Cancer incidence rates are expected to increase; however, cancer-related deaths are expected to decrease due to improved systemic therapy.1 As a result, the incidence of patients with spinal metastases will increase as will the complexity of management. Spinal metastases can be devastating with the development of spinal instability, which can cause neurological injury and severe pain. Therefore, early recognition of spinal instability is increasingly important and a concept that has previously been under-recognized within oncology. The diagnosis of instability is challenging and both clinical signs and symptoms, and radiological findings must be considered.
Criteria used to define and diagnose neoplastic-related spinal instability should be unambiguous and easily assessable for physicians taking care of this patient population to prevent interobserver variability. A previous systematic review by Weber et al2 demonstrated the controversy about the definition, diagnosis, and assessment of spinal neoplastic-related instability. In response, the spinal oncology study group (SOSG) defined spinal neoplastic-related instability as “loss of spinal integrity as a result of a neoplastic process that is associated with movement-related pain, symptomatic or progressive deformity, and/or neural compromise under physiologic loads.”3 Subsequently, the Spinal Instability Neoplastic Score (SINS) was developed to assess the degree of spinal (in)stability in a standardized way.3 The aims of SINS were to improve communication and referrals among medical specialists involved in the treatment of spinal metastases.3 Furthermore, SINS could enhance the uniform reporting of spinal neoplastic-related instability in scientific studies.3 Therefore, the objective of this study was to determine the impact of SINS, since its introduction by publication in 2010, on clinical decision-making and outcome reporting in patients with spinal metastases.
The following questions were addressed in this systematic literature review:
- How is spinal neoplastic instability defined or classified in the literature before and after introduction of SINS?
- How has SINS affected daily clinical practice?
- Can SINS be used as a prognostic tool?
MATERIALS AND METHODS
This systematic literature review is conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.4 An electronic search was conducted in December 2015 using the PubMed, Embase, Clinicaltrials.gov, National Institutes of Health, and controlled clinical trials databases. The search strategy was adopted to fit the specific database. The following search terms, synonyms, and related key words, were combined using Boolean operators: “spinal neoplasms” [Mesh], “Neoplasm metastasis” [Mesh], “spine” [Mesh], “vertebral column” [Title/Abstract], “unstable” [Title/Abstract], “spinal instability” [Title/Abstract], and “spinal instability neoplastic score” [Title/Abstract]. The search strategy was designed to secure a broad range of articles concerning neoplastic-related spinal instability. Inclusion of articles was limited to English publications. Duplicates were removed.
Studies concerning the definition or classification of spinal neoplastic-related instability were eligible for inclusion. Titles and abstracts were screened for relevance using prespecified in- and exclusion criteria. Full-text papers were screened and assessed for eligibility according to the selection criteria described in Supplemental Digital Content, Table 1, http://links.lww.com/BRS/B213. Studies without a radiographic or clinical description, definition, or classification of spinal instability were excluded. References of included articles were hand-searched to identify additional articles.
Data extraction was performed by one reviewer (ALV) using a prespecified form relevant to the related question. The primary outcomes for the study questions were:
- Any definition and/or radiographic criteria and/or classification of spinal (in)stability in vertebrae with metastases.
- Any study describing the use of SINS.
- SINS as prognostic factor.
Considering the descriptive nature of this review and the wide range of study designs, quality of evidence was only assessed for studies related to the third research question and was assessed by a single reviewer (ALV) using prespecified criteria, including the description of the research question, methodology, study population, data collection, and reporting of results. Quality of evidence was rated as high, moderate, low, or very low according to the GRADE system.5
Figure 1 outlines the literature search and selection process. The electronic search yielded 1414 unique articles after removal of 619 duplicates. Most articles were excluded during title and abstract screening because of failure to describe patients with neoplastic-related instability. A total of 51 articles and 18 (ongoing) trials met the inclusion criteria.
