Abstract
Study Design:
International multicenter prospective observational cohort study on patients undergoing radiation +/− surgical intervention for the treatment of symptomatic spinal metastases.
Objectives:
To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs.
Methods:
Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test.
Results:
A total of 307 patients, including 174 patients who underwent surgery+/− radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/− radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = −0.519, P < 0.001) and the NRS pain score (r = 0.445, P < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment.
Conclusion:
Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.
Keywords: spinal metastases, patient reported outcomes, spinal instability
Introduction
Determining mechanical instability in the management of patients with metastatic spine disease is essential for surgical and radiation decision making. 1 Spinal instability due to metastatic disease was previously defined by the Spine Oncology Study Group as “the loss of spinal integrity as a result of a neoplastic process that is associated with movement related pain, symptomatic or progressive deformity, and/or neurological compromise under physiological loads.” 2 To facilitate improved communication among medical specialists, and allow quantification of the degree of spinal instability, the Spinal Instability Neoplastic Score (SINS) was subsequently developed.
The SINS consists of 6 parameters including the location of the spinal lesion, the quality of the lesion (lytic vs blastic), spinal alignment, degree of vertebral body collapse, involvement of the posterolateral elements and the presence of mechanical pain. The sum of these parameters results in a total score between 0 and 18 which is subdivided in 3 categories of spinal stability; 0-6 representing a stable spinal lesion, 7-12 representing potential spinal instability and 13-18 representing an unstable spinal lesion. 2 It is recommended for patients with a SINS of 7 or higher to be referred to a spinal surgeon to evaluate the need for surgical intervention. As implied in the definition of spinal instability it is thought that higher degrees of spinal instability are associated with higher pain scores, and more significant impairments in patient-reported physical function.3,4 There is, however, a lack of evidence investigating this association.
The primary objective of this study was to determine the association between spinal instability, as defined by the SINS, and baseline patient reported outcomes (PROs), using multicenter prospective study design that includes both patients treated with radiotherapy or surgery+/− radiotherapy. The secondary objective was to determine the correlation between individual SINS components and patient PROs.
Methods
Design
An international multicenter prospective observational cohort study including patients with spinal metastases was conducted at 10 spine centers across North America and Europe (Clinical trials identifier: NCT01825161). Patients between the ages of 18 and 75 years old, and who underwent surgery and/or radiotherapy for the treatment of spinal metastases were eligible for inclusion. Treatment was determined on a case-by-case basis and at the discretion of the treating physician and consisted of either radiotherapy alone, or surgery with or without adjuvant radiotherapy. The research protocol was approved by the research ethics board at each of the participating spine centers. All patients provided written informed consent.
For this predefined study objective, patients were eligible for analysis if they had at least one follow-up by 26 weeks post-treatment. Patients were excluded from the analyses if there was a missing or incomplete SINS or had neurological deficit as the primary indication for treatment (e.g., high grade epidural spinal cord compression).
Outcome Measures
Spinal instability was determined based on the SINS 2 . Baseline demographics, primary tumor, treatment, adverse events (AE), and PROs were prospectively collected for each patient. PROs consisted of the pain numeric rating scale (NRS), the Spine Oncology Study Group Outcome Questionnaire (SOSGOQ2.0), the Short-Form-36 (SF-36v2) and the EuroQol Five dimensions (EQ-5D-3 L). PROs were collected at baseline and during follow-up at 6, 12, and 26 weeks. The primary outcome was the correlation between the total SINS and PROs at baseline. Correlation at follow-up was measured at 12 weeks follow-up. In cases of a missing 12-week visit, the closest visit was used. All patient data was collected and stored in a de-identified format in a secure web-based database (REDCap v6.5.2, Vanderbilt University, Nashville, TN, USA).
