Retroperitoneal sarcomas (RPS) are soft tissue tumours of mesenchymal origin accounting for approximately 15% of all sarcomas and less than 1% of all tumour malignancy.1,2,3 Most patients develop large tumour mass before diagnosis is clinically confirmed. Imaging techniques, CT and MRI are primarily used in clinical evaluation of RPS.1,4 Surgical resection with removal of all gross disease is the cornerstone of curative therapy and optimal results are achieved with
Body composition changes are related to nutrition status and associated with perioperative outcome and influence management of surgical oncology patients.15 Ongoing catabolic processes, systemic inflammation, as well as decreased protein synthesis, as part of often presented cancer-associated cachexia, together contribute to loss of lean body mass and pose a risk of malnutrition in sarcoma patients.16,17,18 Sarcopenia is a clinical syndrome in which involuntary loss of skeletal muscle mass and function is progressive and generalized, together or without increased fat mass.19,20 Another clinically important body composition abnormality, myosteatosis, is characterized by excess accumulation of adipose tissue within muscle, resulting in impaired muscle strength and physical ability, as well as increased frailty.21,22 Recent studies demonstrated that both sarcopenia and myosteatosis pose a greater risk for postoperative complications and decrease overall survival (OS) in a variety of different cancers, including soft tissue sarcomas.22,23,24,25,26,27 Visceral obesity (VO) is the fat accumulation in visceral adipose tissue and serves as a clinical marker for adiposopathy.28 Number of recent studies reported that VO is more reliable clinical marker for predicting outcome than traditional view on obesity defined by BMI.29,30,31,32,33 The useful predictor of VO is visceral-to-subcutaneous adipose tissue area ratio (VSR), and high VSR is associated with poor oncologic outcome.34,35,36,37 Also, another body composition abnormality, the new concept of sarcopenic obesity (SO), a combination of excess adiposity and sarcopenia, seems to have powerful negative prognostic impact in oncology treatment and is gaining increased attention in cancer research.38,39 Loss of muscle mass or myopenia is a critical determinant of sarcopenia.
CT has been shown to be a precise and feasible method to evaluate body composition parameters.40,41,42,43 There is a lack of literature data regarding the impact of body composition on postoperative and oncologic outcome in patients operated on for primary RPS.
The aim of our study is to investigate the impact of low muscle mass or myopenia, myosteatosis, visceral obesity and cancer cachexia on OS, local recurrence-free survival (LRFS) and postoperative morbidity in patients operated for primary localized RPS. Additionally, we aimed to investigate the predictive value of preoperative body composition parameters for OS, LRFS and postoperative morbidity.
Retrospective study was conducted on patients operated on for primary RPS at Department of Surgical Oncology at the Institute of Oncology Ljubljana between September 1999 and June 2020 (Figure 1). A total of 58 patients met the inclusion criteria, 24 females (41.4%) and 34 males (58.6%). The Slovenian National Medical Ethical Committee (decision number: 0120-530/2020/3), Institutional Review Board (ERID-KSOPKR-0081/2020) and Institutional Ethical Committee (ERIDEK-0079/2020) approved the study. Due to the retrospective nature of the study the need to obtain informed consent from participants was waived.
Patient's histories including anesthesiologic pre-operative reports, operative reports, hospital records, and follow-up data were reviewed. Clinical and pathological data were collected (Figure 1). Postoperative complications were evaluated in accordance with Clavien–Dindo classification.44 Tumour features of interest were as follows: histopathological diagnosis, stage (according to American Joint Committee on Cancer [AJCC] 8th Edition), grade (according to National Federation of Centers for the Fight Against Cancer grading system)45 and tumour size (largest diameter value). Resection quality was recorded as either complete (R0), incomplete (R1) with microscopic involvement of resection margins or macroscopic residual tumour (R2).
