How to select a treatment method for patients with potentially unstable metastatic vertebrae (spinal instability neoplastic score 7–12): a systematic review

Tue Helme Kildegaard; Daniel Sabroe; Miao Wang; Kristian Høy

doi:10.31616/asj.2025.0078

Kildegaard, Sabroe, Wang, and Høy: How to select a treatment method for patients with potentially unstable metastatic vertebrae (spinal instability neoplastic score 7–12): a systematic review

Review Article

Asian Spine Journal 2025;asj.2025.0078.

Online first: September 19, 2025

DOI: https://doi.org/10.31616/asj.2025.0078

How to select a treatment method for patients with potentially unstable metastatic vertebrae (spinal instability neoplastic score 7–12): a systematic review

Tue Helme Kildegaard¹

, Daniel Sabroe²

, Miao Wang^2,³

, Kristian Høy^2,^3,⁴

¹Aarhus University, Aarhus, Denmark

²Spine Section, Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark

³Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

⁴Department of Biomedicine, Aarhus University, Aarhus, Denmark

Corresponding author: Kristian Høy, Spine Section, Department of Orthopaedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark,
Tel: +45-20205058, Fax: +45-20105058, E-mail: kwhoey@biomed.au.dk

Received February 9, 2025 Revised May 5, 2025 Accepted May 19, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The spinal instability neoplastic score (SINS) is used to evaluate spinal stability in patients with metastatic vertebrae and to guide treatment selection. SINSs of 13–18 indicate instability typically requiring surgery, while SINSs of 1–6 indicate stability and suitability for radiotherapy. However, the optimal approach for patients with SINSs of 7–12 remains unclear. This systematic review aimed to determine the optimal primary treatment for patients with intermediate SINSs (7–12) and potentially unstable metastatic vertebrae. A systematic literature search was conducted in PubMed, Embase, and Scopus, following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Twenty-six studies were included in this review (three A-class and 23 B-class). The A-class studies showed better outcomes with surgery±radiotherapy than radiotherapy alone. Two B-class studies indicated that patients with SINSs ≥10 more frequently underwent surgery, and one study found surgery was less effective for SINSs ≤9. Four studies showed good outcomes of surgery. In another study, 30% of patients became unstable after radiotherapy. In four studies, vertebral compression fractures developed in 20%–30% of patients after stereotactic body radiation therapy or stereotactic ablative body radiotherapy. One study showed that SINSs of 7–12 were correlated with radiotherapy failure, while another study found no such association. This systematic review suggests that surgical intervention alone or in combination with radiation may be superior for patients with SINSs of 7–12 and metastatic spinal tumors. The SINS 7–12 category might be divided into subgroups where surgery or radiotherapy is optimal. SINS ≥10 may indicate a need for surgery, and individual SINS components could be predictive. Further research is warranted to obtain more definitive evidence.

Keywords: Spinal cord compression; SINS-score; Surgery; Oncology; Metastasis

Introduction

Spinal metastases occur in approximately 15.67% of living patients with solid tumors, and autopsy studies have shown that they are present in up to 30% of patients at the time of their death [1]. In some cases, cancer patients present with spinal metastasis as their initial symptom [2]. The most common primary cancers leading to spinal metastases are prostate, lung, breast, and kidney cancers [3]. The median age of patients with spinal metastases is 65 years [4,5]. The distribution of spinal metastases varies by spinal region, with 60%–80% affecting the thoracic spine, 15%–30% the lumbar spine, and 10 % the cervical spine [3]. The incidence of symptomatic spinal metastases is increasing, likely due to aging populations and improved cancer survival rates [6].

Symptoms of spine metastasis include mechanical, local, and radicular pain. Approximately 5%–10% of patients with spinal metastases develop metastatic spinal cord compression (MSCC) [7], a condition that constitutes an acute oncologic emergency requiring prompt surgical intervention. MSCC can be partial or complete, potentially leading to loss of sensation, paralysis, and sphincter dysfunction below the lesion [8]. Treatment for spinal metastases typically involves surgery with adjuvant radiotherapy or radiotherapy alone.

The most common surgical techniques for spinal metastasis include decompression and fixation with a pedicle screw system [4]. Radiotherapy options include conventional external beam radiation therapy (EBRT) and stereotactic body radiation therapy (SBRT), delivered in various doses and fractionations [9]. Both surgery and radiotherapy have proven effective in treating spinal metastases [10].

The spinal instability neoplastic score (SINS) was developed in 2010 to assess spinal stability and predict the need for surgical stabilization [11]. This 18-point system evaluates five radiographic parameters and pain types: spinal level of the lesion, presence and type of pain, bone quality of the lesion, spinal alignment, extent of vertebral body collapse, and posterolateral involvement of spinal elements. Scores are categorized as follows: 0–6 indicates stability, 7–12 suggests potential instability, and 13–18 indicates instability. Generally, stable lesions (SINS 0–6) do not require surgical treatment, whereas unstable lesions (SINS 13–18) typically do, although exceptions exist. The optimal management of potentially unstable lesions (SINS 7–12) is debatable, but surgical consultation is recommended.

Murtaza and Sullivan [12] conducted a review demonstrating that SINSs can standardize the diagnosis of spinal instability and facilitate timely referrals for surgical intervention. Additionally, SINSs may help identify patients who would particularly benefit from radiotherapy [12].

Recent advances in radiotherapy and surgical techniques have significantly improved clinical outcomes for patients with spinal metastases [13], yet optimal treatment strategies for patients with intermediate SINSs of 7–12 remain unclear. Given that most patients with spinal metastases fall within this category [14], further evidence is needed to inform treatment selection. Some potentially unstable lesions may eventually stabilize with radiotherapy, while others may progress to instability, necessitating surgical intervention.

This study aimed to investigate the selection of primary treatment modality (radiotherapy or surgery) for patients with potentially unstable metastatic vertebrae (SINS 7–12).

Materials and Methods

Search strategy

We conducted a systematic literature search following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines [15]. A PRISMA flow diagram illustrating the study identification, screening, eligibility, and inclusion process is presented in Fig. 1, which also details the search strings used. The literature search was conducted in April 2025, encompassing studies published up to and including 2024 across multiple databases: PubMed (2.365 results), Scopus (1,874 results), and Embase (2,268 results). A broad search strategy was employed to ensure comprehensive coverage of relevant literature.