Statistical Analysis
Descriptive statistics were used to display demographic and PRO data at baseline. Differences in baseline parameters were analyzed by using a t-test or Wilcoxon rank sum test for continuous variables, whereas the chi-square test or Fisher’s exact test were used for categorical variables. The Spearman rank correlation was used to determine the correlation between the total SINS, the individual SINS components and the different PROsat baseline, and the change in PRO referenced to baseline. The following interpretation of correlation coefficients were applied according to rho <0.2: very weak, 0.20-0.39: weak, 0.40-0.59: moderate, 0.6-0.79: strong, and >0.8 very strong. 5 The Kruskal-Wallis test was applied to determine differences in PROs for the categories of the SINS mechanical pain factors at baseline and during follow-up. Furthermore, ad-hoc pairwise comparisons were performed for the single SINS mechanical pain categories adjusted by Dwass-Steel-Critchlow-Fligner for multiple comparisons. Significance was defined as P < 0.05. All statistical analyses were performed using SAS (version 9.4, SAS Institute Inc., Cary, NC, USA).
Results
A total of 307 patients who were treated for spinal metastases were included in the final analysis, of whom 174 (56.7%) underwent surgery with or without adjuvant radiotherapy and 133 (43.3%) were treated with radiotherapy alone. The most common primary tumor sites were breast (27.4%), lung (16.9%) and kidney (16.9%). At baseline, only 2 patients were classified as ASIA B or C, 31 as ASIA D and 273 as ASIA E. Table 1 describes the baseline characteristics of the study population as a whole and per treatment group.
Table 1.
Baseline Characteristics.
| Characteristic | Surgery (+/− radiotherapy), N = 174 | Radiotherapy alone, N = 133 | Total population, N = 307 |
|---|---|---|---|
| Age at surgery/radiotherapy (years) | |||
| Mean (SD) | 58.3 (10.6) | 60.4 (9.6) | 59.2 (10.2) |
| Gender, n (%) | |||
| Female | 93 (53.4) | 75 (56.4) | 168 (54.7) |
| Male | 81 (46.6) | 58 (43.6) | 139 (45.3) |
| ECOG Classification, n (%) | |||
| 0 | 22 (12.8) | 52 (39.7) | 74 (24.4) |
| 1 | 75 (43.6) | 68 (51.9) | 143 (47.2) |
| 2 | 49 (28.5) | 5 (3.8) | 54 (17.8) |
| 3 | 22 (12.8) | 6 (4.6) | 28 (9.2) |
| 4 | 4 (2.3) | 0 (0.0) | 4 (1.3) |
| Site of the primary cancer, n (%) | |||
| Breast | 35 (20.1) | 49 (36.8) | 84 (27.4) |
| Lung | 35 (20.1) | 17 (12.8) | 52 (16.9) |
| Prostate | 9 (5.2) | 22 (16.5) | 31 (10.1) |
| Kidney | 33 (19.0) | 19 (14.3) | 52 (16.9) |
| Other | 62 (35.6) | 26 (19.5) | 88 (28.7) |
| ASIA Impairment Scale, n (%) | |||
| A-C | 2 (1.1) | 0 (0.0) | 2 (0.7) |
| D | 26 (14.9) | 5 (3.8) | 31 (10.1) |
| E | 146 (83.9) | 127 (96.2) | 273 (89.2) |
| Bilsky epidural spinal cord compression scale | |||
| 0-1c | 105 (62.9) | 118 (95.9) | 223 (76.9) |
| 2-3 | 62 (37.1) | 5 (4.1) | 67 (23.1) |
Abbreviations: SD: Standard deviation. ECOG: Eastern Cooperative Oncology Group. ASIA: American Spinal Injury Association.
In total, 73 (23.8%) patients had a spinal lesion in the SINS 0-6 category, 189 (61.6%) in the SINS 7-12 category and 45 (14.7%) in the SINS 13-18 category. Table 2 displays the distribution of the SINS factors across treatment groups.
Table 2.
