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Clinical Study| Volume 20, ISSUE 1, P22-31, January 2020

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Sarcopenia, but not frailty, predicts early mortality and adverse events after emergent surgery for metastatic disease of the spine

Published:September 01, 2019DOI:https://doi.org/10.1016/j.spinee.2019.08.012

      Abstract

      Background context

      Frailty and sarcopenia variably predict adverse events (AEs) in a number of surgical populations.

      Purpose

      The aim of this study was to investigate the ability of frailty and sarcopenia to independently predict early mortality and AEs following urgent surgery for metastatic disease of the spine.

      Study Design

      A single institution, retrospective cohort study.

      Patient Sample

      One hundred eight patients undergoing urgent surgery for spinal metastases from 2009 to 2015.

      Outcome Measures

      The incidence of AEs including 1- and 3-month mortality.

      Methods

      Sarcopenia was defined using the L3 Total Psoas Area/Vertebral body Area (L3-TPA/VB) technique on CT. The modified Frailty Index (mFI), Metastatic Frailty Index (MSTFI) and the Bollen prognostic scales were calculated for each patient. Additional data included demographics, tumor type and burden, neurological status, the extent of surgical treatment and the use of radiation-therapy. Spearman correlation test, logistic regression and Kaplan-Meier were used to study the relation between the outcomes measures and potential predictors (L3-TPA/VB, MSTFI, mFI, and the Bollen prognostic scales).

      Results

      Eighty-five percent of patients had at least one acute AE. Sarcopenia predicted the occurrence of at least one postop AE (L3-TPA/VB, 1.07±0.40 vs. 1.25±0.52; p=.031). Sarcopenia (L3-TPA/VB) and the degree of neurological impairment were predictive of postoperative AE but MFI or MSTFI were not. Sarcopenia predicted 3-month mortality, independent of primary tumor type (L3-TPA/VB: 0.86±0.27 vs. 1.12±0.41; p<.001). Kaplan-Meyer analysis showed L3-TPA/VB and the Bollen Scale to significantly discriminate patient survival.

      Conclusions

      Sarcopenia, easily measured by the L3-TPA/VB on conventional CT, predicts both early postoperative mortality and adverse events in patients undergoing urgent surgery for spinal metastasis, thus providing a practical tool for timely therapeutic decision-making in this complex patient population.

      Keywords

      Introduction

      Surgical intervention is a well-established component of the treatment algorithm for spinal metastasis, along with radiation therapy and chemotherapy. Symptomatic spinal cord compression and mechanical instability are the primary surgical indications in the metastatic spine disease population. Surgery can be effective in maintaining a patient's function [
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      ]. Metastatic spine disease patients often present with indications for urgent surgery such as progressive neurological deterioration. However, metastatic disease burden and life-expectancy must be weighed against potential functional improvement, although surgical decision-making must be done urgently with often incomplete information. Several mortality predictive scores for spinal metastatic patient have been described with limited success [
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      Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1,043 patients.
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      Predictive value of six prognostic scoring systems for spinal bone metastases: an analysis based on 1379 patients.
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      Surgical strategy for spinal metastases.
      ]. To date, none of these provide any practical guidance in the acute setting, as to the urgency and appropriate extent of surgery.
      Frailty denotes a state of weakened reserve against stressors and may occur independent of and out of proportion to chronological age [
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      Frailty assessment in elderly people.
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      ]. One conceptual model of frailty is the theory of the accumulation of deficits which led to the development of frailty indices including the Modified Frailty Index (mFI) [
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      ] and the Metastatic Spinal Tumor Frailty Index (MSTFI) [
      • De la Garza Ramos R
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      Development of a metastatic spinal tumor frailty index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery.
      ]. Derived from large databases, these indexes have been shown to predict adverse events and mortality following spine surgery [
      • De la Garza Ramos R
      • Goodwin CR
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      Development of a metastatic spinal tumor frailty index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery.
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      • Ali R
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      • Nerenz DR
      • Antoine HJ
      • Rubinfeld I
      Use of the modified frailty index to predict 30-day morbidity and mortality from spine surgery.
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      • Phan K
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      Frailty is associated with morbidity in adults undergoing elective anterior lumbar interbody fusion (ALIF) surgery.
      ,
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      Frailty index as a predictor of adverse postoperative outcomes in patients undergoing cervical spinal fusion.
      ]. Related to this, sarcopenia is defined as a progressive loss of skeletal muscle mass, strength, and power and is one manifestation of frailty [
      • Choi Y
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      Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression.
      ,
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      Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair.
      ,
      • Mitsiopoulos N
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      Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography.
      ,
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      Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer.
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      The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.
      ,
      • Tan BH
      • Birdsell LA
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      • Fearon KC
      Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer.
      ]. In the oncologic population, sarcopenia is commonly referred to as cancer cachexia. In prior studies, sarcopenia has been evaluated in a practical fashion by measuring the total area of the psoas muscle on axial computed tomography (CT) scanning although consensus on the appropriate threshold is lacking. Frailty has been shown to predict adverse outcomes in multiple spinal surgical populations [
      • De la Garza Ramos R
      • Goodwin CR
      • Jain A
      • Abu-Bonsrah N
      • Fisher CG
      • Bettegowda C
      • et al.
      Development of a metastatic spinal tumor frailty index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery.
      ,
      • Ali R
      • Schwalb JM
      • Nerenz DR
      • Antoine HJ
      • Rubinfeld I
      Use of the modified frailty index to predict 30-day morbidity and mortality from spine surgery.
      ,
      • Shin JI
      • Kothari P
      • Phan K
      • Kim JS
      • Leven D
      • Lee NJ
      • et al.
      Frailty index as a predictor of adverse postoperative outcomes in patients undergoing cervical spinal fusion.
      ,
      • Flexman AM
      • Charest-Morin R
      • Stobart L
      • Street J
      • Ryerson CJ
      Frailty and postoperative outcomes in patients undergoing surgery for degenerative spine disease.
      ,
      • Leven DM
      • Lee NJ
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      • Steinberger J
      • Guzman J
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      • et al.
      Frailty index is a significant predictor of complications and mortality after surgery for adult spinal deformity.
      ]. In the metastatic spine disease population, frailty and sarcopenia may be potentially useful tools to guide surgical candidacy, urgency and planning, yet, their usefulness to predict mortality and AEs remains unknown in this challenging population.
      The objectives of this study were to determine the relationship among sarcopenia, frailty indices, and the Bollen scale with mortality and acute care AEs in patients undergoing surgery for metastatic disease of the spine. We hypothesized that the newer frailty indices (MFI and MSTFI) and sarcopenia measures would discriminate better in the metastatic spine disease population than the historical Bollen Prognostic Scale.