After removing duplicates, studies were screened based on the following predefined inclusion criteria: (1) original research articles; (2) English-language full-text availability; (3) patients with spinal metastases and SINSs of 7–12; (4) evaluation of clinical outcomes following surgery and/or radiotherapy. Potentially relevant articles identified through title and abstract screening underwent full-text review. Studies meeting the inclusion criteria were included in the analysis.

The included studies were categorized into two groups. Group A comprised A-class literature comparing the effects of surgery and radiotherapy for patients with SINSs of 7–12. Group B comprised B-class literature that evaluated the effects of either surgery or radiotherapy for patients with SINSs of 7–12, including those who were examined as part of a subgroup analysis.

Quality assessment

The Effective Public Health Practice Project (EPHPP) tool was used to standardize quality assessment of included studies, evaluating selection bias, study design, confounders, blinding, data collection methods, and withdrawals/dropouts [16,17]. Individual components were graded as “weak,” “moderate,” or “strong” based on reference articles [16,17], focusing on studies analyzing treatment effects for the SINS 7–12 group. Global ratings were assigned as follows: strong (no weak rating), moderate (one weak rating), and weak (more than one weak rating). The review protocol, including review questions, search strategy, inclusion criteria, and risk of bias assessment, was established prior to conducting the review.

Results

The literature search is summarized in a PRISMA flow diagram (Fig. 1) [15]. After screening, 4,363 studies were excluded for not meeting the inclusion criteria. A further 70 studies were excluded after full-text review: 68 for not separately analyzing the SINS 7–12 group, one for not involving actual patients [18], and one for focusing solely on kyphoplasty. No additional studies were identified through screening of reference lists. Ultimately, 26 studies were included in the review, with characteristics presented in Tables 1 (Group A) and 2 (Group B). Three studies were grouped as A-class literature [14,19,20], while 23 were grouped as B-class literature [21–43].

A-class literature results

The A-class literature provided the best evidence, as these studies compared surgery and radiation or a combination thereof for the SINS 7–12 group.

Dial et al. [19] conducted a retrospective study of 211 patients with SINSs of 7–12, comparing outcomes of EBRT alone (n=128), surgery+EBRT (S+E, n=57), or cement augmentation+EBRT (K+E, n=27). The study found significant differences in length of survival (LOS): 430 days in the S+E group, 169 days in the K+E group, and 121 days in the EBRT alone group (p<0.001). Ambulation retention at death was highest in the K+E group (92%), followed by the S+E group (91%) and the EBRT group (77%; p<0.01). Additionally, revision treatment rates at the same spinal level differed significantly: 17.5% for the S+E group, 7.7% for the K+E group, and 20.3% for the EBRT alone group (p<0.04). The study concluded that combining surgical management with radiation therapy improved LOS, ambulation retention, and reduced revision treatment rates compared to radiation therapy alone, supporting surgical intervention alongside radiation for patients with SINSs of 7–12.

Versteeg et al. [14] conducted an international prospective, multicenter study of 200 patients with metastatic spinal tumors and SINSs of 7–12, comparing surgery±radiation (n=136) to radiation alone (n=84). After 12 weeks, surgically treated patients showed a 3.0-point decrease in the Numeric Rating Scale (NRS) pain score (p<0.001) and a 12.7-point increase in the health-related quality of life (HRQOL) (Spine Oncology Study Group Outcomes Questionnaire 2.0 [SOSGOQ2.0] score, p<0.001). Patients treated with radiotherapy alone showed a 1.4-point decrease in NRS pain score (p=0.046) and a non-significant 6.2-point increase in SOSGOQ2.0 score (p<0.331) at 12 weeks. Notably, surgically treated patients maintained significant improvements in pain and HRQOL at 52-week follow-up, whereas radiotherapy-alone patients did not. These findings also favor surgery alone or in combination with radiotherapy for the SINS 7–12 group.

Vargas et al. [20] conducted a retrospective review of 162 patients with metastatic spinal tumors (SINSs of 7–12), comparing surgical treatment (n=63) to radiation alone (SBRT or EBRT, n=99). They measured Karnofsky Performance Scale (KPS) scores and Eastern Cooperative Oncology Group Performance Status (ECOG) pre- and post-treatment, with mean follow-up times of 1.9 years for the surgical cohort and 2 years for the radiation cohort. After accounting for covariates, the average post-treatment change in KPS scores in the surgical cohort and radiation cohort was 7.46±17.3 and −2±13.6, respectively (p=0.045). KPS scores improved in 60.3% of surgical patients and 32.3% of radiation patients. However, there were no significant differences in the ECOG scores. The study’s subanalysis of the radiation group found no difference in fracture rates between SBRT and EBRT. However, 21.2% of patients treated with radiation developed vertebral compression fractures (VCFs) at the treated level. The researchers concluded that surgical intervention for patients with SINSs of 7–12 resulted in improved KPS scores compared to radiation alone, indicating that radiation alone can lead to VCFs.

B-class literature results

The B-class literature results are summarized in Table 2, with key findings described in the following sections.

Pennington et al. [31] suggested a potential cutoff value within the SINS 7–12 range, which could guide treatment decisions. They proposed that lesions with SINS scores of 9 or less might not require stabilization, and potentially unstable cases could be reclassified as stable or unstable, eliminating the “potentially unstable” category [31]. Hussain et al. [32] found that patients with SINSs of 10–12 experienced significantly greater reductions in pain and disability patient-reported outcomes scores after surgery than patients with SINSs of 7–9. Versteeg et al. [44] compared the SINSs in a multi-institutional series of 1,509 patients who underwent surgery or radiotherapy. The researchers found significantly higher scores in the surgical group (mean 10.7 vs. 7.2). However, the study included patients with neurological impairment, a condition that requires surgery. Vargas et al. [26] found higher SINSs in surgical patients compared to non-surgical patients and suggested a potential cutoff value >10 for surgical consideration. Kim et al. [28] found no significant correlation between SINS subgrouping (7–12) and the need for conversion to surgery after initial conservative therapy.

Four studies included in this review showed that VCFs developed in 19%–30% of patients after SBRT or stereotactic ablative body radiotherapy (SABR) [23,38,42,43]. Additionally, two studies yielded contradictory results regarding the association of SINSs of 7–12 and radiotherapy failure; one found such an association [41], and the other did not [22]. A meta-analysis by Kim et al. [45] suggested increasing the SINS cutoff value to better predict VCFs. Lam et al. [39] found that patients with SINSs ≥11 had 2–5 times higher odds of spinal adverse events after SBRT compared to those with scores ≤10.

