-analysis of randomized controlled trials	The included studies are included in the literatuur analysis
Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control	Wrong study population
Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study	Wrong study design
Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients with Multiple Metastases: Findings from the NRG-BR001 Phase 1 Trial	Wrong study design
Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO)	Wrong study design
Long-Term Results of Dose-Intensified Fractionated Stereotactic Body Radiation Therapy (SBRT) for Painful Spinal Metastases	Wrong intervention
Radiomic modeling to predict risk of vertebral compression fracture after stereotactic body radiation therapy for spinal metastases	Wrong study design
Phase 2 Clinical Trial of Separation Surgery Followed by Stereotactic Body Radiation Therapy for Metastatic Epidural Spinal Cord Compression	Wrong intervention
Randomized phase III study comparing re-irradiation stereotactic body radiotherapy and conventional radiotherapy for painful spinal metastases: Japan Clinical Oncology Group study JCOG2211 (RESCORE study)	Wrong study design
Local Control in Patients with Metastatic Renal Cell Carcinoma to the Spine: The Experience of an Institution with a Multidisciplinary Spine Oncology Program	Wrong intervention
A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases	Wrong intervention
Treatment with Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients with Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial	Wrong intervention
Long-term outcomes of spinal SBRT. Is it important to select the treatment time?	Wrong intervention
Role Of Palliative Radiotherapy In Improving Performance Status And Quality Of Life In Patients With Metastatic Spinal Cord Compression	Wrong intervention
Radiation Therapy for Painful Bone Metastases: Fractionation, Recalcification, and Symptom Control	Wrong study population
Local control and patterns of failure for ‚ÄúRadioresistant‚Äù spinal metastases following stereotactic body radiotherapy compared to a ‚ÄúRadiosensitive‚Äù reference	Wrong study population
The role of radiation therapy in the treatment of spine metastases from hepatocellular carcinoma: a systematic review and meta-analysis	Wrong intervention
Stereotactic body radiotherapy for spinal metastases: a review	Wrong study design
Separation surgery followed by stereotactic ablative radiotherapy for metastatic epidural spinal cord compression: A systematic review and meta-analysis for local progression rate	Wrong intervention
Stereotactic Radiosurgery in Metastatic Spine Disease‚ÄîA Systemic Review of the Literature	Wrong intervention
Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses	Wrong intervention ; verkeerde studie pouplatie
Clinical evaluation, diagnosis, and decision-making for metastatic spine tumors: WFNS spine committee recommendations	Wrong study design
The role of combination surgery and radiotherapy in patients with metastatic spinal cord compression: What are the remaining grey areas? A systematic review	Wrong intervention ; verkeerde studie pouplatie
An Overview of Decision Making in the Management of Metastatic Spinal Tumors	Wrong study design
An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases	Wrong intervention
Stereotactic radiotherapy for bone oligometastases	Wrong study design
Volumetric Intensity-Modulated Arc Stereotactic Radiosurgery Boost in Oligometastatic Patients with Spine Metastases: a Dose-escalation Study	Wrong study design
The Changing Landscape for the Treatment of Painful Spinal Metastases: is Stereotactic Body Radiation Therapy the New Standard of Care?	Wrong study design
Guidelines for Palliative Treatment of Spinal Metastases: Choosing Between Stereotactic Body Radiation Therapy and Conventional Fractionation	Wrong study design
SMILE‚Äîstereotactic multiple fraction radiotherapy for non-spine bone metastases: study protocol for a multicenter, open-label phase III randomized controlled trial	Wrong study population
Impact of National Comprehensive Cancer Network Guidelines Inclusion of Level 1 Evidence on Insurance Denial for Randomized Controlled Trial Patients with Metastatic Spine Disease	Wrong intervention
Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor	Wrong study design
Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial	Wrong study design
Stereotactic body radiotherapy for spinal oligometastases: a review on patient selection and the optimal methodology	Wrong study design
Cost-Effectiveness of Treatment Strategies for Spinal Metastases	Wrong study design
COMPARISION OF TWO DIFFERENT RADIO THERAPY FRACTIONATION SCHEDULES FOR METASTATIC SPINAL CORD COMPRESSION	Wrong study design
Interim analysis of patient-reported outcome compliance and dosimetry in a phase 3 randomized clinical trial of oesophagus-sparing spinal radiotherapy	Wrong study design
Bone-only oligometastatic renal cell carcinoma patients treated with stereotactic body radiotherapy: a multi-institutional study	Wrong study population
Radiotherapy with or without Decompressive Surgery for Metastatic Spinal Cord Compression: A Retrospective Matched-Pair Study including Data from Prospectively Evaluated Patients	Wrong study population
Personalization of Radiation Therapy in the Primary Treatment of Malignant Epidural Spinal Cord Compression (MESCC)	Wrong study design
Second Chance for Cure: Stereotactic Ablative Radiotherapy in Oligometastatic Disease	Wrong study population
Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases: Real-world Outcomes From an International Multi-institutional SBRT Registry	Wrong study design
Shifting the Landscape of Spine and Non-Spine Bone Metastases: A Review of Stereotactic Body Radiotherapy	Wrong study design
Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey	Wrong study design
Dose-Escalated 2-Fraction Spine Stereotactic Body Radiation Therapy: 28 Gy Versus 24 Gy in 2 Daily Fractions	Wrong study design
Narrative review‚Äîdiagnosing and managing malignant epidural spinal cord compression: an evidence-based approach	Wrong study design
External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline	Wrong study design
Stereotactic radiation therapy in the treatment of primary and metastatic tumor lesions of the spine	Wrong study design
Advances in radiotherapy in bone metastases in the context of new target therapies and ablative alternatives: A critical review	Wrong study design
ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases	Wrong study design
Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression: An Updated Meta-analysis	Wrong intervention
Stereotactic body radiotherapy for treatment of spinal metastasis: A systematic review of the literature	The included studies are included in the literatuur analysis
Meta-Analysis of Stereotactic Body Radiation ThERapy in Nonspine BONE Metastases (MASTER-BONES)	Wrong study population
Stereotactic body radiotherapy for non-spine bone metastases: A meta-analysis and international stereotactic radiosurgery society (ISRS) clinical practice guidelines	Wrong study population
Radiation therapy, radiosurgery, chemotherapy and targeted therapies for metastatic spine tumors: WFNS Spine committee recommendations	Wrong study design
Emergent radiotherapy for spinal cord compression/impingement√¢‚Ç¨"a narrative review	Wrong study design