The assessment of body composition was conducted using images from CT scans taken within 30 days preoperatively at the level of the third lumbar vertebra using the “Automated Body Composition Analyzer using Computed tomography image Segmentation” (ABACS) software.46 This method uses predefined CT Hounsfield units (HU) values to recognize different tissues. The CT HU thresholds were 29 to 150 for skeletal muscles, 190 to 30 for subcutaneous adipose tissue, and 150 to 50 for visceral adipose tissue. The following body composition parameters were measured: total cross-sectional skeletal muscle area (SMA, cm2), subcutaneous adipose tissue area (SAT, cm2) and visceral adipose tissue area (VAT, cm2). After normalization by patient's height (m2), we used these parameters as lumbar skeletal muscle index (SMI, cm2/m2), subcutaneous adipose tissue index (SATI, cm2/m2), and visceral adipose tissue index (VATI, cm2/m2). VSR was calculated by dividing VAT by SAT. To assess the muscle density and myosteatosis, skeletal muscle radiation attenuation (MRA) has also been recorded in HUs. All measurements were performed by experienced researcher, accredited for complex image analysis and segmentation techniques. Additionally, we used previously reported and validated equations to calculate appendicular skeletal muscle index (ASMI), lean body mass (LBM) and fat mass (FM)26,29,43,47:
Based on a single abdominal CT image per patient, LBM and FM properly reflect appropriate dual-energy X-ray absorptiometry (DXA) derived whole-body fat-free mass (FFM) and whole-body fat mass (FM), respectively.
Myopenia was defined based on the new recommendations of The European Working Group on Sarcopenia in Older People (EWGSOP2), as follows: SMI < 43 cm2/m2 for men with BMI < 25, SMI < 53 cm2/m2 for men with BMI ≥ 25, and SMI < 41 cm2/m2 for women.48
Muscle mass in patients with obesity was assessed according to The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) consensus report for sarcopenic obesity.39 Previously reported diagnostic criteria for visceral obesity were applied: VAT > 163.8 cm2 for men and VAT > 80.1 cm2 for women.29,39,47
Preoperative cancer cachexia was defined using Fearon
In order to establish optimal cut-off values for SMI, VATI, SATI, VSR and MRA which would best reflect our study cohort in relationship to defined outcome (maximum OS), we performed optimal stratification analysis based on maximally selected rank statistics using
Final survival follow-up time was set as last follow-up date in the study period or the event of death. OS was defined as time between the date of the operation and date of death from any cause or last follow-up. LRFS was defined as the time interval between operation date and date of first documented local progression, and instances involving deaths without evidence of disease and the occurrence of distant metastases considered as competing events. Survival curves were estimated using Kaplan-Meier method. Log-rank test, linear regression and Cox proportional hazard regression models were used to analyse the relationship between clinicopathological parameters and survival. Hosmer-Lemeshow test assessed the prediction accuracy (goodness of fit) of regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained.
In addition to body composition parameters, following known prognostic factors or other clinical features were considered: age, gender, American Society of Anesthesiologists (ASA) classification, Albumin level (g/dL), C-reactive protein (mg/L), neutrophil-to-lymphocyte ratio (NLR), preoperative radiotherapy, tumour size (cm), and intraoperative blood loss (ml). Results were statistically significant if two-sided p value < 0.05 was achieved. R statistical software (version 4.2.1, R core Team) was used.