Revising the SINS components could enhance treatment guidance. Kim et al. [28] found that patients with <50% vertebral body collapse or tumors in the semirigid region (T3–T10) had increased need for conversion to surgery after initial conservative treatment, suggesting that surgery might be preferable for SINS 7–12 patients with these factors. Similarly, other studies suggest that lytic lesions may indicate greater instability, potentially guiding treatment decisions toward surgery for SINS 7–12 patients [46,47]. Pennington et al. [31] found that lesion quality, lesion-associated pain, vertebral height loss, and posterior body involvement were significantly associated with stabilization.

Quality Assessment Results

Selection bias

One study received a strong rating because it included all neurologically intact patients in the SINS 7–12 groups [31]. Three studies categorized as A-class literature, received moderate ratings due to differences in baseline characteristics between patients selected for surgery and those selected for radiotherapy [14,19,20]. Seventeen studies received moderate ratings because they analyzed the effects of either surgery or radiotherapy [22,24,26–30,32–37,39,41–43]. Five studies received weak ratings due to limitations such as focusing only on specific cancer types or cohorts that did not fit the SINS 7–12 group, which restricted their generalizability to the broader SINS 7–12 population [21,23,25,38,40].

Study design

The study designs included 20 retrospective cohort studies, five prospective cohort studies, and one retrospective case-control study (Table 3). Although all received “moderate” ratings, the prospective studies had a stronger design due to their prospective nature.

Confounders

The potential confounders assessed in the included studies are presented in Tables 1 and 2. Twenty studies received strong ratings for presenting relevant baseline characteristics and controlling for imbalances in the analyses and designs (where relevant) [14,19–24,26–30,33,34,36,38–42]. Wänman et al. [25] controlled for some confounders, but missed some relevant characteristics, such as the rTokuhashi score, resulting in a moderate rating. Six studies received weak ratings because they presented several potentially confounders but did not clearly indicate whether these confounders were included in the analysis [31,32,35,37,43].

Blinding

Blinding was rated as moderate across all studies since none of the authors provided complete blinding descriptions. In retrospective studies, participants were likely unaware of the research questions. Blinding is crucial for subjective outcomes like pain or HRQOL, but less critical for objective parameters like survival or VCF. Some studies mentioned blinding but did not provide sufficient information for a strong or weak rating, making it difficult to assess the extent of blinding [14,25,32,41].

Data collection

The data collection rating was based on whether the methods used were valid and reliable. The validity of SINS evaluations has been assessed in several studies. Two studies [30,37] evaluating changes in SINS groups were rated strong, with Gallizia et al. [37] using a validated Visual Analog Scale for evaluating pain responses [48]. Twenty-two studies that measured outcomes such as LOS, ambulation, mean survival, and VCF were rated as strong [19–23,25–29,31–33,35,36,38–43]. Hussain et al. [32] received a strong rating for using the Brief Pain Inventory and MDASI-SP to assess patient-reported outcomes. Three studies received moderate ratings due to partially validated tools or limited reliability confirmation [14,24,34].

Withdrawals and dropouts

The assessment of withdrawals and dropouts did not apply to the only retrospective case-control study [41]. Twenty studies were rated strong with follow-up rates ≥80% [22–29,31,33,35–40,42,43]. Three studies received moderate ratings due to withdrawal rates lower than 79% [14,21,32]. Two studies received weak ratings: Dakson et al. [30] for a 48% follow-up rate and Masuda et al. [34] for an insufficient description of withdrawals and dropouts.

Global Score

Fifteen studies received strong global ratings, 11 received moderate global ratings, and none received weak ratings (Table 3). None of the studies were excluded following the quality assessment.

Discussion

Interpretation of the results in the context of other evidence

When interpreting evidence regarding treatment selection for the 7–12 SINS group, A-class literature, which compared surgery and radiotherapy effects, was valued higher than B-class. The three A-class studies were conducted by Dial et al. [19], Versteeg et al. [14], and Vargas et al. [26], respectively. Dial et al. [19] found that combined surgical management and radiotherapy improved outcomes, including LOS, ambulation, and revision treatment rates, compared to radiotherapy alone. Versteeg et al. [14] found that surgically treated patients had clinically and statistically significant improvements in pain and HRQOL up to 1 year after surgery, whereas patients treated with radiotherapy alone did not maintain these effects. Vargas et al. [20] found that the average KPS improved more in the surgery group than in the radiation group, suggesting surgery might be a better treatment option for the SINS 7–12 group. However, there is a potential selection bias, as patients chosen for surgery might be different from those chosen for radiotherapy. Patients receiving radiotherapy alone might be less medically fit, which could explain the smaller improvements seen in that group. Dial et al. [19] tried to address potential biases by conducting a subgroup analysis of patients with rTokuhashi scores >8 (expected survival >6 months). Even in this subgroup, surgical stabilization with adjuvant radiotherapy showed better outcomes, including prolonged survival and improved ambulation, compared to radiotherapy alone.

Versteeg et al. [14] identified distinct clinical profiles in SINS 7–12 patients treated with surgery or radiotherapy. Surgically treated patients had more radioresistant tumors, worse ECOG-PS, a higher prevalence of minor neurological deficits, higher median SINSs (9.5 vs. 8), and a greater proportion of lytic tumors and mechanical pain. Dial et al. [19] found that patients receiving surgical stabilization before radiotherapy were younger, had better predicted survival, and had more radiation-resistant tumors. This suggests that differences in patient characteristics might have influenced treatment outcomes, making it uncertain whether radiotherapy patients would have benefited from surgery. The evidence discussed in this article suggests that surgery is an option for SINS 7–12 patients and can improve their HRQOL. Combined surgery and radiation also show promise. While radiation alone provides some improvement, it carries a higher risk of VCFs. Direct comparisons suggest that surgery±radiation is superior to radiation alone.

Importantly, SINSs alone are not sufficient for treatment decision-making in patients with spinal metastases; they are only suitable for evaluating spinal stability. Other factors not covered by the SINS might also play important roles [6]. Impaired neurological function should, in most cases, lead to surgery. A poor performance score and low expected survival time (less than 3 months) often lead to radiotherapy. Moribund patients may only receive palliative end-of-life care. Other key factors include the tumor’s radiosensitivity and chemosensitivity. Ultimately, treatment decisions should be patient-centered, taking into account individual needs and circumstances. A survey conducted by Catanzano et al. [18] revealed uncertainty regarding surgical decision-making for patients with SINS 7–12, even among experienced physicians dealing with high volumes of cases. Dial et al. [19] suggest that the need for spinal stabilization in addition to radiotherapy for these patients should be discussed in a multidisciplinary setting.