Beoordelingsdatum en geldigheid

Publicatiedatum : 05-06-2026

Beoordeeld op geldigheid : 05-06-2026

Initiatief en autorisatie

Initiatief:

Nederlandse Vereniging voor Neurologie

Geautoriseerd door:

Nederlandse Federatie van Kankerpatiëntenorganisaties
Nederlandse Internisten Vereniging
Nederlandse Orthopaedische Vereniging
Nederlandse Vereniging voor Anesthesiologie
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
Nederlandse Vereniging voor Neurologie
Nederlandse Vereniging voor Nucleaire geneeskunde
Nederlandse Vereniging voor Radiotherapie en Oncologie
Nederlandse Vereniging voor Radiologie
Stichting Darmkanker
Verpleegkundigen en Verzorgenden Nederland
Nederlandse Vereniging van Revalidatieartsen

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 KWF Kankerbestrijding PRESENT+: merging and expanding cohorts into a national realworld prospective cohort to improve symp ZonMw The BLEND trial – stereotactic body radiotherapy followed by surgical stabilization within 24 hours	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) Co-founder SentryX (www.sentryx.nl), chief medical officer (0.6 Fte). Als CMO ben ik verantwoordelijk voor het medische/klinische gedeelte van de taken binnen de start-up. We ontwikkelen 'implantable anesthetics'; oplosbare slow-release depots, met een lokaal anestheticum als actieve stof, voor de behandeling van postoperatieve pijn.	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. EU METASTRA: Predictieve modellen, AI, wervelmetastasen ZonMW BLEND RCT: Radiotherapie en chirurgie voor wervelmetastasen combineren op dezelfde dag Hanarth Fonds PREVECAIMM: Predictieve modellen, AI, wervelmetastasen KWF CODED: Ontwikkeling hemostatische hydrogel voor glioblastoom chirurgie Philips PhD Project: Navigatie in spinale chirurgie	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 UMC Utrecht	geen	geen	geen	ja Foundation STOPbraintumors.org effect tumorgroei bij zwangerschap bij vrouwen met laaggradige gliomen BMS BET remmer in combinatie met standaard chemoradiatie als eerste lijnbehandeling bij glioblastoom Novartis LAG remmer na falen immuuntherapie bij solide tumoren EORTC marizomib bij standaard chemoradiatie bij glioblastoom Pfizer en Ipsen Pharma compassionate use medicatie	geen	BMS Advisory Board; Faculty member ESMO CNS tumors; Quality of Care commission Dutch Society of Medical Oncology; Quality Assurance commission EORTC	20-12-2023	Geen restrictie. (In de richtlijn worden geen systemische therapien aanbevolen.)
Maaike Schippers	Radiotherapeut Werkgever: Helios	geen	geen	geen	geen	geen	geen	3-12-2023	Geen restrictie
Marthe Paats	Longarts Erasmus MC	geen	Geen relevant voor huidige richtlijn. Vergoedingen ten alle tijden naar werkgever Betaalde adviesraden in afgelopen 3 jaar: Eli Lilly: internationale adviesraad EGFR+ NSCLC Amgen: adviesraad KRAS G12C+ NSCLC Pfizer: adviesraad TKI's in NSCLC Merck: adviesraad MET exon 14 skipping mutatie + NSCLC J&J: adviesraad EGFR exon 20 mutaties in NSCLC	geen	industrie gesponsorde studies lopend in het Erasmus MC waarbij ik lokale PI ben. Geen relevant voor huidige richtlijn. Vergoedingen ten alle tijden naar werkgever Astra Zeneca ORCHARD studie (fase 2 studie, progressie na 1L osimertinib) Abbvie M16-573 (fase 1 studie ABBV-155 +/- taxane in NSCLC/SCLC/mammaca) Navire Pharma Inc. NAV-1003 (fase 1 studie met BBP-398 en sotorasib bij KRAS G12C+ NSCLC) GSK NY-ESO (fase 1 studie NY-ESO TCR)	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 Radboudumc te Nijmegen	Medisch Adviseur	geen	nee	geen	net ontwikkelaar van een predictiemodel dat genoemd wordt in richtlijn	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 Rijndam	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 sponsor Sanquin; gerandomiserd onderzoek naar3-versus5-donoren bloedplaatjesconcentraat	geen	nvt	04-05-2024	Geen restrictie
