Radiol Oncol 2024; 58(1): 110-123. doi: 10.2478/raon-2024-0013
110
research article
Influence of nutritional status and body 
composition on postoperative events and 
outcome in patients treated for primary 
localized retroperitoneal sarcoma
Manuel Ramanovic
1
, Marko Novak
2
, Andraz Perhavec
2,3
, Taja Jordan
3,4
, Karteek Popuri
5
, 
Nada Rotovnik Kozjek
3,6
 
1 
Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
2
 Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
3
 Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
4
 Department for Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
5 
Department of Computer Science, Memorial University of Newfoundland, Newfundland, Canada
6
 Department of Clinical Nutrition, Institute of Oncology Ljubljana, Ljubljana, Slovenia
Radiol Oncol 2024; 58(1): 110-123.
Received 26 July 2023 
Accepted 3 November 2023
Correspondence to: Manuel Ramanović, M.D., Biotechnical Faculty, University of Ljubljana, Jamnikarjeva ul. 101, 1000 Ljubljana, Slovenia. 
E-mail: mako_manuel1@yahoo.com 
Disclosure: No potential conflicts of interest were disclosed.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background. Retroperitoneal sarcomas (RPS) are rare tumours of mesenchymal origin, commonly presented as a 
large tumour mass at time of diagnosis. We investigated the impact of body composition on outcome in patients 
operated on for primary localized RPS. 
Patients and methods. We retrospectively analysed data for all patients operated on for primary RPS at our insti-
tution between 1999 and 2020. Preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue 
area (VAT and SAT) and muscle radiation attenuation (MRA) were calculated using computed tomography scans at 
the level of third lumbar vertebra. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were 
applied to define myopenia. Using maximum log-rank statistic method we determined the optimal cut-off values of 
body composition parameters. Myosteatosis was defined based on determined MRA cut-offs.
Results. In total 58 patient were eligible for the study. With a median follow-up of 116 months, the estimated 5-year 
overall survival (OS) and local-recurrence free survival (LRFS) were 66.8% and 77.6%, respectively. Patients with myope-
nia had significantly lower 5-year OS compared to non-myopenic (p = 0.009). Skeletal muscle index and subcutane-
ous adipose tissue index predicted LRFS on univariate analysis (p = 0.052 and p = 0.039, respectively). In multivariate 
analysis high visceral-to-subcutaneous adipose tissue area ratio (VSR) independently predicted higher postoperative 
complication rate (89.2% vs. 10.8%, p = 0.008). Myosteatosis was associated with higher postoperative morbidity.
Conclusions. Myopenia affected survival, but not postoperative outcome in RPS. Visceral obesity, VSR (> 0.26) and 
myosteatosis were associated with higher postoperative morbidity. VSR was better prognostic factor than VAT in RPS.
Key words: body composition; myopenia; cancer cachexia; myosteatosis; obesity; retroperitoneal sarcoma
Introduction
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.
1-3
 Most patients de-
velop large tumour mass before diagnosis is clini-
cally confirmed. Imaging techniques, CT and MRI 

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 111
are primarily used in clinical evaluation of RPS.
1,4
 
Surgical resection with removal of all gross dis-
ease is the cornerstone of curative therapy and 
optimal results are achieved with en bloc resection 
at the time of primary presentation.
4,5
 The role of 
radiation therapy and chemotherapy in manage-
ment of RPS is still under investigation. Following 
the STRASS trial and STREXIT study, it seems that 
preoperative radiotherapy might influence the lo-
cal control in liposarcoma (LPS) patients, while the 
evaluation of chemotherapy remains ongoing for 
high-grade LPS and leiomyosarcoma.
6-8
 There are 
no currently available data supporting the use of 
routine neoadjuvant or adjuvant chemotherapy for 
these patients.
1
 Optimal management is achieved 
in specialized sarcoma centres
4,9 
with multidis-
ciplinary approach.
10-13
 Institute of Oncology 
Ljubljana is the only referral sarcoma centre in 
Slovenia.
14
Body composition changes are related to nu-
trition status and associated with perioperative 
outcome and influence management of surgical 
oncology patients.
15
 Ongoing catabolic processes, 
systemic inflammation, as well as decreased pro-
tein 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.
16-18
 Sarcopenia is a clinical syn-
drome in which involuntary loss of skeletal mus-
cle mass and function is progressive and general-
ized, together or without increased fat mass.
19,20
 