Out of 89 primary localized RPS cases, clinical and pathological characteristics and preoperative abdominal CT scans technically adequate for analysis were available for 58 patients, representing the final study cohort (Figure 1). The demographic and clinical characteristics of the patients are provided in Table 1. In the cohort, 34 (58.6%) were males and 24 (41.4%) were females. Median age at diagnosis was 61.0 (46.0–67.0). Loss of muscle mass according to EWGSOP2 criteria, was present in 19 patients (32.8%). Applying our cut-off values for low SMI, comparable number of myopenic patients was detected, 12 males (66.7%) and 6 females (33.33%). Significant difference between myopenic and non-myopenic group was detected in tumour size (median 26
Clinical characteristics of study population
Age, years | 61.0 (46.0 – 67.0) |
Gender | |
Male | 34 (58.6%) |
Female | 24 (41.4%) |
ASA grade | |
1 | 9 (16%) |
2 | 30 (52%) |
3 | 16 (28%) |
4 | 3 (5.2%) |
Baseline albumin, g/L | 41.0 (34.2 – 45.0) |
Baseline C-reactive protein, mg/L | 13.5 (2.0 – 66.5) |
Neutrophil-lymphocyte ratio | 3.3 (2.1 – 4.7) |
Body Mass Index, kg/m2 | 26.0 (24.7 – 29.7) |
Nutritional team support before operation | 28(48.3%) |
Skeletal Muscle Area, cm2 | 45.5 (115.9 – 170.1) |
Visceral Fat Area, cm2 | 104.5 (53.6 – 168.7) |
Subcutaneous Adipose Tissue Area, cm2 | 167.9 (127.9 – 231.6) |
Total Fat Area, cm2 | 23.6 (19.8 – 29.1) |
Total Body Fat, % | 30.6 (26.8 – 32.4) |
Lean Body Mass, kg | 52.7 (50.0 – 57.2) |
Skeletal Muscle Index, cm2/m2 | 50.2 (44.0 – 55.6) |
Appendicular Skeletal Muscle Index, cm2/m2 | 6.70 (6.00 – 7.3) |
Myopenia based on estimated cut-off value for SMIa | 18 (31.0%) |
Myopenia based on EWGSOP2 criteria for SMI | 19 (32.8%) |
Cancer cachexia | 13 (22.4%) |
Visceral obesity | 21 (36.2%) |
Myopenic obesity | 4 (6.9%) |
Myosteatosisa | 37 (63.7%) |
Postoperative (90 day) complication rate | 37 (64%) |
Abdominal complication | 24 (41%) |
Systemic complication | 17 (29%) |
Abdominal and systemic complications | 5 (9.0%) |
Clavien-Dindo > IIIa | |
Yes | 17 (29%) |
No | 41 (71%) |
Comprehensive Complication Index | 20.92 (0.0–32.55) |
Histologic type | |
Liposarcoma | 35 (60%) |
Leiomyosarcoma | 9 (16%) |
Pleomorphic sarcoma | 1 (1.7%) |
Other | 13 (22%) |
Tumour size, cm | 20 (11–30) |
FNCLCC grade | |
1 | 15 (26%) |
2 | 11 (19%) |
3 | 23 (40%) |
Unknown | 9 (16%) |
Stage AJCC (8th edition) | |
1A | 1 (1.7%) |
1B | 23 (40%) |
3A | 6 (10%) |
3B | 28 (48%) |
Completeness of surgical resection | |
R0 | 47 (81%) |
R1/R2 | 11 (19%) |
AJCC = The American Joint Committee on Cancer; ASA = American Society of Anesthesiologists classification; EWGSOP2 = The European Working Group on Sarcopenia in Older People; FNCLCC = Fédération Nationale des Centres de Lutte Contre Le Cancer
Summary for continuous variables is presented as median (interquartile range) and the statistical test is Kruskal-Wallis/Mann-Whitney;
cut-off values displayed in Table 3
Comparison of clinical and body composition parameters between myopenic and non-myopenic patients (EGSWOP2 criteria)
Age, years | Median (IQR) | 66.0 (50.5–71.5) | 61.0 (46.0–64.8) | 0.236 |
Gender | Male | 11(57.9) | 23 (60.5) | 1 |
Female | 8(42.1) | 15 (39.5) | ||
ASA Grade, 2–3 |
1 | 3 (15.8) | 6 (15.8) | 1 |
2–3 | 16 (84.2) | 32 84.2) | ||
FNCLCC Grade | 1 | 5 (29.4) | 10 (32.3) | 0.547 |
2 | 5 (29.4) | 5 (16.1) | ||
3 | 7 (41.2) | 16 (51.6) | ||