      Material and methods

      Study population

      We included all consecutive patients with metastatic spinal disease, admitted at a quaternary referral center over 8 years between January 1, 2009 and December 31, 2016 in this retrospective cohort study. The study was approved by the Institutional Research Ethics Board with a waiver for informed consent obtained for each individual patient. We included all patients admitted with a diagnosis of metastatic spine disease who required urgent spine surgery because of progressive neurological deterioration or intractable mechanical pain. Patients were excluded if they were treated nonsurgically, had intradural malignancy, primary neoplasm of the spine, a destructive lesion at the L3 level precluding measurement of the L3-TPA/VB ratio, or if a lumbar CT scan was not available within 6 months of their index admission.

      Patient and surgical data

      The following data were retrieved from our local prospective spine registry; demographics, American Spinal Injury Association (ASIA) classification, surgical procedures (type of surgery, surgical approach, and duration of surgery), adverse events, and mortality. Data regarding primary tumor site, the use of radiation therapy, frailty, Surgical Invasiveness Index (SII), and sarcopenia measures were extracted from the electronic medical record.
      Sarcopenia: Sarcopenia was assessed by measuring the right and left psoas muscle area on the axial image in the middle of the L3 vertebral body on a standard abdominal CT scan obtained within 6 month of the index hospital admission. Measurements were conducted in a semiautomated fashion with manual outlining of muscle borders and L3 vertebral body followed by automated volumetric analysis. The imaging settings were adjusted to −30 and 110 Hounsfield units (HU) to exclude vasculature, bony structures, and fat infiltration for outlining of the muscle borders. For each patient, we calculated the ratio of the sum of the left and right psoas muscle area divided by the area of the L3 vertebral body (L3-TPA/VBA) as depicted in Figure 1. This measurement technique was previously shown to have good inter-rater reliability [
      • Gakhar H
      • Dhillon A
      • Blackwell J
      • Hussain K
      • Bommireddy R
      • Klezl Z
      • et al.
      Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression.
      ]. The time-dependent changes in muscle mass in oncologic patients are a well-known phenomenon. To account for that, the effect of sarcopenia on survival was analyzed using the day of imaging (as opposed to the admission day) as a reference point for survival time.
      Fig 1
      Fig. 1Measurement technique of psoas surface area. All measurements were made using the surface area measurement tool included in the PACS software. The transverse CT scan cut at the level of the middle of the L3 vertebral body was used to measure area. The L3 Total Psoas Area/ Vertebral Body Area (L3-TPA/VBA) was the sum of the right (A) and left (B) psoas area was divided by the area of the L3 vertebral body.
      Frailty indexes: Frailty was evaluated with the previously described mFI [
      • Rockwood K
      • Song X
      • Mitnitski A
      Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey.
      ] and the MSFTI [
      • De la Garza Ramos R
      • Goodwin CR
      • Jain A
      • Abu-Bonsrah N
      • Fisher CG
      • Bettegowda C
      • et al.
      Development of a metastatic spinal tumor frailty index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery.
      ]. The MFI consists of 11 variables including comorbidities and deficits. The MFI score is calculated as a proportion of the number of reported variables divided by the number of variables assessed. Patients were classified as not frail (mFI=0), pre-frail (mFI>0 and <0.21), and frail (≥0.21) based on previous data defining frailty as an index greater than or equal to 0.21 [
      • Rockwood K
      • Song X
      • Mitnitski A
      Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey.
      ]. The MSTFI is a metastatic spine tumor specific frailty index designed to predict surgical morbidity, mortality and length of hospital stay [
      • De la Garza Ramos R
      • Goodwin CR
      • Jain A
      • Abu-Bonsrah N
      • Fisher CG
      • Bettegowda C
      • et al.
      Development of a metastatic spinal tumor frailty index (MSTFI) using a nationwide database and its association with inpatient morbidity, mortality, and length of stay after spine surgery.
      ]. The score consists of 9 weighted variables, with a range of 0 to 10, higher score meaning increased frailty. The malnutrition variable was omitted from the score for the current study due to insufficient data.
      Bollen prognostic scale (BPS): The BPS is a specific prognostic scale designed to stratify patient survival. The BPS was chosen due to its ease in clinical application and its adaptability to improvement in cancer care over time [
      • Bollen L
      • Wibmer C
      • Van der Linden YM
      • Pondaag W
      • Fiocco M
      • Peul WC
      • et al.
      Predictive value of six prognostic scoring systems for spinal bone metastases: an analysis based on 1379 patients.
      ]. The scale classifies patients into 4 prognostic categories (from best to worst prognosis: A, B, C and D) based on 3 clinical variables: clinical profile of the primary tumor, Karnofsky Performance Score [
      • Mor V
      • Laliberte L
      • Morris JN
      • Wiemann M
      The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting.
      ], and the presence of visceral or brain metastasis [
      • Bollen L
      • van der Linden YM
      • Pondaag W
      • Fiocco M
      • Pattynama BP
      • Marijnen CA
      • et al.
      Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1,043 patients.
      ].