Distribution of SINS Factors per Treatment Group.
| Characteristic | Surgery (+/− radiotherapy), N = 174 | Radiotherapy alone, N = 133 | P value |
|---|---|---|---|
| Spine location, n (%) | 174 | 133 | 0.069‡ |
| Rigid (S2-S5) | 1 (0.6) | 7 (5.3) | |
| Semirigid (T3-T10) | 53 (30.5) | 40 (30.1) | |
| Mobile spine (C3-C6, L2-L4) | 42 (24.1) | 35 (26.3) | |
| Junctional (occiput-C2, C7-T2, T11-L1, L5-S1) | 78 (44.8) | 51 (38.3) | |
| Mechanical or Postural pain | 174 | 133 | <.001† |
| Pain-free lesion | 4 (2.3) | 51 (38.3) | |
| Occasional pain but not mechanical | 40 (23.0) | 48 (36.1) | |
| Yes | 130 (74.7) | 34 (25.6) | |
| Bone Lesion Quality, n (%) | 174 | 133 | <.001† |
| Blastic | 16 (9.2) | 28 (21.1) | |
| Mixed (lytic/blastic) | 27 (15.5) | 40 (30.1) | |
| Lytic | 131 (75.3) | 65 (48.9) | |
| Radiographic Spinal Alignment, n (%) | 174 | 133 | 0.013† |
| Normal alignment | 127 (73.0) | 115 (86.5) | |
| De novo deformity (kyphosis/scoliosis) | 38 (21.8) | 16 (12.0) | |
| Subluxation/translation present | 9 (5.2) | 2 (1.5) | |
| Vertebral Body Collapse, n (%) | 174 | 133 | <.001† |
| > 50% collapse | 50 (28.7) | 13 (9.8) | |
| < 50% collapse | 60 (34.5) | 29 (21.8) | |
| No collapse with > 50% body involved | 34 (19.5) | 37 (27.8) | |
| None of the above | 30 (17.2) | 54 (40.6) | |
| Posterolateral Involvement of Spinal Elements | 174 | 133 | 0.055† |
| Bilateral | 64 (36.8) | 32 (24.1) | |
| Unilateral | 68 (39.1) | 60 (45.1) | |
| None of the above | 42 (24.1) | 41 (30.8) | |
| Total SINS categories | 174 | 133 | |
| 0-6 | 18 (10.3) | 55 (41.4) | |
| 7-12 | 118 (67.8) | 71 (53.4) | |
| 13-18 | 38 (21.8) | 7 (5.3) |
‡Fisher’s exact test.
†Chi-Square test.
The total SINS demonstrated a moderate correlation with the baseline SOSGOQ2.0 total score (r = −0.47, P < 0.001), SOSGOQ2.0 physical function (r = −0.50, P < 0.001), SOSGOQ2.0 pain (r = −0.52, P < 0.001), NRS pain (r = 0.45, P < 0.001) and the SF-36 physical component summary (r = −0.46, P < 0.001). A weak correlation was found between the total SINS and the SOSGOQ2.0 social function (r = −0.39, P < 0.001) and a very weak correlation with the SOSGOQ2.0 mental health (r = −0.02, P = 0.75) and the SF-36 mental component summary (r = −0.09, P = 0.13) (Table 3). The combination of the radiographic SINS factors demonstrated only very weak or weak correlation with PRO measures at baseline (Table 3).
Table 3.