LMNOP framework is a decision-making tool that incorporates SINSs [49]. It comprises key factors that should be considered while determining the optimal treatment for spinal metastasis: the location of the disease in the spine (L), mechanical instability as graded by SINS (M), neurological status (N), oncology (particularly regarding radiosensitivity, O), and the patient’s fitness, wishes, prognosis, and response to prior therapy (P). NOMS is another decision-making framework [50]. However, it does not incorporate SINSs as a way of describing mechanical instability, but only in the context of movement-related pain. LMNOP provides a systematic but individualized approach to treatment decision-making for patients with spinal metastases.

Kwan et al. [51] recently reviewed current approaches for managing metastatic spine patients, with findings largely consistent with this article’s conclusions, but also several notable differences. Most notably, Kwan et al. [51] included 17 studies encompassing patients with both intermediate (SINS 7–12) and high (SINS 13–18) spinal instability, thereby broadening the patient population and potentially introducing treatment strategies not specifically tailored to the intermediate group. In contrast, the present review exclusively focused on studies involving patients with intermediate spinal instability (SINS 7–12), offering a more targeted analysis of this clinically ambiguous category. Furthermore, Kwan et al. [51] focused on comparing various surgical techniques for SINS 7–12 patients, while the present review evaluated surgery as a whole versus radiotherapy. This allowed for a broader examination of the choice between operative and nonoperative management. Our analysis was structured by dividing studies into two categories: (A) direct comparisons of surgery and radiotherapy, and (B) studies focusing on outcomes of either surgery or radiotherapy independently. Moreover, the EPHPP tool was used to assess the methodological quality of included studies, adding transparency and rigor to the review. Despite these methodological differences, both reviews highlighted the scarcity of high-quality evidence available and the need for further research to inform optimal treatment strategies for this patient population.

Limitations of the included evidence

The external validity of the studies was limited by selection bias, as previously discussed. The absence of randomized controlled trials (RCTs) increased the risk of bias. However, RCTs might be challenging in this context due to ethical concerns and the need for individualized decision-making. The SINS 7–12 study populations in the included studies were generally small, with only three studies involving more than 200 patients [14,19,42]. One study evaluated only 24 SINS 7–12 patients, which limited the statistical power [34]. One study focused exclusively on patients with prostate cancer who were surgically treated for MSCC [25], limiting its utility for informing treatment selection for patients with SINSs of 7–12. MSCC, which involves neurological impairment, almost always leads to surgery, and prostate cancer is only one of the cancers that can lead to spinal metastases. The studies assessed varied outcomes, limiting cross-study comparisons. The primary goal of treatment for spinal metastases is to preserve patients’ HRQOL [6]. This goal is achieved by reducing pain, preserving ambulation ability, and maintaining sphincter functions. Therefore, it can be argued that the most valuable outcome measures are HRQOL, ability to ambulate, pain, disability/activity, neurologic status, LOS, and performance status, while changes in SINS status, VCF development, and revision treatment are less valuable.

Limitations of the review

This review was limited by the scarcity of relevant articles, precluding statistical meta-analyses and forest plots. Potential publication bias may have contributed to missing data. Additionally, the review could only compare surgery and radiotherapy broadly, without differentiating between specific methods. Lastly, varying outcome measures made it impractical to combine study results statistically.

Conclusions

Implications of the results for practice, policy, and future research

This systematic review highlights the superiority of surgical intervention, either alone or in combination with radiation, for patients in the SINS 7–12 categories with metastatic spinal tumors. However, treatment decisions should consider multiple factors beyond SINS, including performance score, expected survival, primary tumor type, radiosensitivity, and neurologic function. The SINS 7–12 group may be heterogeneous, with some patients benefiting more from surgery and others from radiotherapy. A cutoff value of ≥10 might better predict the need for surgery. Additionally, some of the individual SINS components might have predictive value, suggesting a more nuanced approach to treatment decision-making. Future studies should compare treatment effects for the 7–12 SINS group, ideally through multi-institutional prospective cohort studies. These studies should measure important outcomes, such as HRQOL, pain, ambulation, and LOS, thus employing a multidisciplinary team approach to generate data.

Key Points

Surgical intervention is superior.
A cutoff value ≥10 may better predict the need for surgery.
A spinal instability neoplastic score ≥10 indicates a need for surgery.
Surgery improved health-related quality of life.
More uniform meta-analyses are needed.

Notes

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Author Contributions

Conceptualization: KH, THK. Data curation: THK, DS. Formal analysis: THK, DS. Investigation: THK, DS, MW, KH. Methodology: KH, MW. Project administration: KH. Supervision: KH, MW. Validation: KH, MW. Visualization: THK, DS. Writing–original draft: THK, DS. Writing–review & editing: KH, MW. Final approval of the manuscript: all authors.

Fig. 1

Search strategy: PubMed and Embase: (Metastatic OR Neoplastic) AND (Spinal OR Spine) AND (Instability OR SINS OR Fractures, Compression) AND (Spinal fusion OR Surgery OR radiotherapy). Scopus: ((metastatic OR neoplastic) AND (spinal OR spine) AND (instability OR sins OR fracture) AND (fusion OR surgery OR radiotherapy)). SINS, spinal instability neoplastic score.

Table 1

Group A (A-literature): directly compares the effects of surgery and radiotherapy in SINS 7–12 patients

Study	Study design	Study population (only patients with SINS 7–12)	Exposure (initial treatment)	Outcomes measured	Potential confounders assessed	Results
Dial et al. [19] (2022)	Retrospective cohort study	211 neurologically intact patients	EBRT only, surgery + EBRT (S+E) or cement augmentation + EBRT (K+E)	LOS Ability to ambulate Revision treatment	rTokuhashi score, performance score, age, gender, mean SINS	LOS was 430 days in the S+E group, 169 days in the K+E group and 121 days in the EBRT group 91% of patients in the S+E group, 92% of patients in K+E group and 77% of patients in the EBRT group retained the ability to ambulate at their time of death. Revision treatment at the spinal level initially treated was 17.5% for the S+E group, 7.7% for K+E group and 20.3% for the EBRT group.
Versteeg et al. [14] (2021)	Prospective cohort study	220 neurologically intact patients	Radiotherapy alone or surgery +/− radiotherapy	HRQOL Pain	Gender, primary tumor, pain, performance status, epidural spinal cord compression	Surgically treated patients had a 3.0-point decrease in NRS pain score (p>0.001) and a 12.7-point increase in SOSGOQ2.0 score (p<0.001) after 12 weeks Radiotherapy alone treated patients had a 1.4-point decrease in NRS pain score (p=0.046) and 6.2-point increase in SOSGOQ2.0 score (p<0.331) after 12 weeks The significant improvements in pain and HRQOL were maintained in the 52-week follow-up for surgically treated patients, but not for the radiotherapy alone treated patients.
Vargas et al. [20] (2023)	Retrospective cohort study	162 ESCC grade 3 were excluded	Radiation alone (EBRT or SBRT) or surgery alone	KPS score ECOG score	Age, gender, sex, tumor type and location, pain, lytic or blastic bone lesion	Average posttreatment changes in KPS: surgical cohort=7.46±17.3 and radiation=–2±13.6 (p=0.045) KPS improved in 60.3% of cases in the surgical group compared to 32.3% in radiation group. 21.2% of patients in the radiation group eventually developed VCF.