(Missing) | 7 (18.4) | 2 (10.5) | ||
Tumour size, cm | Median (IQR) | 26.0 (20.5–34.0) | 17.5 (10.0–24.8) | 0.005 |
Clavien-Dindo > IIIa | Yes | 3 (15.8) | 14 (36.8) | 0.183 |
No | 16 (84.2) | 24 (63.2) | ||
Neutrophil-lymphocyte ratio | Median (IQR) | 3.9 (2.4–4.7) | 3.0 (2.1–4.7) | 0.504 |
Baseline albumin, g/L | Median (IQR) | 40.0 (32.0–42.5) | 43.0 (35.0–45.8) | 0.232 |
Baseline C-reactive protein, mg/L | Median (IQR) | 44.0 (7.5–99.5) | 6.0 (2.0–45.0) | 0.088 |
Haemoglobin level, g/L | Median (IQR) | 128.0 (101.5–136.5) | 132.5 (115.2–145.8) | 0.141 |
Preoperative radiotherapy | No | 19 (100.0) | 37 (97.4) | 1 |
Yes | 0 (0.0) | 1 (2.6) | ||
Resection status | R0 | 17 (89.5) | 29 (76.3) | 0.406 |
R1 | 2 (10.5) | 9 (23.7) | ||
Intraoperative blood loss, ml | Median (IQR) | 1300.0 (425.0–4100.0) | 1350.0 (500.0–2075.0) | 0.78 |
Stage AJCC, 8th edition | 1A–1B | 7 (36.8) | 17 (44.7) | 0.776 |
3A–3B | 12 (63.2) | 21 (55.3) | ||
Histology subtype | Pleomorphic | 1 (5.3) | 0 (0.0) | 0.184 |
Liposarcoma | 14 (73.7) | 21 (55.3) | ||
Leiomyosarcoma | 2 (10.5) | 6 (15.8) | ||
Other | 2 (10.5) | 11 (28.9) | ||
Nutrition team before surgery | Yes | 12 (63.2) | 16 (42.1) | 0.223 |
No | 7 (36.8) | 22 (57.9) | ||
Length of hospital stay, days | Median (IQR) | 20.0 (11.0–28.8) | 15.0 (11.5–27.0) | 0.593 |
Visceral obesity | Yes | 4 (21.1) | 16 (42.1) | 0.202 |
No | 15 (78.9) | 22 (57.9) | ||
Myosteatosis | Yes | 16 (84.2) | 21 (56.8) | 0.079 |
No | 3 (15.8) | 16 (43.2) | ||
Cancer cachexia | No | 12 (63.2) | 31 (83.8) | 0.163 |
Yes | 7 (36.8) | 6 (16.2) | ||
Body Mass Index, kg/m2 | Median (IQR) | 25.7 (23.3–27.2) | 26.9 (24.8–30.9) | 0.071 |
Skeletal Muscle Area, HU | Median (IQR) | 115.8 (106.5–153.3) | 149.9 (130.6–177.1) | 0.019 |
Skeletal Muscle Index, cm2/m2 | Median (IQR) | 41.0 (38.3–46.8) | 53.5 (46.2–58.8) | < 0.001 |
Muscle Radiation Attenuation, HU | Median (IQR) | 35.6 (31.8–43.2) | 38.1 (29.9–42.2) | 0.959 |
Subcutaneous Adipose Tissue Area, cm2 | Median (IQR) | 156.4 (103.2–194.4) | 185.4 (131.4–254.1) | 0.078 |
Visceral Adipose Tissue Area, cm2 | Median (IQR) | 64.6 (38.1–131.6) | 125.5 (66.1–201.7) | 0.07 |
Visceral-to-subcutaneous adipose tissue area ratio | Median (IQR) | 0.5 (0.2–0.9) | 0.8 (0.3–1.1) | 0.393 |
Body fat, % | Median (IQR) | 28.3 (21.3–31.6) | 31.1 (28.1–33.3) | 0.024 |
Lean Body Mass, kg | Median (IQR) | 52.5 (50.4–57.7) | 52.8 (49.8–56.4) | 0.684 |
Subcutaneous Adipose Tissue Index, cm2/m2 | Median (IQR) | 46.8 (30.6–67.2) | 64.6(43.9–95.0) | 0.048 |
Visceral Adipose Tissue Index, cm2/m2 | Median (IQR) | 20.6 (13.2–43.8) | 42.3 (24.2–63.6) | 0.025 |
Summary for continuous variables is median (interquartile range) and the statistical test is Kruskal-Wallis/Mann-Whitney;
Median (IQR); n (%);
AJCC =The American Joint Committee on Cancer; ASA = American Society of Anesthesiologists; EGSWOP2 = The European Working Group on Sarcopenia in Older People; FNCLCC = Fédération Nationale des Centres de Lutte Contre Le Cancer; HU = Hounsfield units
Results of optimal stratification analysis for body composition parameters
49.21 | 49.21 | 61.38 | 25.55 | 49.23 | 86.89 | 0.26 | 47.41 | |||
49.90 | 50.64 | 35.88 |
BMI = body mass index; HU = Hounsfield Unit;
adjusted for gender and BMI;
adjusted for gender only;
cut-off determined on the level of whole cohort, not stratified for BMI nor gender;
adjusted for BMI only.
Males had significantly higher mean values of SMA (163.7
The results of optimal stratification analysis for finding cut-off values for SMI, VATI, SATI, VSR and MRA are presented in Table 3 and Supplementaly Figures 1–4.