Radiographic and Clinical Definitions of Stability
The majority of papers describing spinal instability due to spinal metastases used a clinical definition or report-specific radiographic criteria. A total of 11 papers used the presence of mechanical back pain, defined as pain aggravated by movement and relieved by recumbency, as the critical symptom for the presence of spinal instability.6–16
In addition to mechanical back pain, several authors described radiographic signs for spinal neoplastic-related instability. Radiographic signs that may be considered evidence of spinal instability include; >40% tumor involvement of the vertebral body,10 presence of 50% or more vertebral body collapse,10,16 presence of kyphotic deformity,17 progressive deformity,15 subluxation,15,17 translation,15 or a retro-pulsed bone fragment in the spinal canal.17
(In)stability Classifications Before Development of SINS
Historically, biomechanical criteria developed for traumatic fractures were applied to assess spinal instability in patients with spinal metastases.18 In an attempt to develop specific criteria for spinal neoplastic-related instability, Kostuik and Errico modified the three-column system of Denis19 into a six-column system by dividing the columns in the sagittal plane.18,20,21 Involvement of three or four columns is deemed as “impending unstable” and involvement of five or six columns as “unstable.”21
The retrospective study by Asdourian et al22 reported the pathogenesis of spinal deformity due to vertebral metastases in a cohort using radiographic imaging. A consistent pattern of vertebral failure was observed and a classification system was developed to describe the different stages of vertebral failure.22
Siegal et al proposed the following criteria for spinal instability in patients with spinal metastases; (A) anterior and middle column involvement or >50% collapse of vertebral body height, (B) middle and posterior column involvement or shearing deformity, (C) three column involvement, (D) involvement of the same column in two or more adjacent vertebrae, or (E) iatrogenic instability: laminectomy, resection of >50% of the surface of the vertebral body.23,24
Following these reports, Taneichi et al25 investigated the association between the occurrence of vertebral body collapse and the size and location of a lytic lesion to determine a critical defect size. A score for the lumbar and thoracic vertebrae was developed to determine the risk of vertebral body collapse.25 However, none of these classification systems has been validated.
In response to the controversy about the definition and assessment of spinal neoplastic-related instability, the SOSG defined spinal neoplastic-related instability and simultaneously developed the SINS score as a tool to assess spinal instability. SINS consists of five radiographic and one clinical parameters (Supplemental Digital Content, Table 2, http://links.lww.com/BRS/B213).3 The sum of these parameters results in a total score between zero and 18. Zero to six points denote spinal stability, seven to 12 denote impending spinal instability, and a score above 12 denotes spinal instability.3 Consultation of a spine surgeon is recommended for scores of seven and above.3 Of note, SINS was not developed as a treatment guide, but merely as a classification tool to assess spinal (in)stability and to improve communication and referrals between medical specialists.3
Reliability and predictive validity was first tested among the members of the SOSG, including 30 international spine oncology experts primarily from neurosurgical and orthopaedic specialties.26 Validity of SINS was tested comparing the consensus opinion regarding stability (gold standard) to a binary SINS score of stability (stable vs. (impending) unstable).26 A sensitivity and specificity for the binary SINS score of 95.7% and 79.5%, respectively, was demonstrated. Near-perfect intra- and interobserver reliability could be determined for the total SINS score.26
In view of the multidisciplinary aspect of care of patients with spinal metastases, the AOSpine Knowledge Forum Tumor (AOSKFT) also tested the reliability of SINS among an international panel of radiation oncologists and radiologists. Substantial interobserver and excellent intraobserver reproducibility to distinguish between stable and (impending) unstable lesions was demonstrated.27,28
Besides the reliability studies of the AOSKFT, reliability of SINS was also tested in three independently conducted studies.29–31 The studies of Teixeira et al and Campos et al demonstrated fair to excellent interobserver reliability for the total SINS score.29,30 Clinical experience with spinal metastases demonstrated to increase reliability.30 The observers in these studies mainly consisted of spinal surgeons. Arana et al31 used 83 medical specialists, including neurosurgeons, medical oncologists, radiation oncologists, radiologists, and orthopaedic surgeons to rate SINS on 90 cases. Excellent intraobserver and moderate interobserver reliability was found for the total SINS score.31
SINS in Clinical Practice
After publication of the SINS classification, numerous studies used SINS to classify the degree of spinal (in)stability in patients who underwent surgery or radiotherapy for spinal metastases.32–39 However, Rief et al used the Taneichi classification to assess spinal instability.40,41