SINS, spinal instability neoplastic score; EBRT, external beam radiation therapy; LOS, length of survival; HRQOL, health-related quality of life; NRS, Numeric Rating Scale; SOSGOQ2.0, Spine Oncology Study Group Outcomes Questionnaire 2.0; ESCC, epidural spinal cord compression; SBRT, stereotactic body radiation therapy; KPS, Karnofsky Performance Scale; ECOG, Eastern Cooperative Oncology Group Performance Status; VCF, vertebral compression fracture.

Table 2

Group B (B-literature): assesses the effect of either surgery or radiotherapy in SINS 7–12 patients, perhaps as a sub-group analysis

Study	Study design	Study population (only patients with SINS 7–12)	Exposure (initial treatment)	Outcomes measured	Potential confounders assessed	Results
Pennington et al. [31] (2019)	Retrospective cohort study	38 neurological intact patients	Consulted for metastatic spinal disease	Probability of undergoing stabilization surgery	rTokuhashi score, ESCC scale, baseline neurologic status, oncologic status, and age	2 patients (11%) with a SINS of 7–9 were treated with instrumented fusion, compared with 15 patients (79%) with a SINS of 10–12 (p<0.01).
Kim et al. [28] (2020)	Retrospective cohort study	47 neurologically intact patients	Initially conservative treatment	Conversion to surgery	Sex, age, primary cancer, Tomita score, rTokuhashi score, performance status, SINS components, Bilsky grade, radio sensitivity of tumor	33% of patients converted to surgery in the first year. The need for conversion to surgery increased statistically significantly when vertebral body collapse was less than 50% (p=0.039) or the tumor was in the semi-rigid region (T3–T10) (p=0.042)
Hussain et al. [32] (2019)	Prospective cohort study	93 patients	Stabilization surgery	PRO on pain and activity/disability	Age, sex, primary tumor, surgical stabilization technique, ESCC scale, SINS components, treatment level, postoperative treatment, ASIA score	For patients with SINS 7–9 stabilization did not result in statistically significant decreases in PRO for average pain (–0.95; p=0.18) or disability (0.24; p=0.89) For patients with SINS 10–12 stabilization resulted in significant decreases in PRO for average pain (–2.2; p<0.0001) and disability (–2.0; p=0.0006)
Masuda et al. [34] (2018)	Retrospective cohort study	24 patients	Decompression and stabilization surgery	Frankel score; Performance score	Performance score, Frankel score, sex, age, follow-up period, Tokuhashi score, Katagiri score	Frankel score significantly improved from 2.8 to 3.6 (p<0.001) Performance status significantly improved from 3.2 to 2.1 (p<0.001)
Wänman et al. [25] (2021)	Retrospective cohort study	70 patients with prostate cancer who underwent surgery for MSCC	Surgery	Ability to ambulate	aOR for Hormone-status, SINS, performance status, ambulation before surgery	Ability to walk was significantly improved after surgery (p<0.001) No statistically significant difference in the overall risk for death (aOR, 1.3; p=0.4) between the SINS potentially unstable and unstable categories and risk of loss of ambulation 1 month after surgery (aOR, 1.4; p=0.6)
Dakson et al. [30] (2020)	Retrospective cohort study	43 patients	Radiotherapy	Change in SINS-group	Age, sex, primary tumor, patient prognosis, Frankel score, treatment modalities, performance status	1 patient (2.3%) changed status to stable, 29 patients (67.4%) remained potentially unstable, and 13 patients (30.2%) changed status to unstable. A significant proportion of patients with potentially unstable SINS (30%) progressed into unstable SINS category at an average 364 days (p<0.001)
Gallizia et al. [37] (2017)	Prospective cohort study	69 patients	3D conformal radiotherapy	Change in SINS-group; Pain	Sex, gender, primary tumor, location of spinal metastases, other metastases, performance status	17 potentially unstable patients (27.4%) became stable. 7 potentially unstable patients (10%) had worsening pain at rest and 20% had worsened breakthrough pain while 50% had decreased pain at rest and 60% had decreased breakthrough pain
Sahgal et al. [42] (2013)	Prospective cohort study	209 patients	SBRT	Development of VCF	Primary tumor, spine level, paraspinal/epidural disease, systemic therapy, bisphosphonate therapy, age, radiation dose and fractions, follow-up time, local progression, prior radiation, SINS characteristics	42 patients (20.1%) developed VCF
Lee et al. [38] (2016)	Retrospective cohort study	38 patients with low degree cord compression or cauda equina	SBRT	Development of symptomatic VCF	Age, sex, primary tumor, overall SINS, Bilsky classification, lesion level, radiation dose and fractions, systemic therapy last 2 months, prior radiation	12 patients (31.6%) developed symptomatic VCF
Huisman et al. [41] (2014)	Retrospective case-control study	26 cases retreated after initial radiotherapy matched to 40 controls	Radiotherapy	Radiotherapy failure (revision treatment)	aOR for sex, performance score, primary tumor, and symptoms	SINS score 7–12 is significantly associated with radiotherapy failure: OR, 5.9 (95% CI, 1.1–31.7); p=0.04