Van Iterson	AIOS neurologie ETZ Tilburg	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 vrijwilliger team PPO (patiëntenparticipatie bij wetenschappelijk onderzoek)	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 Let's beat NF (Stichting NF) MEK remmers bij NF1 NFVN (NF ver Ned) MEK remmers bij NF1 Novartis MEK remmers bij NF1	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 Anesthesioloog Pijnspecialist	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
Radiotherapy	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: UV4 Welke bestralingstechniek, inclusief de keuze tussen gefractioneerde en ongefractioneerd radiotherapie, wordt aanbevolen voor patiënten met wervelmetastasen zonder en met myelumcompressie?
Database(s): Embase.com, Ovid/Medline all	Datum: 14 februari 2025
Periode: vanaf 2021 (NICE guideline)	Talen: geen restrictie
Literatuurspecialist: Alies Oost	Rayyan: https://new.rayyan.ai/reviews/1326084/screening
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: spinal metastases radiotherapy De sleutelartikelen worden gevonden met deze search, m.u.v. ‘Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status among Patients with Spinal Canal Compression from Metastatic Cancer: The SCORAD Randomized Clinical Trial/ Hoskin P.J. (2019)’ doordat er is gezocht vanaf 2021.
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 February 14^th, 2025 for systematic reviews and RCTs. 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) spinal metastases; (2) radiotherapy. Duplicates were removed using EndNote software. After deduplication a total of 556 records were imported for title/abstract screening.

Zoekopbrengst

	EMBASE	OVID/MEDLINE	Ontdubbeld
SR	240	116	250
RCT	268	113	306
Totaal	508	229	556*

_{*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 mescc:ti,ab,kw OR mscc:ti,ab,kw	30356
#2	'radiotherapy'/exp OR 'radiosurgery'/exp OR 'radiotherap':ti,ab,kw OR radiosurg:ti,ab,kw OR 'radio surg':ti,ab,kw OR irradiat: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 OR 3dcrt:ti,ab,kw OR '3d crt':ti,ab,kw	1484226
#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) AND [2021-2025]/py	2303
#4	'meta analysis'/exp OR 'systematic review'/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	1079981
#5	'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	4206802
#6	#3 AND #4	240
#7	#3 AND #5 NOT #6	268
#8	#6 OR #7	508

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 mescc.ti,ab,kf. or mscc.ti,ab,kf.	15574
2	exp Radiotherapy/ or 'radiotherap'.ti,ab,kf. or radiosurg.ti,ab,kf. or 'radio surg'.ti,ab,kf. or irradiat.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. or 3d?crt.ti,ab,kf.	959222
3	(1 and 2) not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/)	5485
4	limit 3 to yr="2021 -Current"	1156
5	exp Meta-Analysis/ or exp Network Meta-Analysis/ or exp Systematic Review/ 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.	806128
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.	2843703
7	4 and 5	116
8	(4 and 6) not 7	113
9	7 or 8	229

Wervelmetastasen

Wervelmetastasen

Uitgangsvraag

Aanbeveling

Overwegingen

Onderbouwing

Achtergrond

Conclusies / Summary of Findings

Samenvatting literatuur

Zoeken en selecteren

Referenties

Evidence tabellen

Verantwoording

Beoordelingsdatum en geldigheid

Initiatief en autorisatie

Algemene gegevens

Samenstelling werkgroep

Belangenverklaringen

Inbreng patiëntenperspectief

Werkwijze

Zoekverantwoording

Bijlagen

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