      Postoperative outcomes

      Mortality was analyzed 1 and 3 months after the day of admission to hospital (doADM). The time point of reference for calculation of survival was the doADM for all analysis except for L3 Total Psoas Area/ Vertebral Body Area (L3-TPA/VBA) where we used the day of CT-Scan (doCT-S).
      AEs were collected using the Spine Adverse Event Severity System (SAVES) V2.0 [
      • Street JT
      • Lenehan BJ
      • DiPaola CP
      • Boyd MD
      • Kwon BK
      • Paquette SJ
      • et al.
      Morbidity and mortality of major adult spinal surgery. A prospective cohort analysis of 942 consecutive patients.
      ]. SAVES allows systematic prospective collection of postoperative AEs in spinal surgery. Its sensibility to detect an extensive variety of postoperative AEs in various settings and populations of spinal patient was previously demonstrated [
      • Dea N
      • Versteeg A
      • Fisher C
      • Kelly A
      • Hartig D
      • Boyd M
      • et al.
      Adverse events in emergency oncological spine surgery: a prospective analysis.
      ,
      • Street JT
      • Lenehan BJ
      • DiPaola CP
      • Boyd MD
      • Kwon BK
      • Paquette SJ
      • et al.
      Morbidity and mortality of major adult spinal surgery. A prospective cohort analysis of 942 consecutive patients.
      ,
      • Charest-Morin R
      • Street J
      • Zhang H
      • Roughead T
      • Ailon T
      • Boyd M
      • et al.
      Frailty and sarcopenia do not predict adverse events in an elderly population undergoing non-complex primary elective surgery for degenerative conditions of the lumbar spine.
      ,
      • Karstensen S
      • Bari T
      • Gehrchen M
      • Street J
      • Dahl B
      Morbidity and mortality of complex spine surgery: a prospective cohort study in 679 patients validating the Spine AdVerse Event Severity (SAVES) system in a European population.
      ].

      Statistical analysis

      Data are summarized as mean (standard deviation) or as median (interquartile range [IQR]). Logistic regression with backward stepwise elimination was used to determine the impact of sarcopenia and frailty on the occurrence of AEs. Spearman Correlation were used to assess the relationship between the number of postop AEs and the different predictors studied (L3-TPA/VBA, Bollen, mFI, MSTFI and SII). Statistical analysis of survival included Kaplan-Meier curves used to determine differences in survival between sarcopenia categories with the Gehan-Breslow-Wilcoxson tests. A two-tailed p<.05 was considered statistically significant for all comparisons. All data were analyzed using SPSS (version 24.0 for Mac; IBM, Chicago, Il) and Excel (version 15.2 for Mac; Microsoft, Redmond, WA).