Another clinically important body composition 
abnormality, myosteatosis, is characterized by ex-
cess accumulation of adipose tissue within muscle, 
resulting in impaired muscle strength and physi-
cal 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 tis-
sue sarcomas.
22-27
 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 tra-
ditional view on obesity defined by BMI.
29-33
 The 
useful predictor of VO is visceral-to-subcutaneous 
adipose tissue area ratio (VSR), and high VSR is 
associated with poor oncologic outcome.
34-37
 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 myope-
nia is a critical determinant of sarcopenia. 
CT has been shown to be a precise and feasi-
ble method to evaluate body composition parame-
ters.
40-43
 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 local-
ized RPS. Additionally, we aimed to investigate 
the predictive value of preoperative body compo-
sition parameters for OS, LRFS and postoperative 
morbidity.
Patients and methods
Study design and population
Retrospective study was conducted on patients op-
erated on for primary RPS at Department of Surgical 
Oncology at the Institute of Oncology Ljubljana be-
tween September 1999 and June 2020 (Figure 1). A 
total of 58 patients met the inclusion criteria, 24 fe-
males (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.
Clinical data collection
Patient’s histories including anesthesiologic pre-
operative reports, operative reports, hospital re-
cords, 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: his-
topathological 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 involve-
ment of resection margins or macroscopic residual 
tumour (R2).

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 112
Body composition assessment
The assessment of body composition was conduct-
ed 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 thresh-
olds 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, cm
2
), 
subcutaneous adipose tissue area (SAT, cm
2
) and 
visceral adipose tissue area (VAT, cm
2
). After nor-
malization by patient’s height (m
2
), we used these 
parameters as lumbar skeletal muscle index (SMI, 
cm
2
/m
2
), subcutaneous adipose tissue index (SATI, 
cm
2
/m
2
), and visceral adipose tissue index (VATI, 
cm
2
/m
2
). VSR was calculated by dividing VAT by 
SAT. To assess the muscle density and myosteato-
sis, skeletal muscle radiation attenuation (MRA) 
has also been recorded in HUs. All measurements 
were performed by experienced researcher, ac-
credited for complex image analysis and segmen-
tation techniques. Additionally, we used previous-
ly reported and validated equations to calculate 
appendicular skeletal muscle index (ASMI), lean 
body mass (LBM) and fat mass (FM)
26,29,43,47
:
ASMI (kg/m
2
) = 0.11 x SMI (cm
2
/m
2
) + 1.17
LBM (kg) = 0.030 x Lean Tissue Area (cm
2
) + 6.06
FM (kg) = 0.042 x Total Fat Area (cm
2
) + 11.2
Based on a single abdominal CT image per pa-
tient, 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.
Assessment of myopenia, myopenic 
and visceral obesity, myosteatosis and 
cancer cachexia
Myopenia was defined based on the new recom-
mendations of The European Working Group on 
Sarcopenia in Older People (EWGSOP2), as fol-
lows: SMI < 43 cm
2
/m
2
 for men with BMI < 25, SMI 
< 53 cm
2
/m
2
 for men with BMI ≥ 25, and SMI < 41 
cm
2
/m
2
 for women.
48
Muscle mass in patients with obesity was as-
sessed 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: V AT > 163.8 cm
2
 for men and 
V AT > 80.1 cm
2
 for women.
29,39,47
Preoperative cancer cachexia was defined using 
Fearon et al. criteria.
49
In order to establish optimal cut-off values for 
SMI, V ATI, 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 maxstat package implemented 
in R statistics.
50,51
 This approach is widely used and 
validated in cancer patients.
26,52-55
 The presence of 
myosteatosis was then confirmed based on estab-
lished optimal threshold for MRA: < 35.88 HU in 
patients with a BMI ≥ 25 kg/m
2 
and < 47.41 HU in 
those with a BMI < 25 kg/m
2
.
Age, gender, weight, height 
Referral to Instituteo fO ncologyL jubljana
Patients operated on for retroperitoneal sarcoma 
(September 1999 -J une 2020)
123
Primary localized cases 
89
CT image window
CT scans completed within 
30 days of patients' initial 
visits
Included in the study 
58
Identification of patients with available nutritional 
status data and preoperative CT scans
Significant weight loss
Appetite loss
Weakness
CT/MRI reports
Tumourc haracteristics
Systemic inflammatory markers
Preoperative clinical data
FIGURE 1. Patients’ flow diagram. Out of 123 patients, 58 (47.1%) with primary 
localized retrperitoneal sarcomas (RPS) were included in the study and 65 were 
excluded. 34 (27.6%) were excluded as they presented as primary metastatic 
cases (6), locally recurrent cases (14) or cases with residual disease after 
operation elsewhere (14), and 31 patients (25.2%) were excluded as they had 
CT performed > 30 days from initial assessment or CT image was not technically 
adequate for analysis