Te Velde et al. [21] (2024)	Retrospective multicenter cohort study	127 patients who underwent cEBRT due to spinal myoloma	cEBRT	VCF	Age, sex, BMI, follow-uptime, ACCI, ECOG, NRS, and more	Total and categorial SINS score is associated with the risk of developing VCF.
McKibben et al. [22] (2023)	Retrospective cohort study	170	Radiation	Radiation therapy failure (persistent pain, need for reradiation, or surgical intervention	Primary tumor origin, sensitivity to radiation, age, gender, Karnofsky and ECOG score, Tomita score, time between diagnosis and initiation of treatment, radiation technique, and dose	No statistic significant association between SINS score and radiation failure were found.
Kim et al. [23] (2023)	Retrospective cohort study	84	SABR	VCF	Age, sex, BMI, Preexisting VCF, BED	Cumulative incidence of VCF at 12 months with SINS 7–12=26% (p<0.001)
Vargas et al. [26] (2021)	Retrospective cohort	75 patients with tumor related SINS score 7–12 with non-operative approach at first.	Non operative approach	Surgery within a year after nonoperative approach	Age, BED, whether the patient had surgical intervention.	34.7% underwent surgery within a year. Higher patient count with SINS 12 in surgery group 55.2% compared to no surgery 44.8% (p=0.003) Optimal cut off value of SINS is >10 resulting in higher risk of requiring surgical intervention.
Lenschow et al. [24] (2022)	Retrospective	331 patients with SINS 7–12 where included.	Instrumentation vs. radiotherapy (9%), decompression without instrumentation (13%), vertebral augmentation (2%)	Neurological outcomes, using Frankel score	Age, gender, KPS, comorbidities, smoking, arteriosclerosis, diabetes, obesity, thrombosis, osteoporosis, and more	76.1% underwent spinal instrumentation. Neurological outcomes between instrumentation and non-instrumentation were not significantly different (p=0.612). More frequent instrumentation in the SINS 10–12 group compared to SINS 7–9. No difference in neurological outcomes in the individual subgroups SINS 7–9 and SINS 10–12. Complication occurred more frequently in the surgical group compared to no surgery.
Lam et al. [39] (2015)	Retrospective	173	Palliative radiotherapy	Risk for spinal adverse events	Age, gender, BMI, ECOG performance status, and more	SINS ≥10: HR, 1.68; p=0.09 SINS ≥11: HR, 2.57; p=0.004 SINS ≥12: HR, 2.79; p=0.0012 SINS ≥11 vs. <11: HR, 2.52; p=0.007
Shi et al. [33] (2018)	Retrospective	137	Conventional radiotherapy	New or worsened fracture	Sex, age, ECOG, histology, and dose	SINS 7–12: HR, 1.66; 95% CI, 0.85–3.22; p=0.14 SINS 7–9: HR, 1.58; p=0.55 SINS 10–12: HR, 2.80; p=0.17 Conclusion: Among potentially unstable (SINS 7–12) lesions, SINS alone was less predictive of subsequent new or worsening fracture.
Sullivan et al. [27] (2020)	Retrospective	98	Radiotherapy	Mean survival after treatment	Sex, age, specific cancers, posterior instrumentation, and more	Mean survival after treatment were 15 months (5 days–102 months)
Donnellan et al. [29] (2020)	Retrospective	68	Surgery (vertebrectomy)	LOS, minor and major complication, ICU stay	Age, LOS, operative time, survival	There was a significant difference (p<0.001) in survival days after between the indeterminate group (435 days) and the unstable group (126 days). The majority of patients (n=119) had a favorable Frankel grade after procedure. There were no differences in the operative time, inpatient hospital length of stay, complications, or need for ICU between SINS 7–12 and SINS 13–18 There was a significant difference (p=0.006) for intraoperative blood loss between the indeterminate group (1,400 mL) and the unstable group (850 mL).
Zadnik et al. [40] (2014)	Retrospective	10	Surgery; 70% also had radiotherapy.	Length of survival	Location of tumor, postoperative adjuvant therapy	Length of survival in SINS 7–12 were 28.9 months.
Chang et al. [36] (2018)	Retrospective	44	Surgery; some also underwent radiotherapy. Not specified.	Spinal adverse event	Factors with a p-value of <0.10 in the univariate analysis were used for multivariate analysis	HR for VCF Crude HR (univariate analysis), 3.93; 95% CI, 1.10–14.03 Adjusted HR (multivariate analysis), 0.577; 95% CI, 0.09–3.72; not significant. Spinal cord compression No association between SINS 7–12 and spinal cord compression.
Hussain et al. [35] (2018)	Prospective	93	Surgery; 66 underwent post-surgery radiotherapy.	PRO		Stabilization significantly improved nearly all PRO measures for patients with indeterminate SINS Increasing SINS and categorial SINS correlated with severity of preoperative disability with BPI walking (rho=0.19; p=0.04), MDASI activity (rho=0.24; p=0.006), and MDASI walking (rho=0.20; p=0.03)
Al-Omair A. et al. [43] (2012)	Retrospective	72	SBRT	VCF	Used a multivariate analysis	19% treated with SBRT got VCF in SINS 7–12