      Results

      We screened the 271 admissions for spinal metastasis within our database and after elimination of duplicated and repeated admissions we included 169 initial surgical admissions for spinal metastasis. Of these, 61 patients were excluded, leaving 108 patients included in our analysis (Fig. 2). Fifty-three percent were male, and the average age was 61.5 (SD 11.5) years. The most common primary tumor location was breast (22%), followed by lung (17%), and kidney (16%). Thirty-six patients (33%) had solitary vertebral metastasis, 26 (24%) patients had concomitant metastatic node involvement and 46 (43%) had visceral metastases. Detailed demographic data are displayed in Table 1.
      Fig 2
      Fig. 2Flow chart of patients included and excluded in our study. Sixty-one were excluded from the 169 patients considered for inclusion. The exclusion criteria were: patients with no valid CT-Scans, patients with primary tumor of the spine, patients with significant L3 metastatic involvement and patients admitted for non-surgical management of their spinal metastasis. *Six patients had more than one exclusion criteria.
      Table 1Demographic and clinical variables of 108 surgical patients with spinal metastasis
      VariableIncluded patientExcluded patient
      Gender (male)57/108 (52.8%)30/61 (49.2%)
      Age (years)62.5 (35–84)60.9 (19.3-85.1)
      ASIA
      A0/108 (0.0%)1/61 (1.6%)
      B2/108 (1.9%)2/61 (3.3%)
      C14/108 (13.0%)3/61 (4.9%)
      D43/108 (39.8%)20/61 (32.8%)
      E49/108 (45.4%)35/61 (57.4%)
      Surgical site
      Cervical15/108 (13.9%)5/28 (17.9%)
      Thoracic66/108 (61.1%)20/28 (71.4%)
      Lumbar25/108 (23.1%)3/28 (10.7%)
      Sacral2/108 (1.9%)0
      Tumour by group
      Kidney17/108 (15.7%)6/61 (9.8%)
      Lung18/108 (16.7%)11/61 (18.0%)
      Breast24/108 (22.2%)11/61 (18.0%)
      Prostate13/108 (12.0%)6/61 (9.8%)
      Other36/108 (33.3%)27/61 (44.3%)
      SII18.3 (10-27)N/A
      Radiation therapy
      Pre-Op17/108 (15.7%)6/28 (21.4%)
      Post-Op56/108 (51.8%)14/28 (50.0%)
      Pre- and postop9/108 (8.3%)8/28 (28.6%)
      None
      No radiation therapy during the study period. RT: Radiation Therapy. Statistical difference between included and excluded patients was always p>0.2 except for radiation therapy distribution (p<.001)
      26/108 (24.1%)1/33 (3.0%)
      RT/Non-opN/A25/33 (75.8%)
      No RT/Non-opN/A6/33 (18.2%)
      low asterisk No radiation therapy during the study period. RT: Radiation Therapy.Statistical difference between included and excluded patients was always p>0.2 except for radiation therapy distribution (p<.001)
      Various surgical procedures were performed including 3 anterior cervical decompression and fusions, 6 posterior cervical decompressions with instrumentation, 8 combined (anterior/posterior) cervical procedures, 5 posterior thoracolumbar decompressions without fusion, 43 posterior thoracolumbar decompression and instrumentation and 43 posterior thoracolumbar instrumentation with reconstruction of the anterior column. The mean operative time was 276±125 minutes. The median SII was 19 (range 10–27). The median length of hospital stay was 22 days (IQR 12–35).