In the cohort, median follow up time was 116 months, with 5-year OS of 66.8% (95% CI 53.9–82.7). The result of univariate analysis of OS is presented in Supplementaly Table 2. Of the nutritional and body composition features, myopenia (HR 3.18, 95% CI 1.11–8.56, p = 0.020), cancer cachexia (HR 6.07, 95% CI 2.24–16.46, p < 0.001), high VSR (HR 4.32, p = 0.043) and low SATI (HR 4.91, 95% CI 1.11–21.65, p = 0.02) were associated with elevated risk for overall mortality. SMI and BMI had small protective impact on OS in univariate analysis (HR 0.95, p = 0.040 and HR 0.83, p = 0.036, respectively). Of the known prognostic factors, preoperative levels of albumin, CRP, NLR, and AJCC stage were associated with OS. Major postoperative morbidity (CD > IIIa) was significantly correlated with shorter OS (HR 3.16, 95% CI, 1.24–8.04, p = 0.016). Multivariate analysis of OS confirmed the significance of myopenia (myopenic vs. non-myopenic: adjusted HR 6.5, p = 0.032), cancer cachexia (cachectic vs. non-cachectic: adjusted HR 13.7, p = 0.004) and high SATI (adjusted HR 7.00, p = 0.057). Major postoperative morbidity, NLR and albumin level also remained significant in multivariate OS analysis (Figure 2 A–E).
The 5-year LRFS for whole study cohort was 77.6% (95% CI, 65.2–92). In univariate analysis among all body composition parameters, only SMI and SATI (low
We performed univariate and multivariate risk factor analysis to evaluate factors associated with postoperative morbidity, intrahospital length of stay (LOS) and major postoperative complications.
The median postoperative LOS was 18 days (IQR: 11.25–28.75). In univariate analysis, higher ASA grade (2–3
Summary of univariate and multivariate analysis of association between body composition and outcome following surgery for primary RPS
Myopenia, yes |
1.34 (0.38–5.54) | 0.664 | - | - | 0.32 (0.07–1.18) | 0.112 | - | - | 3.11 (0.85–15.08) | 0.112 | - | - |
Visceral obesity, yes |
2.54 (0.68–12.40) | 0.196 | - | - | 0.65 (0.18–2.13) | 0.49 | - | - | 3.61 (1.09–14.44) | 0.047 | - | - |
Myopenic obesity, yes |
0.01 (0.00–0.001) | 0.993 | - | - | 20090605.83 (0.00–NA) | 0.993 | - | - | 279.10 (0.00–NA) | 0.993 | - | - |
Myosteatosis, yes |
1.39 (0.39–5.76) | 0.626 | - | - | 2.17 (0.58–10.58) | 0.282 | - | - | 5.05 (1.39–24.41) | 0.023 | 4.63 (1.03–28.42) | 0.063 |
Cancer cachexia, yes |
0.68 (0.18–2.94) | 0.585 | - | - | 2.83 (0.76–10.59) | 0.117 | - | - | 0.95 (0.27–3.60) | 0.935 | - | - |
Body mass index, kg/m2 | 1.00 (0.89–1.14) | 0.992 | - | - | 0.94 (0.81–1.06) | 0.351 | - | - | 0.95 (0.27–3.60) | 0.935 | - | - |
Skeletal Muscle Area, HU | 1.00 (0.99–1.02) | 0.869 | - | - | 1.00 (0.98–1.01) | 0.679 | - | - | 1.00 (0.99–1.02) | 0.681 | - | - |
Skeletal Muscle Index, cm2/m2 | 1.00 (0.95–1.07) | 0.88 | - | - | 1.00 (0.95–1.06) | 0.909 | - | - | 1.04 (0.98–1.10) | 0.230 | - | - |
Muscle Radiation Attenuation, HU | 0.98 (0.92–1.04) | 0.526 | - | - | 0.99 (0.93–1.05) | 0.775 | - | - | 0.94 (0.88–1.00) | 0.076 | - | - |
SAT, cm2 | 1.00 (0.99–1.00) | 0.336 | - | - | 1.00 (0.99–1.00) | 0.48 | - | - | 1.00 (0.99–1.01) | 0.866 | - | - |
VAT, cm2 | 1.00 (1.00–1.01) | 0.769 | - | - | 1.00 (0.99–1.00) | 0.622 | - | - | 1.00 (1.00–1.01) | 0.205 | - | - |