SINS, spinal instability neoplastic score; ESCC, epidural spinal cord compression; PRO, patient-reported outcome; ASIA, American Spinal Injury Association; MSCC, metastatic spinal cord compression; aOR, adjusted odds ratio; SBRT, stereotactic body radiation therapy; VCF, vertebral compression fracture; OR, odds ratio; CI, confidence interval; cEBRT, conventional external beam radiation therapy; BMI, body mass index; ACCI, age-adjusted Charlson Comorbidity Index; ECOG, Eastern Cooperative Oncology Group Performance Status; NRS, Numeric Rating Scale; SABR, stereotactic ablative body radiotherapy; BED, biologically effective dose; KPS, Karnofsky Performance Scale; HR, hazard ratio; LOS, length of survival; ICU, intensive care unit; MDASI, MD Anderson Symptom Inventory.

Table 3

Quality assessment of the included studies by use of the EPHPP tool

Study, Country	Selection bias	Study design	Confounders	Blinding	Data collection	Withdrawals and drop-outs	Global rating^a)
Dial et al. [19] (2020), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Versteeg et al. [14] (2021), The Netherlands	Moderate	Moderate	Strong	Moderate	Moderate	Moderate	Strong
Vargas et al. [20] (2023), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Pennington et al. [31] (2019), USA	Strong	Moderate	Weak	Moderate	Strong	Strong	Moderate
Kim et al. [28] (2020), Korea	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Hussain et al. [32] (2019), USA	Moderate	Moderate	Weak	Moderate	Strong	Moderate	Moderate
Masuda et al. [34] (2018), Japan	Moderate	Moderate	Strong	Moderate	Moderate	Weak	Moderate
Wänman et al. [25] (2021), Sweden	Weak	Moderate	Moderate	Moderate	Strong	Strong	Moderate
Dakson et al. [30] (2020), Canada	Moderate	Moderate	Strong	Moderate	Strong	Weak	Moderate
Gallizia et al. [37] (2017), Italy	Moderate	Moderate	Weak	Moderate	Strong	Strong	Moderate
Sahgal et al. [42] (2013), Canada	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Lee et al. [38] (2016), USA	Weak	Moderate	Strong	Moderate	Strong	Strong	Moderate
Huisman et al. [41] (2014), The Netherlands	Moderate	Moderate	Strong	Moderate	Strong	Not applicable	Strong
Te Velde et al. [21] (2024), USA	Weak	Moderate	Strong	Moderate	Strong	Moderate	Moderate
McKibben et al. [22] (2023), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Kim et al. [23] (2023), Korea	Weak	Moderate	Strong	Moderate	Strong	Strong	Strong
Vargas et al. [26] (2021), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Lenschow et al. [24] (2022), Germany	Moderate	Moderate	Strong	Moderate	Moderate	Strong	Strong
Lam et al. [39] (2015), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Shi et al. [33] (2018), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Sullivan et al. [27] (2020), USA	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Donnellan et al. [29] (2020), Australia	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Zadnik et al. [40] (2014), USA	Weak	Moderate	Strong	Moderate	Strong	Strong	Moderate
Chang et al. [36] (2018), Korea	Moderate	Moderate	Strong	Moderate	Strong	Strong	Strong
Hussain et al. [35] (2018), USA	Moderate	Moderate	Weak	Moderate	Strong	Strong	Moderate
Al-Omair et al. [43] (2012), Canada	Moderate	Moderate	Weak	Moderate	Strong	Strong	Moderate

EPHPP, Effective Public Health Practice Project.

^a) Global rating: <1 weak: strong, 1 weak: moderate, >1 weak: weak.

References

1. Van den Brande R, Cornips EM, Peeters M, Ost P, Billiet C, Van de Kelft E. Epidemiology of spinal metastases, metastatic epidural spinal cord compression and pathologic vertebral compression fractures in patients with solid tumors: a systematic review. J Bone Oncol 2022;35:100446.

2. Wanman J, Grabowski P, Nystrom H, et al. Metastatic spinal cord compression as the first sign of malignancy. Acta Orthop 2017;88:457–62.

3. Wewel JT, O’Toole JE. Epidemiology of spinal cord and column tumors. Neurooncol Pract 2020;7(Suppl 1): i5–9.

4. Wang M, Bunger CE, Li H, et al. Improved patient selection by stratified surgical intervention: Aarhus spinal metastases algorithm. Spine J 2015;15:1554–62.

5. Morgen SS, Engelholm SA, Larsen CF, Sogaard R, Dahl B. Health-related quality of life in patients with metastatic spinal cord compression. Orthop Surg 2016;8:309–15.

6. Nater A, Sahgal A, Fehlings M. Management: spinal metastases. Handb Clin Neurol 2018;149:239–55.

7. Mossa-Basha M, Gerszten PC, Myrehaug S, et al. Spinal metastasis: diagnosis, management and follow-up. Br J Radiol 2019;92:20190211.

8. Boussios S, Cooke D, Hayward C, et al. Metastatic spinal cord compression: unraveling the diagnostic and therapeutic challenges. Anticancer Res 2018;38:4987–97.

9. Zhang HR, Li JK, Yang XG, Qiao RQ, Hu YC. Conventional radiotherapy and stereotactic radiosurgery in the management of metastatic spine disease. Technol Cancer Res Treat 2020;19:1533033820945798.

10. Barzilai O, Fisher CG, Bilsky MH. State of the art treatment of spinal metastatic disease. Neurosurgery 2018;82:757–69.

11. Fisher CG, DiPaola CP, Ryken TC, et al. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine (Phila Pa 1976) 2010;35:E1221–9.

12. Murtaza H, Sullivan CW. Classifications in brief: the spinal instability neoplastic score. Clin Orthop Relat Res 2019;477:2798–803.

13. Hong SH, Chang BS, Kim H, Kang DH, Chang SY. An updated review on the treatment strategy for spinal metastasis from the spine surgeon’s perspective. Asian Spine J 2022;16:799–811.

14. Versteeg AL, Sahgal A, Rhines LD, et al. Health related quality of life outcomes following surgery and/or radiation for patients with potentially unstable spinal metastases. Spine J 2021;21:492–9.

15. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.

16. Ciliska D, Miccouci S, Dobbins M. Effective Public Health Practice Project. Quality assessment tool for quantitative studies [Internet] Hamilton (ON): Effective Public Health Practice Project. 1998 [cited 2025 Feb 5]. Available from: https://merst.healthsci.mcmaster.ca/wp-content/uploads/2022/08/quality-assessment-tool_2010.pdf

17. Ciliska D, Miccouci S, Dobbins M. Effective Public Health Practice Project. Quality assessment tool for quantitative studies: dictionary [Internet] Hamilton (ON): Effective Public Health Practice Project. 1998 [cited 2025 Feb 5]. Available from: https://merst.healthsci.mcmaster.ca/wp-content/uploads/2022/08/qualilty-assessment-dictionary_2010bb4cc44d23b4446e95ef53f3430f51c6.pdf

18. Catanzano A, Dial B, Alamin TF, et al. P49. Treatment preferences for patients with metastatic spine disease with indeterminate spinal instability neoplastic scores (SINS 7–12). Spine J 2019;19:S181.

19. Dial BL, Catanzano AA, Esposito V, et al. Treatment outcomes in spinal metastatic disease with indeterminate stability. Global Spine J 2022;12:373–80.

20. Vargas E, Shabani S, Mummaneni PV, et al. Does surgery for metastatic spinal tumors improve functional outcomes in patients without spinal cord compression but with potentially unstable spines (SINS 7–12)? J Neurosurg Spine 2023;39:287–94.

21. Te Velde JP, Zijlstra H, Lans A, et al. Fracture rate after conventional external beam radiation therapy to the spine in multiple myeloma patients. Spine J 2024;24:137–45.

22. McKibben NS, MacConnell AE, Chen Y, et al. Risk factors for radiotherapy failure in the treatment of spinal metastases. Global Spine J 2025;15:831–7.

23. Kim TH, Kim J, Lee J, Nam TK, Choi YM, Seong J. Vertebral compression fracture after stereotactic ablative radiotherapy in patients with oligometastatic bone lesions from hepatocellular carcinoma. Clin Transl Radiat Oncol 2023;41:100636.