      Adverse events

      A total of 287 AEs were observed in 92 patients (85%) with a mean of 2.6 AEs per patient. The most common postoperative AEs were urinary tract infection (41%), electrolyte imbalance (27%), and delirium (23%). Figure 3 displays the incidence of specific AE categories. The distribution of frailty indexes Bollen prognostic categories and sarcopenia are presented in Table 2. Patients who experienced at least 1 AE had a significantly a lower mean L3-TPA/VBA compared with patients who had no AEs (1.07±0.40 vs. 1.25±0.52; p=.031). Conversely, MSTFI, mFI, and Bollen Scale were not significantly associated with having an adverse event AEs (Table 3). L3-TPA/VBA and MFI were significantly correlated with the number of AEs experienced (rs=−0.292; p=.002 and rs=0.197; p=.042, respectively) but not the Bollen Scale, MSTFI and SII (Table 4).
      Fig 3
      Fig. 3This bar graph displays global AE rate and clinically relevant AE rate. Intra-operative technical AEs (marked with *) were excluded of our statistical analysis. The category other AEs corresponds to AEs not categorized in the SAVEs form.
      Table 2Distribution of frailty index (mFI, MSTFI) prognostic score (Bollen Categories) and sarcopenia (L3-TPA/VBA) among 108 surgical patients with spinal metastasis
      Predictor108 included patients
      MSTFI score
      017/108 (15.7%)
      133/108 (30.6%)
      221/108 (19.4%)
      326/108 (24.1%)
      MFI
      020/108 (18.5%)
      0.0953/108 (49.1%)
      0.1819/108 (17.6%)
      0.279/108 (8.3%)
      0.365/108 (4.6%)
      0.451/108 (0.9%)
      Bollen categories
      A12/108 (11.1%)
      B25/108 (23.1%)
      C43/108 (39.8%)
      D27/108 (25.0%)
      L3-TPA/VBA
      Median0.9294 (0.4849–2.6197)
      1rst Quartile0.7298 (0.4849–0.8072)
      2nd Quartile0.8734 (0.8108–0.9292)
      3rd Quartile1.0788 (0.9297–1.2440)
      4rth Quartile1.5304 (1.2481–2.6197)
      Table 3Comparison of L3-TPA/VBA, MSTFI, MFI, Bollen, and SII Scale values (mean ± SD) among patients based on AEs, 1-month mortality (1m mortality) and 3-month mortality (3m mortality)
      L3-TPA/VBAMSTFIMFIBollenSII
      AE (n=82)1.07±0.401.62±1.030.12±0.102.10±0.8118.2±3.9
      No AE (n=26)1.25±0.521.28±1.10.09±0.72.36±0.8118.5±3.8
      p=.031p=.74p=.11p=.64p=.72
      1m mortality (n=13)0.72±0.121.85±0.900.14±0.072.38±0.8718.3±3.8
      >1m mortality (n=95)1.08±0.401.59±1.040.12±0.102.06±0.8018.2±3.6
      p=.008p=.44p=.12p=.16p=.91
      3m mortality (n=28)0.86±0.272.04±0.990.14±0.092.43±0.7418.1±3.9
      >3m mortality (n=80)1.12±0.411.47±1.000.11±0.101.99±0.8118.6±3.7
      p<.001p=.012p=.068p=.013p=.84
      For L3-TPA/VBA, 1-month and 3-month mortality were calculated from the imaging day.
      Table 4Bivariate correlation studies between predictive tools and number of postop adverse events
      AE Number
      L3-TPA/VBArs-0.292
      p-value0.002
      Bollenrs0.08
      p-value0.41
      mFIrs0.197
      p-value0.042
      MSTFIrs0.166
      p-value0.087
      SIIrs-0.142
      p-value0.144
      L3-TPA/VBA and mFI both showed statistically significant correlation with the number of postoperative adverse events. rs: Spearman correlation coefficient.
      Multivariate logistic regression analysis using the backward elimination procedure retained L3-TPA/VBA and preoperative neurological impairment as independent predictors of experiencing one or more AEs (Table 5). MSTFI, mFI, SII, Bollen Score, tumor grade, extent of disease, age, and gender were excluded from the model. For every 1 unit increase in L3-TPA/VBA, the odds of experiencing an adverse event was reduced by 0.29 (95% confidence interval [CI] 0.09–0.93; p=.037). The presence of neurological impairment was associated with an adjusted odds ratio of 4.2 (95% CI 1.5–11.3, p=.005) of having an adverse event.
      Table 5Logistic regression analysis for postoperative occurrence of adverse events
      95% intervalOdds ratiop-value
      L3-TPA/VBA
      Per 1 unit increase. MSTFI, mFI, SII, Bollen Score, tumor grade, extent of disease, age and gender were excluded from the model based on lack of significance (p>0.05).
      0.090.930.290.037
      Neuro Impairment1.5411.34.170.005
      low asterisk Per 1 unit increase.MSTFI, mFI, SII, Bollen Score, tumor grade, extent of disease, age and gender were excluded from the model based on lack of significance (p>0.05).

      Mortality

      At the time of the study, 42% of the patients were still alive. The overall median survival was 9 (IQR 3.0–23.5) months. L3-TPA/VBA was significantly lower in those who died within 1 month (0.72±0.12 vs. 1.08±0.40; p=.008) and 3 months (0.86±0.27 vs. 1.12±0.41; p<.001) of surgery. Similarly, MSTFI (2.04±0.99 vs. 1.47±1.00; p=.012) and Bollen Prognostic Scale were statistically higher for patients who died within 3 months of surgery (Table 3).
      Kaplan-Meier Curves demonstrated differences in cumulative survival when patients were stratified using Bollen Scale (p=.004) and L3-TPA/VBA (p=.04), but not the mFI (p=.399) and MSTFI (p=.096) (Fig. 4, Fig. 5). Further exploratory analysis of L3-TPA/VBA showed that the greatest difference in survival was between the first quartile (1rst quartile of L3-TPA/VBA=0.80712) and the rest (p=.006)
      Fig 4
      Fig. 4Kaplan Meier Curves of first psoas quartile (green curve) compared with higher quartiles (blue curve). Survival curves were significantly different (p=0.040), specifically when the first quartile (L3-TPA/VBA<0.81) was compared to the other higher quartiles (p=0.006). There was no difference among the 3 other quartiles.
      Fig 5
      Fig. 5Kaplan Meier Curves by Bollen Categories. Survival was significantly different between the Bollen Categories (p=.004).