Association Between the SINS and Baseline PROs.
| Patient reported outcome at baseline | Total SINS | SINS radiographic subscore* | SINS mechanical pain | |||
|---|---|---|---|---|---|---|
| rho | P-value | rho | P-value | rho | P-value | |
| SOSGOQ2.0 total | −0.47 | <.001 | −0.34 | <.001 | −0.49 | <.001 |
| SOSGOQ physical function 2.0 | −0.50 | <.001 | −0.39 | <.001 | −0.47 | <.001 |
| SOSGOQ pain 2.0 | −0.52 | <.001 | −0.35 | <.001 | −0.58 | <.001 |
| SOSGOQ mental health 2.0 | −0.02 | 0.75 | −0.01 | 0.85 | −0.03 | 0.61 |
| SOSGOQ social 2.0 | −0.39 | <.001 | −0.28 | <.001 | −0.41 | <.001 |
| NRS pain | 0.45 | <.001 | 0.3 | <.001 | 0.54 | <.001 |
| SF-36 PCS | −0.46 | <.001 | −0.30 | <.001 | −0.53 | <.001 |
| SF-36 MCS | −0.09 | 0.13 | −0.06 | 0.29 | −0.09 | 0.12 |
| EQ-5D index | −0.25 | 0.001 | −0.21 | 0.01 | −0.22 | 0.005 |
* SINS radiographic subscore consists of location, lesion quality, degree of vertebral body collapse, spinal alignment and involvement of the posterolateral elements.
Mechanical pain as a single SINS component demonstrated to be moderately correlated with the SOSGOQ2.0 total score (r = −0.49, P < 0.001), SOSGOQ2.0 physical function (r = −0.47, P < 0.001), SOSGOQ2.0 pain (r = −0.58, P < 0.001), NRS pain (r = 0.54, P < 0.001) and the SF-36 physical component summary (r = −0.53, P < 0.001) (Table 4).
Table 4.
Association Between the SINS Individual Components and Baseline Patient Reported Outcomes.
| Individual SINS components | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient reported outcomes at baseline | Spinal location | Mechanical pain | Bone lesion | Alignment | Vertebral body collapse | Posterolateral element involvement | ||||||
| rho | P-value | rho | P-value | rho | P-value | rho | P-value | rho | P-value | rho | P-value | |
| SOSGOQ2.0 total | −0.11 | 0.07 | −0.49 | <.001 | −0.20 | <.001 | −0.26 | <.001 | −0.28 | <.001 | −0.13 | 0.02 |
| SOSGOQ physical function 2.0 | −0.11 | 0.05 | −0.47 | <.001 | −0.21 | <.001 | −0.25 | <.001 | −0.33 | <.001 | −0.18 | 0.002 |
| SOSGOQ pain 2.0 | −0.07 | 0.24 | −0.58 | <.001 | −0.23 | <.001 | −0.24 | <.001 | −0.31 | <.001 | −0.14 | 0.02 |
| SOSGOQ mental health 2.0 | −0.03 | 0.62 | −0.03 | 0.61 | −0.04 | 0.54 | −0.04 | 0.45 | 0.05 | 0.41 | 0.01 | 0.85 |
| SOSGOQ social 2.0 | −0.10 | 0.07 | −0.41 | <.001 | −0.17 | 0.004 | −0.18 | 0.002 | −0.25 | <.001 | −0.01 | 0.09 |
| NRS pain | 0.004 | 0.95 | 0.54 | <.001 | 0.20 | <.001 | 0.18 | 0.002 | 0.30 | <.001 | 0.14 | 0.02 |
| SF-36 PCS | −0.07 | 0.25 | −0.53 | <.001 | −0.16 | 0.005 | −0.22 | <.001 | −0.30 | <.001 | −0.10 | 0.09 |
| SF-36 MCS | −0.05 | 0.44 | −0.09 | 0.12 | −0.003 | 0.96 | −0.01 | 0.84 | −0.03 | 0.66 | −0.09 | 0.14 |
| EQ-5D index | −0.01 | 0.94 | −0.22 | 0.005 | 0.03 | 0.68 | −0.16 | 0.04 | −0.21 | 0.006 | −0.11 | 0.16 |
At baseline, the median SOSGOQ total score for patients with mechanical pain was 50 as compared to 59.5 for patients with non-mechanical pain, and 80.5 for patients with pain free spinal lesions (P < 0.001) (Table 5). At 12 weeks follow-up, the presence of mechanical pain at baseline was associated with significant improvements in the SOSGOQ2.0 total score, SOSGOQ2.0 pain score, SOSGOQ2.0 physical functions and improvements in the NRS pain scale in both treatment groups (Table 6). On the contrary, patients with a pain-free lesion experienced a decline in SOSGOQ2.0 total score, and all individual SOSGOQ2.0 domains after surgical treatment.