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Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 113
Survival and statistical analysis
Final survival follow-up time was set as last fol-
low-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 in-
volving deaths without evidence of disease and 
the occurrence of distant metastases considered 
as competing events. Survival curves were esti-
mated using Kaplan-Meier method. Log-rank test, 
linear regression and Cox proportional hazard 
regression models were used to analyse the rela-
tionship between clinicopathological parameters 
TABLE 1. Clinical characteristics of study population
Clinical characteristic (N = 58) Median (IQR); n (%)
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/m
2
26.0 (24.7 – 29.7)
Nutrition and body composition 
characteristics
Nutritional team support before 
operation
28(48.3%)
Skeletal Muscle Area, cm
2
45.5 (115.9 – 170.1)
Visceral Fat Area, cm
2
104.5 (53.6 – 168.7)
Subcutaneous Adipose Tissue 
Area, cm
2
167.9 (127.9 – 231.6)
Total Fat Area, cm
2
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, cm
2
/m
2
50.2 (44.0 – 55.6)
Appendicular Skeletal Muscle 
Index, cm
2
/m
2
6.70 (6.00 – 7.3)
Myopenia based on estimated 
cut-off value for SMI
a
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%)
Myosteatosis
a
37 (63.7%)
Clinical characteristic (N = 58) Median (IQR); n (%)
Pathologic characteristics and 
postoperative outcome data
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 (8
th
 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; 
a 
cut-off 
values displayed in Table 3

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Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 114
TABLE 2. Comparison of clinical and body composition parameters between myopenic and non-myopenic patients (EGSWOP2 criteria)
Clinicopathological factor Level
a
Myopenic
b
Non Myopenic
b
p
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 vs. 1
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/m
2
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, cm
2
/m
2
 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, cm
2
Median (IQR) 156.4 (103.2−194.4) 185.4 (131.4-254.1) 0.078
Visceral Adipose Tissue Area, cm
2
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, cm
2
/m
2
Median (IQR) 46.8 (30.6−67.2) 64.6(43.9−95.0) 0.048
Visceral Adipose Tissue Index, cm
2
/m
2
Median (IQR) 20.6 (13.2−43.8) 42.3 (24.2−63.6) 0.025
a 
Summary for continuous variables is median (interquartile range) and the statistical test is Kruskal-Wallis/Mann-Whitney; 
b 
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

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 115
and survival. Hosmer-Lemeshow test assessed 
the prediction accuracy (goodness of fit) of regres-
sion models. Hazard ratios (HRs) and 95% confi-
dence intervals (CIs) were obtained.
In addition to body composition parameters, fol-
lowing 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), preopera-
tive radiotherapy, tumour size (cm), and intraoper-
ative blood loss (ml). Results were statistically sig-
nificant if two-sided p value < 0.05 was achieved. 
R statistical software (version 4.2.1, R core Team) 
was used.
A B C D
E
FIGURE 2. Kaplan-Meier curves for OS (A−D) and forest plots of multivariate Cox regression analysis of factors associated with OS (E) and LRFS  
(F). Kaplan-Meier curves for OS according to presence of: (A) myopenia based on EWGSOP2 criteria (red = myopenic, blue = non-myopenic), (B) 
cancer cachexia (red = cachectic, blue = non-cachectic), (C) high SATI (red = SATI above estimated cohort cut-off, blue = SATI below estimated 
cohort cut-off) and (D) high VSR (red = VSR > 0.26, blue = VSR < 0.26); 
EWGSOP2 = The European Working Group on Sarcopenia in Older People revised criteria from 2018; SATI = Subcutaneous Adipose Tissue Index, cm
2
/m
2
; SMI = Skeletal 
Muscle Index; VSR = Visceral-to-subcutaneous adipose tissue area ratio; OS = Overall survival; LRFS = Local recurrence-free survival; HR = Hazard ratio; AIC = Akaike 
Information Criterion
F