      Discussion

      Determination of the risk/benefit balance of surgery is a major challenge in the care of metastatic spine disease patients. Surgery is often urgent, usually requiring neural decompression/separation from the tumor mass, and stabilization. The invasiveness of this surgery can be significant, with a high rate of complications. In patients with limited life expectancy, it is critical that we understand the relative risks and benefits to inform clinical decisions. In this study, we evaluated a number of putative predictors of early mortality and AEs in metastatic spine disease patients undergoing urgent surgery. Our results indicate adverse events are common in this population, and that sarcopenia (as assessed using the L3-TPA/VBA ratio) was an independent predictor of experiencing an adverse event, as well as mortality at 1 and 3 months. Similarly, frailty predicted poor outcomes; the mFI independently predicted the total number of adverse events, and the MSTFI was associated with mortality at 3 months. Overall, our study suggests that the L3-TPA/VBA ratio is a clinically useful predictor of early mortality and AES in metastatic spine disease patients undergoing urgent spine surgery.
      Previous authors have arbitrarily defined a threshold of 3-months life expectancy for surgical intervention in this population, based on the relative risks and benefits [
      • Tokuhashi Y
      • Matsuzaki H
      • Toriyama S
      • Kawano H
      • Ohsaka S
      Scoring system for the preoperative evaluation of metastatic spine tumor prognosis.
      ,
      • Harrington KD
      Orthopedic surgical management of skeletal complications of malignancy.
      ,
      • White AP
      • Kwon BK
      • Lindskog DM
      • Friedlaender GE
      • Grauer JN
      Metastatic disease of the spine.
      ]. Given recent advances in surgical and radiation techniques, this 3-month threshold requires further evaluation. Rapid and sustained improvement in quality of life after spinal surgery for metastasis has been reported in numerous recent series [
      • Hansen-Algenstaedt N
      • Kwan MK
      • Algenstaedt P
      • Chiu CK
      • Viezens L
      • Chan TS
      • et al.
      Comparison between minimally invasive surgery and conventional open surgery for patients with spinal metastasis: a prospective propensity score-matched study.
      ,
      • Hikata T
      • Isogai N
      • Shiono Y
      • Funao H
      • Okada E
      • Fujita N
      • et al.
      A retrospective cohort study comparing the safety and efficacy of minimally invasive versus open surgical techniques in the treatment of spinal metastases.
      ,
      • Miscusi M
      • Polli FM
      • Forcato S
      • Ricciardi L
      • Frati A
      • Cimatti M
      • et al.
      Comparison of minimally invasive surgery with standard open surgery for vertebral thoracic metastases causing acute myelopathy in patients with short- or mid-term life expectancy: surgical technique and early clinical results.
      ,
      • Rao PJ
      • Thayaparan GK
      • Fairhall JM
      • Mobbs RJ
      Minimally invasive percutaneous fixation techniques for metastatic spinal disease.
      ,
      • Zuckerman SL
      • Laufer I
      • Sahgal A
      • Yamada YJ
      • Schmidt MH
      • Chou D
      • et al.
      When less is more: the indications for MIS techniques and separation surgery in metastatic spine disease.
      ]. Some authors have recently suggested that a life expectancy of 2 months or even less, would still justify potential surgical benefits of improved quality of life over morbidity and complications [
      • Hansen-Algenstaedt N
      • Kwan MK
      • Algenstaedt P
      • Chiu CK
      • Viezens L
      • Chan TS
      • et al.
      Comparison between minimally invasive surgery and conventional open surgery for patients with spinal metastasis: a prospective propensity score-matched study.
      ,
      • Hikata T
      • Isogai N
      • Shiono Y
      • Funao H
      • Okada E
      • Fujita N
      • et al.
      A retrospective cohort study comparing the safety and efficacy of minimally invasive versus open surgical techniques in the treatment of spinal metastases.
      ,
      • Miscusi M
      • Polli FM
      • Forcato S
      • Ricciardi L
      • Frati A
      • Cimatti M
      • et al.
      Comparison of minimally invasive surgery with standard open surgery for vertebral thoracic metastases causing acute myelopathy in patients with short- or mid-term life expectancy: surgical technique and early clinical results.
      ]. Surgical decision making, in conjunction with patient preference, must be informed by accurate life expectancy estimates, anticipated complications, and potential for postoperative improvement in quality of life. Despite recent improvement in this field [
      • Goodwin CR
      • Schoenfeld AJ
      • Abu-Bonsrah NA
      • Garzon-Muvdi T
      • Sankey EW
      • Harris MB
      • et al.
      Reliability of a spinal metastasis prognostic score to model 1-year survival.
      ,
      • Schoenfeld AJ
      • Leonard DA
      • Saadat E
      • Bono CM
      • Harris MB
      • Ferrone ML
      Predictors of 30- and 90-day survival following surgical intervention for spinal metastases: a prognostic study conducted at four academic centers.
      ], the ability of the clinician to accurately predict life expectancy in patients with metastatic cancer remains challenging, particularly in an urgent setting with incomplete information. Sacropenia, as assessed by a relatively practical tool (L3-TPA/VBA), has the potential to improve risk prediction and informed consent. The Bollen Prognostic Scale was specifically designed to predict mortality and not AEs or quality of life improvement. We confirmed this fact, demonstrating a statistically significant association of the Bollen Scale with survival but not AEs in our study population. The Bollen Prognostic Scale does not capture the impact of postoperative complications. Moreover, in the emergency setting when the primary tumor site is often unknown, the Bollen Scale cannot be applied.
      Sarcopenia is associated with functional decline and is a manifestation of frailty in the general population. A growing body of literature, spanning various surgical populations, confirms its association with poor clinical outcome [
      • Hasselager R
      • Gogenur I
      Core muscle size assessed by perioperative abdominal CT scan is related to mortality, postoperative complications, and hospitalization after major abdominal surgery: a systematic review.
      ,
      • Lee JS
      • He K
      • Harbaugh CM
      • Schaubel DE
      • Sonnenday CJ
      • Wang SC
      • et al.
      Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair.
      ,
      • Miyamoto Y
      • Baba Y
      • Sakamoto Y
      • Ohuchi M
      • Tokunaga R
      • Kurashige J
      • et al.
      Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer.
      ,
      • Tan BH
      • Birdsell LA
      • Martin L
      • Baracos VE
      • Fearon KC
      Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer.
      ,
      • Zargar H
      • Almassi N
      • Kovac E
      • Ercole C
      • Remer E
      • Rini B
      • et al.
      Change in psoas muscle volume as a predictor of outcomes in patients treated with chemotherapy and radical cystectomy for muscle-invasive bladder cancer.
      ,
      • Cloney M
      • D'Amico R
      • Lebovic J
      • Nazarian M
      • Zacharia BE
      • Sisti MB
      • et al.
      Frailty in geriatric glioblastoma patients: a predictor of operative morbidity and outcome.
      ]. Previous reports on nononcological spinal surgery populations have shown that morphometric analysis of the psoas could predict complications [