Moreover, the definition of spinal instability and the SINS score have been adopted in several clinical practice guidelines and decision frameworks for patients with spinal metastases. The NOMS criteria are a clinical decision framework for patients with spinal metastases; including four critical assessments: neurologic (N), oncologic (O), mechanical stability (M), and systemic disease (S).14 Assessment of the mechanical component consisted of the presence or absence of mechanical pain before the development of SINS.12,13,42 After publication, SINS was incorporated in the NOMS criteria as classification to assess mechanical instability.14 Ivanishvili and Fourney43 advocated their own decision framework called LMNOP. The LMNOP framework considers location of the disease (L), mechanical instability as assessed by SINS (M), neurologic status (N), oncological history (O), and the physical status of the patient (P).43 Furthermore, the American College of Radiology (ACR) has incorporated SINS in their practice guideline for metastatic spinal cord compression and recurrent metastatic disease.44 The American Academy of Orthopedic Surgeons (AAOS) incorporated SINS as classification for spinal instability in an instructional lecture on the management of patients with bone metastases for general practitioners.45
With SINS increasingly being implemented in clinical guidelines, Versteeg et al46 sought to determine the influence of implementing SINS in clinical practice. A decrease in SINS scores was found in both a surgical and radiotherapy cohort after introduction of SINS. This effect was explained by increased awareness of spinal (in)stability in patients with spinal metastases and subsequent earlier referral to a spinal surgeon.46
Prognostic Value of SINS
A total of 12 studies investigated the prognostic value of SINS, quality of evidence of the articles was rated as low to very low. Huisman et al47 investigated the relationship between the degree of spinal instability, as reflected by the SINS score, and the need for reirradiation. The risk on the need for retreatment increased with an increasing SINS score (HR 1.3, 95% CI 1.1–1.5).47 Lam et al48 studied the relationship between the SINS score and occurrence of Spinal Adverse Events (SAE) after palliative radiotherapy. Multivariate analysis revealed an increased risk on SAE with a SINS score of 11 or above (HR 2.5, 95% CI 1.3–4.9).48
Three studies investigated the prognostic value of SINS for survival after surgical treatment. All three studies demonstrated no prognostic value of SINS for postoperative survival.34,35,49
The majority of studies investigated the predictive value of SINS and/or components of SINS for the occurrence of vertebral compression fracture (VCF) after stereotactic body radiotherapy (SBRT).50–56 Factors that were independently associated with post-SBRT occurrence of VCF included: the presence of vertebral body collapse at baseline, the presence of a lytic lesion, malalignment of the spine, higher overall SINS score, and non-SINS-related factors including a higher dose per fraction and single fraction SBRT50–54 (Supplemental Digital Content, Table 3, http://links.lww.com/BRS/B213). In contrast, two other studies demonstrated no relationship between SINS or SINS components and the occurrence of VCF post-SBRT.55,56
Spinal Stability in (Ongoing) Trials
A total of 18 registered clinical trials were retrieved that included spinal stability in their research protocol, either as in- or exclusion criteria, or as an outcome parameter.57–74 Four of these trials incorporated SINS as a parameter for stability.58,60,62,72
The SINS classification was published in 2010 in response to the controversy that existed regarding the definition and assessment of spinal neoplastic-related instability.3 Originally, SINS was developed as a classification to assess the degree of spinal instability and to improve communication among the different medical specialists involved with the care of patients with spinal metastases.3 More than 5 years later we sought to investigate the effect of the introduction of SINS on the literature concerning spinal neoplastic-related instability. A lack of consensus existed regarding the definition, assessment, and reporting about spinal neoplastic-related instability before publication of SINS. After the introduction of SINS, almost all published studies concerning spinal instability used SINS to classify the degree of spinal neoplastic-related instability.32–39 Furthermore, several studies sought to investigate if spinal instability, as reflected by SINS, has a prognostic value for patients who undergo surgical or radiotherapy treatment.34,35,47–56 It should be noted that the SINS score is the sum of individual components of which some quantify the risk of spinal instability (e.g., location, lesion quality) while other factors express the current degree of spinal instability (e.g., the presence of mechanical pain, deformity). SINS may, therefore, not be the optimal tool to assess the prognostic value of spinal neoplastic-related instability. Furthermore, mechanical stability is only one component that influences clinical decision-making and treatment outcome. Future studies should, therefore, focus on the impact of the individual components of SINS on treatment outcome, as was demonstrated in earlier published studies,51 combined with other known prognostic factors such as performance status.75