Table 5.
The Association Between the Presence of Mechanical Pain and Patient Reported Outcomes at Baseline.
| Median per mechanical pain component | Kruskal-Wallis test | |||
|---|---|---|---|---|
| Patient reported outcomes | Pain-free (0) | Occasional pain (1) | Mechanical pain (3) | P-value |
| SOSGOQ2.0 total | 80.5 | 59.5 | 50 | <.001 |
| SOSGOQ physical function 2.0 | 92 | 67 | 54 | <.001 |
| SOSGOQ pain 2.0 | 90 | 45 | 35 | <.001 |
| SOSGOQ mental health 2.0 | 63 | 63 | 63 | 0.72 |
| SOSGOQ social 2.0 | 92 | 67 | 58 | <.001 |
| NRS pain | 1 | 5 | 7 | <.001 |
| EQ-5D index | 0.82 | 0.71 | 0.51 | <.001 |
| SF-36 PCS | 47.2 | 34.0 | 29.1 | <.001 |
| SF-36 MCS | 47.6 | 46.3 | 44.3 | 0.30 |
Table 6.
Association Between SINS Mechanical Pain and Median Change in Patient Reported Outcomes at at 12 Weeks Follow-Up.a
| Median per mechanical pain component | Kruskal-Wallis test | |||
|---|---|---|---|---|
| Change in PRO | Pain-free (0) | Occasional pain (1) | Mechanical pain (3) | P-value |
| SOSGOQ total 2.0 change | 0 | 2 | 14 | <.001 |
| SOSGOQ physical function 2.0 change | -4 | 0 | 5 | <.001 |
| SOSGOQ pain 2.0 change | 0 | 10 | 25 | <.001 |
| SOSGOQ mental health 2.0 change | 0 | 0 | 6 | 0.138 |
| SOSGOQ social 2.0 change NRS pain change | 0 | 0 | 17 | <.001 |
| 0 | −1 | −3 | <.001 | |
| EQ-5D index change | 0.00 | 0.00 | 0.18 | <.001 |
| SF-36 PCS change | −2.0 | −1.0 | 2.0 | <.001 |
| SF-36 MCS change | −0.3 | 0.2 | 3.1 | 0.039 |
a 0 representing no changes in score between baseline and 12 weeks follow-up.
An analysis of variance demonstrated that the total SINS had a significant and large effect on the SOSGOQ2.0 total score (F value = 18.8, P < 0.001) and SOSGOQ2.0 pain score (F value = 23.4, P < 0.001) at baseline, as compared to other factors such as ECOG (F value = 7.6, P < 0.001; F value = 4.4, P = 0.002), gender (F value = 0.4, P = 0.56; F value = 1.5, P = 0.22), age (F value = 0.6, P = 0.45; F value = 0.5, P = 0.48), duration of symptoms (F value = 1.9, P = 0.15; F value = 4.3, P = 0.01), primary tumor type (F value = 0.4, P = 0.98; F value = 0.6, P = 0.84), ASIA score (F value = 0.1, P = 0.94; F value = 0.2, P = 0.89) and degree of epidural spinal cord compression (F value = 0.3, P = 0.92; F value = 0.8, P = 0.58).
Discussion
In this international multicenter prospective observational cohort study we examined the association between mechanical instability as defined by the SINS and PROs. In addition, we examined the association between the individual SINS components and PROs at baseline and 12 weeks follow-up.