      • Zakaria HM
      • Schultz L
      • Mossa-Basha F
      • Griffith B
      • Chang V
      Morphometrics as a predictor of perioperative morbidity after lumbar spine surgery.
      ] and mortality [
      • Zakaria HM
      • Basheer A
      • Boyce-Fappiano D
      • Elibe E
      • Schultz L
      • Lee I
      • et al.
      Application of morphometric analysis to patients with lung cancer metastasis to the spine: a clinical study.
      ].
      Our results provide new, clinically relevant information to the existing literature regarding the role of sarcopenia on predicting early postoperative outcomes. Gakhar et al. and Zhakaria et al. have previously reported decreased survival with lower psoas size in patients with spinal metastasis [
      • Gakhar H
      • Dhillon A
      • Blackwell J
      • Hussain K
      • Bommireddy R
      • Klezl Z
      • et al.
      Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression.
      ,
      • Zakaria HM
      • Basheer A
      • Boyce-Fappiano D
      • Elibe E
      • Schultz L
      • Lee I
      • et al.
      Application of morphometric analysis to patients with lung cancer metastasis to the spine: a clinical study.
      ]. In contrast to our study, Zakaria et al. did not examine patients who underwent surgical intervention, but rather those treated with radiation therapy only. Using a measurement technique similar to this study, Gakhar et al. demonstrated an increased 1-year mortality in 86 metastatic spine patients who had the lowest quartile of psoas muscle mass. Our study adds further to these studies as we purposely included medium term survival endpoints (1 and 3 month) given this urgent surgical population. We propose the L3-TPA/VBA ratio as a practical, clinically useful tool to predict one and 3-month survival, with the lowest quartile of L3-TPA/VBA ratio (<0.81) significantly predictive of early mortality and complications.
      Previous studies have differed in their methodology for measuring sarcopenia and frailty. Normalizing psoas area to patient height is the most commonly utilized method to measure sarcopenia and account for patient morphology. Accurate measurement of patient height can be challenging in patients confined to bed and can vary with spinal fracture or deformity. Accordingly, we elected to normalize the psoas area using the area of the third lumbar vertebra (L3-TPA/VBA), as this does not require patient mobilization or rely on patient's memory of his own height. Furthermore, this measurement is practical and simultaneously available on the same CT scan slice as the psoas muscle area. This technique has previously been used in the metastatic spine population and has shown good correlation with the conventional NTPA measures (r=0.77; p<0.0001) [
      • Gakhar H
      • Dhillon A
      • Blackwell J
      • Hussain K
      • Bommireddy R
      • Klezl Z
      • et al.
      Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression.
      ,
      • Zakaria HM
      • Basheer A
      • Boyce-Fappiano D
      • Elibe E
      • Schultz L
      • Lee I
      • et al.
      Application of morphometric analysis to patients with lung cancer metastasis to the spine: a clinical study.
      ].
      Most frailty measurement tools are derived from the theory of accumulating deficit popularized by Rockwood et al. [
      • Rockwood K
      • Song X
      • MacKnight C
      • Bergman H
      • Hogan DB
      • McDowell I
      • et al.
      A global clinical measure of fitness and frailty in elderly people.
      ]. Frailty indexes, like mFI and MSTFI, were designed to identify patients at risk of AE using large nationwide surgical databases and previous studies showed correlation between mFI and postoperative outcomes in various surgical populations [
      • Cloney M
      • D'Amico R
      • Lebovic J
      • Nazarian M
      • Zacharia BE
      • Sisti MB
      • et al.
      Frailty in geriatric glioblastoma patients: a predictor of operative morbidity and outcome.
      ]. Unlike mFI, MSTFI was not extensively studied in literature but it was specifically designed for the metastatic spinal patient population. For the above reasons, we decided to study both MSTFI and mFI.
      We found that the use of mFI might be altered by a ceiling effect in the metastatic spinal population. Using a cut-off of 0.21 for the mFI, only, 14.8% of our population was categorized as frail. Comparatively, 43.5% of our patients were classified as moderately or severely frail when using MSTFI, suggesting that this frailty measurement is more sensitive and specific to the metastatic spine disease population. Moreover, the clinical use of both these indices might be limited in the emergency setting by the need for extensive medical chart data abstraction for their calculation.
      Interestingly, we found no correlation between surgical invasiveness measured with The Spine Surgery Invasiveness Index (SSII) and outcome in this population. SSII was designed to quantify surgical invasiveness in the spinal surgery population [
      • Mirza SK
      • Deyo RA
      • Heagerty PJ
      • Konodi MA
      • Lee LA
      • Turner JA
      • et al.
      Development of an index to characterize the "invasiveness" of spine surgery: validation by comparison to blood loss and operative time.
      ]. Previous authors have reported a relation between SSII and the occurrence of postop adverse events in trauma and degenerative spine populations [
      • Charest-Morin R
      • Street J
      • Zhang H
      • Roughead T
      • Ailon T
      • Boyd M
      • et al.
      Frailty and sarcopenia do not predict adverse events in an elderly population undergoing non-complex primary elective surgery for degenerative conditions of the lumbar spine.
      ,
      • Bourassa-Moreau E
      • Mac-Thiong JM
      • Ehrmann Feldman D
      • Thompson C
      • Parent S
      Complications in acute phase hospitalization of traumatic spinal cord injury: does surgical timing matter?.
      ]. Our findings suggested that surgical invasiveness may not play a clinically significant role in this metastatic spinal population, at least not relative to the other putative clinical predictors. Because of the observational nature of our study, an allocation bias of less invasive surgical strategies for higher-risk patients may have minimized any impact of SSII on outcome.
      In this study, survival was calculated based from both the day of admission (doADM) and the day of the CT-Scan (doCT-S) from which psoas area was measured. Using admission as the reference point is most commonly used and helps frame the discussion with patients and their families. However, using the doCT-S acquisition reflects more the biological effect of L3-TPA/VBA as it is likely to change with time especially in cancer population [
      • Daly LE
      • Ní Bhuachalla ÉB
      • Power DG
      • Cushen SJ
      • James K
      • Ryan AM
      Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer.
      ,
      • Rutten IJ
      • van Dijk DP
      • Kruitwagen RF
      • Beets-Tan RG
      • Olde Damink SW
      • van Gorp T
      Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients.
      ]. This is in keeping with our finding of a stronger correlation between L3-TPA/VBA and survival when using doCT-S rather than doADM. Ideally, a CT scan, allowing psoas measurement, would be performed on the doADM, thus allowing optimal use of this clinically important tool. The results from our study support the use of L3-TPA/VBA as a surrogate of sarcopenia, and a readily available, easily measureable adjunct to help with the complex clinical decision making in the metastatic spine population.