VSR | 1.55 (0.53–5.51) | 0.456 | - | - | 1.09 (0.39–2.861) | 0.861 | - | - | 1.72 (0.66–5.19) | 0.292 | - | - |
High VSRb, yes |
2.50 (0.63–9.52) | 0.179 | - | - | 2.75 (0.63–19.26) | 0.224 | - | - | 6.19 (1.69–26.52) | 0.008 | 5.05 (1.08–29.74) | 0.05 |
Body fat, % | 0.96 (0.87–1.05) | 0.380 | - | - | 1.00 (0.92–1.09) | 0.962 | - | - | 1.00 (0.93–1.09) | 0.912 | - | - |
Lean Body Mass, kg | 1.01 (0.96–1.07) | 0.765 | - | - | 1.02 (0.97–1.08) | 0.381 | - | - | 1.02 (0.97–1.08) | 0.381 | - | - |
SATI, cm2/m2 | 0.99 (0.97–1.01) | 0.279 | - | - | 0.99 (0.97–1.01) | 0.344 | - | - | 1.00 (0.99–1.02) | 0.794 | - | - |
VATI, cm2/m2 | 1.00 (0.99–1.02) | 0.625 | - | - | 1.00 (0.98–1.01) | 0.706 | - | - | 1.01 (1.00–1.04) | 0.122 | - | - |
High SATIc, yes |
1.80 (0.52–6.25) | 0.346 | - | - | 0.90 (0.26–2.93) | 0.863 | - | - | 1.50 (0.49–4.81) | 0.481 | - | - |
High VATId, yes |
0.49 (0.10–1.87) | 0.327 | - | - | 0.38 (0.08–1.44) | 0.184 | - | - | 2.83 (0.84–11.45) | 0.111 | - | - |
OR = Odds Ratio; SAT = Subcutaneous Adipose Tissue Area; SATI = Subcutaneous Adipose Tissue Index; VAT = Visceral Adipose Tissue Area; VATI = Visceral Adipose Tissue Index; VSR = Visceral-to-subcutaneous adipose tissue area ratio;
assessed by the European Working Group on Sarcopenia in Older People revised criteria from 2018;
defined as VSR > 0.26;
defined as SATI > 49.23 for males and SATI > 86.89 for females;
defined as VATI > 61.38 for males and VATI > 25.55 for females
Only significant variables (p < 0.05) were included in multivariate analysis.
In univariate analysis of overall postoperative morbidity, the presence of myosteatosis (OR 5.05, p = 0.023), VO (OR 3.61, p = 0.047) and high VSR (OR 6.19, p = 0.008) were associated with significantly higher overall complication rate. Adjusted for other covariates in multivariate analysis, high VSR maintained significant impact (adjusted OR 5.05, p = 0.05). We omitted VO from multivariate analysis to avoid multicollinearity. Figure 3 (panels A–F) summarises our analysis of morbidity following surgery for primary RPS.
Our study provided new insight into the association between preoperative body composition and postoperative and oncologic outcome in primary RPS patients. We focused on evaluation of the significance of preoperative nutrition status-related syndromes. Furthermore, we examined the predictive value of SMI and MRA, measures of muscular quantity and quality, as well as, VATI, SATI and VSR, measures of adiposity, for possible clinical use in preoperative clinical assessment of patients diagnosed with this rare malignancy. To address the lack of literature and inconsistency in used body composition cut points, we used maximally selected rank statistics to defined cohort – specific cut point. This method incorporated follow-up time and time-to-event outcomes, dividing the patients into two groups with the most significant statistics between each other in term of survival.56
In our cohort, both myopenia and VO were associated with poorer OS. Patients with myopenia had 5-year OS of 33.7%, compared to significantly higher 78.3% 5-year OS for non-myopenic patients (p = 0.009). SMI predicted LRFS on univariate analysis and lost prognostic value in multivariate analysis.