The total SINS score or individual components of SINS demonstrated to have a prognostic value for radiotherapy failure and the occurrence of VCF post-SBRT. However, these studies were limited by a lack of unstable cases (SINS >12) and a non-normal distribution of the SINS score. The prognostic value of SINS was investigated mainly in studies concerning patients who were treated with radiotherapy. The lack of unstable cases can be explained by the use of the SINS score in clinical practice as demonstrated by the study by Versteeg et al,46 which showed a decrease in SINS scores in both the radiotherapy and surgical cohort after introduction of SINS. This phenomenon is thought to occur due to increased awareness of spinal instability when using SINS and subsequent earlier referral to a spinal surgeon, as spinal instability is a (relative) indication for surgical intervention.46 These results support the use of SINS as a valuable tool in daily clinical practice to facilitate timely referral. It should, however, be noted that SINS is not (prospectively) validated due to the lack of a gold standard and moreover as a wait-and-see policy to assess progression of instability is unethical. The prognostic value of SINS for progression of instability is therefore unknown.
Consultation of a spine surgeon is recommended for SINS scores above 7, reflecting impending spinal instability (7–12) or spinal instability (>12).3 However, due to the construction of the SINS score, including components that quantify both the degree of instability and the risk of instability, a score of 9 may identify a patient with impending instability, but could also reflect an unstable situation. In its current form, the total SINS score is calculated by the sum of each category. This approach ignores the fact that some combinations of components are more unstable than others which might be overcome by multiplication of certain categories if they coexist instead of the sum of the individual components.
The increasing incidence of spinal metastases has led to an increased need for surgical and radiotherapy interventions to maintain or improve patient-related quality of life. To develop evidence-based treatment strategies for spinal neoplastic-related instability, it is important to use uniform definitions and outcome parameters. Consistent use of SINS and/or the components of SINS to study spinal instability will facilitate uniform reporting of results and could ultimately enhance the quality of the research and patient outcomes.
Several investigators have used finite element modeling to investigate risk factors for pathologic vertebral fracture and to develop a CT-scan-based model to assess the present risk.2 However, none of these studies has led to the development of an instrument for clinical practice. Snyder et al76 used CTRA as a noninvasive method to predict vertebral fracture in breast cancer patients with spinal metastases. However, clinical implementation is limited due to the requirement of advanced operator input to create bone models for evaluation.76 In addition, the time required for analysis is lengthy.76 Furthermore, the CTRA's application in the spine is questionable given that not all vertebral fractures are symptomatic or suggest instability. In contrast, spinal (in)stability as classified by SINS is based on six common radiographic and clinical parameters and does not need sophisticated analyzing methods. Moreover, the results of Versteeg et al46 seem to support the clinical usefulness as a referral tool. It should, however, be noted that the final judgment of current or prospective (in)stability still depends on the experience of the spinal surgeon. Future studies working toward a practical and reliable simulation model based on individualized CT-data could, therefore, still be beneficial for daily clinical practice.
SINS was originally developed as a classification tool to assess spinal (in)stability in response to the existing controversy surrounding spinal neoplastic-related instability. Aims of the SINS were to improve communication and referrals among different medical specialists. The SINS consists of components quantifying the risk and the current degree of spinal instability and therefore, may not be appropriate to use as a prognostic tool. However, the SINS components vertebral body collapse, lytic lesion, and malalignment of the spine demonstrated to be associated with post-SBRT VCF.50–54
After its introduction, SINS has been widely used to classify the degree of spinal instability. Moreover, SINS has been incorporated in multiple treatment guidelines, resulting in more uniform reporting and defining of spinal neoplastic-related instability, and earlier referral of patients with (impending) unstable spinal metastases to a spinal surgeon. This new practice may lead to a more standardized approach of treating unstable spinal metastases, to improved patient care, and ultimately, to improved clinical outcomes.
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