      Limitations

      A limitation common to studies examining sarcopenia is the lack of a universally accepted definition. Various cut-offs have been proposed in different surgical populations including general surgery, gynecology, and urology. These cut-offs were defined using tertiles or quartiles, with no comment on the normality of sarcopenia in their population, thus limiting the external validity of their findings. Ideally, a cut-off should be determined for a specific clinical purpose such as surgical indication, invasiveness of surgery or prognostication. Ultimately, as part of an informed consent, some patients can still choose to undergo surgery despite knowing the risk of AE or early mortality. We found the greatest increment in mortality between the first and second quartile psoas (cut-off being roughly 0.81) but we do believe this cut-off should be verified in large prospective studies before being applied for clinical decision.
      We may have introduced selection bias as 31 patients were excluded from the study because they did not have adequate preoperative imaging including the L3 region.
      Lastly, the number of patients included in our study was also relatively small and limited to a single center, therefore our results might not be generalizable to other centers. Our study may have been underpowered to detect relationships between the various predictor variables and outcomes, including the SII.

      Conclusions

      Sarcopenia, as measured by L3-TPA/VBA, predicted both early mortality and acute care adverse events and patients undergoing urgent surgery for spinal metastases. Although the MSTFI and Bollen scale predicted early mortality in our population, we did not find a significant relationship with other adverse events. Sarcopenia, as measured by L3-TPA/VBA, is practical, readily available, and can inform surgical decision-making prior to urgent surgery where prognostic information may be incomplete. Further research should focus on validating this predictive tool in surgical patients with metastatic disease of the spine.

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