These findings are in line with knowledge that sarcopenic surgical oncology patients are at greater risk for poor operative outcome because of underlying muscle mass loss which is an integral component of sarcopenia and also facilitates the impairment of muscle function and physical performance.57 Therefore we used the cut-off values for diagnosis of myopenia which are the component of diagnostic criteria and tools that define and characterize sarcopenia in EWGSOP2 Revised European Consensus.48 Our optimal fitting method analysis for establishing the cut-off value for defining low SMI (used for comparative and descriptive purposes) resulted in slightly different cut-off values: SMI < 49.21 cm2/m2 for males and females with BMI < 25, and SMI < 49.9 cm2/m2 for males with BMI ≥ 25 and SMI < 50.64 cm2/m2 for females with BMI ≥ 25. Both EWGSOP2 criteria for low SMI and our cut-off values were able to predict poor prognosis. It seems, that difference is generated because our cohort consisted of only patients with primary RPS with resectable disease rather than a heterogeneous cohort. We also found that SMI analysed as continuous variable was not able to predict poor outcome. This is another proof that in clinical practice SMI should be evaluated as body composition (myopenia) parameter defined with cut-off values below which the risk of poor prognosis is increased significantly, rather than discretional decrease.58
Several studies demonstrated the superior predictive value of myosteatosis to sarcopenia or myopenia for poor survival.59,60,61 Most of this data is founded on reports about patients operated on for gastrointestinal cancers. In our study cohort myosteatosis was also associated with greater overall complication rate (OR 5.05, 95% CI 1.39–24.41, p = 0.023) in univariate analysis, but it was not confirmed in multivariate analysis. Myosteatosis was not associated with OS, LRFS or postoperative outcome. However, recently a group of authors reported significant association between myosteatosis and major complication rate and OS in retroperitoneal and trunk soft tissue sarcoma.29 They used preoperative MRA as continuous variable to define myosteatosis, not providing any cut-off point for reference. We defined myosteatosis based on optimal cut point analysis for MRA, and determined cut-offs are comparable to most commonly used range of MRA cut-offs for myosteatosis.62
In order to evaluate obesity and the distribution of fat tissue, we calculated VAT, SAT and corresponding height-adjusted indexes VATI and SATI. We also considered BMI. Higher value of BMI (≥ 25) was not associated with oncologic or postoperative outcome. This is in line with number of studies suggesting that BMI is not reliable prognostic parameter for predicting perioperative outcome in cancer patients.63,64,65 Stratified for myopenia, comparison of the subgroups revealed that body fat and VATI were significantly higher in non-myopenic patients (median 31.1
The multivariate analysis demonstrated that, when assessed as a continuous variable, albumin levels (HR 0.9, 95% CI 0.81–0.98, p = 0.019) and NLR (HR 1.4, 95% CI 1.06–1.75, p = 0.015) were independently associated with overall survival. This finding underscores the pivotal role of these inflammatory biomarkers in clinical practice and management of surgical oncology patients. Our results align with previous findings.17,18,72,73,74,75,76,77 Furthermore, our observation suggests that hypoalbuminemia identifies a high-risk cohort that may derive greater benefits from enhanced nutritional support preoperatively. The omission of descriptive statistical analysis for serum albumin and NLR, in term of patients' outcome, limits the depth of our data exploration.
Our study had some limitations. It was a single center report including relatively small number of patients which might influence the power of drown conclusions. Another weakness was the fact that we didn't assess all comorbidities in our analyses, as they were considered negligible in patients with soft tissue sarcoma. However, since our Institution is the only referral sarcoma center in Slovenia, having population of 2.1 million, our study cohort consisted of unique set of primary RPS patients eligible for curative surgery. We reported the most distinguishable, cohort – specific, cut points for CT measured body composition (muscle and adipose tissue) parameters in regard to long term prognosis. And finally, providing a unique and new insight into the association between preoperative body composition and postoperative and oncologic outcome in primary RPS patients was the main strength of the study.
Patients with primary RPS are in a great risk for nutritional disorders for number of reasons such as: requirement for demanding abdominal surgery in their management, long preclinical history and tumour size.4,10,18,78,79 In our study cohort there was a high prevalence of myopenia (32.8%) and visceral obesity (36.2%). Myopenia, cancer cachexia and low SATI were strongly associated with poor OS. High VSR was strong independent predictor for overall postoperative morbidity. Additional prospective studies are required to substantiate the role of preoperative VSR as independent prognostic factor for postoperative survival. Our findings suggest that clinical nutrition interventions towards improving visceral adiposity and myopenia may benefit surgical and oncologic outcome in primary RPS patients.