In 2 previous studies, Hussain et al examined the association between the SINS and PROs including the Brief Pain Inventory (BPI) and the MD Anderson Symptom Inventory-Spine Tumor (MDASI) questionnaire, in a cohort of patients who underwent surgical treatment for spinal metastases.3,4 They reported significant yet weak associations between the total SINS and BPI worst pain (r = 0.13), BPI average pain (r = 0.20), MDASI pain (r = 0.19) and MDASI spine pain (r = 0.13) component scores. Our data demonstrated moderate associations between the SINS and the SOSGOQ2.0 pain (r = −0.54) and the NRS pain score (r = 0.49). The stronger associations in our study, compared to the study of Hussain et al, may be explained by the use of the SOSGOQ2.0 as an outcome measure. In contrast to the BPI, the SOSGOQ2.0 is a spine-specific PRO measure and previously demonstrated to be a valid, reliable and a sensitive measure to evaluate health-related quality of life (HRQOL) in patients with spinal metastases. 6 Although the MDASI-spine tumor specific questionnaire may be regarded as spine specific, the MDASI spine pain component is based on a single question regarding the level of radiating spine pain. 7 Patients may, however, not necessarily experience radiating pain but rather non-radiating spine pain. This question might therefore not be specific and sensitive enough to measure the association. On the contrary, the SOSGOQ2.0 pain domain consist of 5 questions to assess spine related pain. Similarly, Hussain et al demonstrated a significant but weak to very weak association between the SINS and physical function as measured by the MDASI activity and walking subscores.3,4 Our data demonstrated moderate associations between the SINS and the SOSGOQ2.0 physical function and the SF-36 physical component scores. The concept of spinal instability can explain the associations found between the total SINS and pain and physical function, as several investigators have suggested that the presence of movement related pain with relief by recumbence is the key identifying symptom of spinal instability.8-10 This is supported by similar strength associations between mechanical pain and PROs as compared to associations between the total SINS and PROs.
In addition to the total SINS, the association between the combination of the radiographic SINS parameters and PRO measures was investigated in our study. Only weak to moderate associations were found between the radiographic parameters and patient report pain and physical function. The radiographic SINS factors can be divided into those that are regarded as a risk of spinal instability (e.g. mobile spine location), versus factors that express a degree of spinal instability (e.g. mechanical pain). These subtle differences between the SINS factors may explain the lower associations between the sum of the radiographic SINS factors and PROs.
The SINS distinquishes between 3 different categories of spinal (in)stability. However, the vast majority of patients who require treatment with either surgery and/or radiation therapy fall into the category of potential spinal instability (SINS 7-12). Evidence for treatment decision making in this group of patients with potentially unstable spinal metastases is yet limited.4,11 In a previous study we attempted to further characterize this group by investigating HRQOL outcomes in patients with potentially unstable spinal metastases (SINS 7-12) treated either with surgery or radiotherapy alone. We demonstrated that surgically treated patients experienced significant and sustained improvements in HRQOL. However, when looking at the SINS characteristics of the surgical cohort, patients were more likely to have mechanical back pain, a lytic lesion, vertebral compression fractures and a higher median SINS score. 11 Hussain et al, further examined this group of patients by dividing the potentially unstable group further into a “low potentially unstable (SINS 7-9)” and a “high potentially unstable (SINS 10-12)” group to investigate the association with surgical outcomes. 4 The authors demonstrated that the patients in the high potentially unstable group experienced significantly greater improvements after surgery compared to patients in the low potentially unstable group. The results of both studies suggest the need for a revision of the current composition of the SINS score as patients with lower scores in the potentially unstable category seem to be of lower risk of mechanical instability as compared to patients with higher scores in the potentially unstable category.
In contrast to the moderate associations between SINS and pain and physical function, only weak to very weak associations between the SINS and the SOSGOQ2.0 mental health and the SF-36 mental component scores were observed. These low associations may be explained by the multi-factorial nature of mental health in cancer patients.12,13 Other aspects of patient’s disease status and concomitant treatments are likely to influence mental health status rather than spinal instability as reflected by the SINS.