24. Lenschow M, Lenz M, von Spreckelsen N, et al. Impact of spinal instrumentation on neurological outcome in patients with intermediate Spinal Instability Neoplastic Score (SINS). Cancers (Basel) 2022;14:2193.

25. Wanman J, Jernberg J, Gustafsson P, et al. Predictive value of the spinal instability neoplastic score for survival and ambulatory function after surgery for metastatic spinal cord compression in 110 patients with prostate cancer. Spine (Phila Pa 1976) 2021;46:550–8.

26. Vargas E, Lockney DT, Mummaneni PV, et al. An analysis of tumor-related potential spinal column instability (Spine Instability Neoplastic Scores 7–12) eventually requiring surgery with a 1-year follow-up. Neurosurg Focus 2021;50:E6.

27. Sullivan PZ, Albayar A, Ramayya AG, et al. Association of spinal instability due to metastatic disease with increased mortality and a proposed clinical pathway for treatment. J Neurosurg Spine 2020;32:950–7.

28. Kim YH, Kim J, Chang SY, Kim H, Chang BS. Treatment strategy for impending instability in spinal metastases. Clin Orthop Surg 2020;12:337–42.

29. Donnellan CJ, Roser S, Maharaj MM, Davies BN, Ferch R, Hansen MA. Outcomes for vertebrectomy for malignancy and correlation to the Spine Instability Neoplastic Score (SINS): a 10-year single-center perspective. World Neurosurg 2020;138:e151–9.

30. Dakson A, Leck E, Brandman DM, Christie SD. The clinical utility of the Spinal Instability Neoplastic Score (SINS) system in spinal epidural metastases: a retrospective study. Spinal Cord 2020;58:892–9.

31. Pennington Z, Ahmed AK, Westbroek EM, et al. SINS score and stability: evaluating the need for stabilization within the uncertain category. World Neurosurg 2019;128:e1034–47.

32. Hussain I, Barzilai O, Reiner AS, et al. Spinal Instability Neoplastic Score component validation using patient-reported outcomes. J Neurosurg Spine 2019;30:432–8.

33. Shi DD, Hertan LM, Lam TC, et al. Assessing the utility of the spinal instability neoplastic score (SINS) to predict fracture after conventional radiation therapy (RT) for spinal metastases. Pract Radiat Oncol 2018;8:e285–94.

34. Masuda K, Ebata K, Yasuhara Y, Enomoto A, Saito T. Outcomes and prognosis of neurological decompression and stabilization for spinal metastasis: is assessment with the spinal instability neoplastic score useful for predicting surgical results? Asian Spine J 2018;12:846–53.

35. Hussain I, Barzilai O, Reiner AS, et al. Patient-reported outcomes after surgical stabilization of spinal tumors: symptom-based validation of the Spinal Instability Neoplastic Score (SINS) and surgery. Spine J 2018;18:261–7.

36. Chang SY, Ha JH, Seo SG, Chang BS, Lee CK, Kim H. Prognosis of single spinal metastatic tumors: predictive value of the spinal instability neoplastic score system for spinal adverse events. Asian Spine J 2018;12:919–26.

37. Gallizia E, Apicella G, Cena T, Di Genesio Pagliuca M, Deantonio L, Krengli M. The spine instability neoplastic score (SINS) in the assessment of response to radiotherapy for bone metastases. Clin Transl Oncol 2017;19:1382–7.

38. Lee SH, Tatsui CE, Ghia AJ, et al. Can the spinal instability neoplastic score prior to spinal radiosurgery predict compression fractures following stereotactic spinal radiosurgery for metastatic spinal tumor?: a post hoc analysis of prospective phase II single-institution trials. J Neurooncol 2016;126:509–17.

39. Lam TC, Uno H, Krishnan M, et al. Adverse outcomes after palliative radiation therapy for uncomplicated spine metastases: role of spinal instability and single-fraction radiation therapy. Int J Radiat Oncol Biol Phys 2015;93:373–81.

40. Zadnik PL, Hwang L, Ju DG, et al. Prolonged survival following aggressive treatment for metastatic breast cancer in the spine. Clin Exp Metastasis 2014;31:47–55.

41. Huisman M, van der Velden JM, van Vulpen M, et al. Spinal instability as defined by the spinal instability neoplastic score is associated with radiotherapy failure in metastatic spinal disease. Spine J 2014;14:2835–40.

42. Sahgal A, Atenafu EG, Chao S, et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. J Clin Oncol 2013;31:3426–31.

43. Al-Omair A, da Cunha M, Atenafu E, et al. The risk of Vertebral Compression Fracture (VCF) postspine Stereotactic Body Radiation Therapy (SBRT) and evaluation of the Spinal Instability Neoplastic Score (SINS). Int J Radiat Oncol Biol Phys 2012;84:S39–40.

44. Versteeg AL, van der Velden JM, Verkooijen HM, et al. The effect of introducing the spinal instability neoplastic score in routine clinical practice for patients with spinal metastases. Oncologist 2016;21:95–101.

45. Kim YR, Lee CH, Yang SH, et al. Accuracy and precision of the spinal instability neoplastic score (SINS) for predicting vertebral compression fractures after radiotherapy in spinal metastases: a meta-analysis. Sci Rep 2021;11:5553.

46. Costa MC, Eltes P, Lazary A, Varga PP, Viceconti M, Dall’Ara E. Biomechanical assessment of vertebrae with lytic metastases with subject-specific finite element models. J Mech Behav Biomed Mater 2019;98:268–90.

47. Costa MC, Campello LB, Ryan M, Rochester J, Viceconti M, Dall’Ara E. Effect of size and location of simulated lytic lesions on the structural properties of human vertebral bodies, a micro-finite element study. Bone Rep 2020;12:100257.

48. Bijur PE, Silver W, Gallagher EJ. Reliability of the visual analog scale for measurement of acute pain. Acad Emerg Med 2001;8:1153–7.

49. Ivanishvili Z, Fourney DR. Incorporating the spine instability neoplastic score into a treatment strategy for spinal metastasis: LMNOP. Global Spine J 2014;4:129–36.

50. Laufer I, Rubin DG, Lis E, et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist 2013;18:744–51.

51. Kwan WC, Zuckerman SL, Fisher CG, et al. What is the optimal management of metastatic spine patients with intermediate spinal instability neoplastic scores: to operate or not to operate? Global Spine J 2025;15(1_suppl): 132S–142S.