Generally two different types of pain from spinal metastases can be discriminated; local tumor derived pain and pain as result of the loss of spinal integrity. Local tumor pain is generally thought to be caused by local stretching of the periosteum and invasion of inflammatory mediators.14,15 On the other hand, metastatic disease can lead to bone loss and subsequently compromise mechanical integrity leading to painful micromotion within bone. 15 Mechanical pain is thought to be severe and less responsive to medical management and, therefore, surgical intervention is often indicated. Our data demonstrated that patients with mechanical pain had significantly higher pain scores as compared to patients with non-mechanical back pain or no pain. In addition, the SINS demonstrated to have the largest effect on PROs as compared to other factors that are known to influence quality of life such as performance status and gender. These results support the hypothesis of the debilitating effects of mechanical instability on patient quality of life.
This study has several strengths enhancing the generalizability of the results. First, 10 centers contributed resulting in a relatively large sample size for this challenging patient population. Second, both patients who were treated with surgery and patients treated with radiotherapy alone were included in the study. This resulted in a more even distribution of SINS across the study population and a heterogenous yet representable patient population. Lastly, the SOSGOQ2.0 and the SF-36 were used to evaluate patient reported HRQOL. The SOSGOQ2.0 is a valid and spine specific PRO measure and the SF-36 is a validated generic outcome measure.
In conclusion, this study investigated the association between mechanical instability as represented by the SINS and PRO measures at baseline using an international multicenter prospective observational cohort study. We demonstrated that the total SINS and the presence of mechanical pain are moderately yet significantly associated with pain and physical function. In addition, the SINS demonstrated to have the largest effect on HRQOL as measured by the SOSGOQ2.0 total score and SOSGOQ2.0 pain score.
Acknowledgments
We are grateful to the Orthopaedic Research and Education Foundation (OREF) for their grant to support this study. We are grateful to the collaborating centers’ local clinical research personnel and support staff for their active participation. This study was organized and funded by AO Spine International, through the AO Spine Knowledge Forum Tumor, a focused group of international spine oncology experts. Study support was provided directly through the AO Spine Research Department and the AO Innovation Translation Center, Clinical Evidence. We thank Christian Knoll for performing the statistical analysis.
Footnotes
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Versteeg reports consulting and travel accommodations from AO Spine International. Dr. Sahgal reports past educational seminars with Elekta AB, Accuray Inc., and Varian medical systems; research grant with Elekta AB; travel accommodations and expenses from Elekta, Varian and AO Spine International; and belongs to the Elekta MR Linac Research Consortium. Dr. Laufer reports consulting for Medtronic, Globus, Brainlab, DePuy/Synthes and Spinewave. Dr. Rhines reports educational commitments with Stryker, which are outside the submitted work. Dr. Boriani reports educational commitments with Stryker, which are outside the submitted work. Dr. Sciubba reports consulting and royalties from Depuy-Synthes, Stryker and Baxter, which are all outside the submitted work. Dr. Fisher reports consulting and royalties from Medtronic and Nuvasive; research grants from OREF; and fellowship support paid to institution from AO Spine and Medtronic, which are all outside the submitted work. No other relevant disclosures were reported.
Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: A research grant was received from the Orthopaedic Research and Education Foundation. This study was organized and funded by AO Spine International, through the AO Spine Knowledge Forum Tumor.
ORCID iDs: Anne L. Versteeg, MD, PhD, MHSc 
https://orcid.org/0000-0003-3251-9694
Daniel M. Sciubba, MD
https://orcid.org/0000-0001-7604-434X
Aron Lazary, MD
https://orcid.org/0000-0002-0157-719X
Michael G. Fehlings, MD, PhD
https://orcid.org/0000-0002-5722-6364
Paul M. Arnold, MD
https://orcid.org/0000-0002-4622-7695
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