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Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 116
Results
Demographic and clinical characteristics
Out of 89 primary localized RPS cases, clinical 
and pathological characteristics and preopera-
tive abdominal CT scans technically adequate for 
analysis were available for 58 patients, represent-
ing the final study cohort (Figure 1). The demo-
graphic 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 pa-
tients 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 vs. 17.5 cm, p = 0.005), SMA (me-
dian 115.8 vs. 149.9 cm
2
, p = 0.019), SMI (median 41 
vs. 53.5 cm
2
/m
2
, p < 0.001), SATI (46.8 vs. 64.6 cm
2
/
m
2
, p = 0.048) and VATI (20.6 vs. 42.3 cm
2
/m
2
, p = 
0.025) (Table 2). There was no significant difference 
in clinical management among myopenic and non-
myopenic group.
Males had significantly higher mean values of 
SMA (163.7 vs. 120 cm
2
, p < 0.001), SMI (52.8 vs. 45.3 
cm
2
/m
2
, p = 0.006), VAT (153.9 vs. 96 cm
2
, p = 0.045) 
and VSR (1.0 vs. 0.5, p = 0.001), while in females 
SAT (227.2 vs. 155.1 cm
2
, p = 0.003) and SATI (85.0 
vs. 49.8 cm
2
/m
2
, p = 0.001) were significantly higher 
(Supplementaly Table 1).
The results of optimal stratification analysis for 
finding cut-off values for SMI, V ATI, SATI, VSR and 
MRA are presented in Table 3 and Supplementaly 
Figures 1−4.
Survival analysis
Overall survival 
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 lev-
els of albumin, CRP, NLR, and AJCC stage were 
associated with OS. Major postoperative morbid-
ity (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 sig-
nificance of myopenia  (myopenic vs. non-myo-
penic: 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).
Local-recurrence free survival
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 vs. high) showed association with LRFS 
(HR 0.94, 95% CI 0.88−1.00, p = 0.052 and HR 8.77, 
95% CI 1.12−68.69, p = 0.039, respectively). Tumour 
size (HR 1.05, 95% CI 1.01−1.09, p = 0.016) and 
AJCC stage (3A−3B vs. 1A−1B, HR 4.46, 95% CI, 
0.95−20.95, p = 0.058) were also associated with 
LRFS. However, SMI and SATI lost statistical sig-
nificance in multivariate model, while tumour size 
and AJCC stage remained significant (Figure 2 F 
and Supplementaly Table 2).
Postoperative outcome and morbidity
We performed univariate and multivariate risk 
factor analysis to evaluate factors associated with 
TABLE 3. Results of optimal stratification analysis for body composition parameters
BMI, kg/m
2
Skeletal
Muscle
Index
a
, cm
2
/m
2
Visceral Adipose 
Tissue Index
b
, cm
2
/m
2
Subcutaneous Adipose 
Tissue Index
b
, cm
2
/m
2
Visceral to 
subcutaneous ratio
c
Muscle Radiation 
Attenuation
d
, HU
Male Female Male Female Male Female Male Female Male Female
< 25 49.21 49.21
61.38 25.55 49.23 86.89 0.26
47.41
≥ 25 49.90 50.64 35.88
BMI = body mass index; HU = Hounsfield Unit; 
a
 adjusted for gender and BMI; 
b
 adjusted for gender only; 
c
 cut-off determined on the level of whole cohort, not stratified 
for BMI nor gender; 
d
 adjusted for BMI only.

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 117
FIGURE 3. Association between overall morbidity following surgery for primary RPS and body composition (A−F) and linear correlation analysis 
between VSR and VATI (G) and VSR and fat mass (H). VSR (F) and intraoperative blood loss (E) independently predicted worse postoperative 
outcome. In multivariate analysis skeletal muscle index (SMA), lean body mass (LBM), subcutaneous adipose tissue area (SAT) and visceral adipose 
tissue area (VAT) were not associated with statistically higher overall postoperative morbidity (A−D). 
VATI = Visceral Adipose Tissue Index; VSR = Visceral-to-subcutaneous adipose tissue area ratio. ȓ
Pearson
 = Pearson Correlation Coefficient; t
Student
 = result of t-test for correlation
A B C
D
E
G H
F

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 118
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 vs. 1, OR 5.56, p = 0.025) and tu-
mour size (OR 1.12, p = 0.007) showed correlation 
with prolonged LOS. Preoperative CRP (OR 1.02, 
p = 0.007), resection status (R1−R2 vs. R0 OR 4.87, 
p = 0.046) and intraoperative blood loss (OR 1.10,  
p = 0.065) were associated with major postoperative 
morbidity (Table 4 and Supplementaly Table 3).
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 signifi-
cantly 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 (pan-
els A–F) summarises our analysis of morbidity fol-
lowing surgery for primary RPS.
Discussion
Our study provided new insight into the associa-
tion between preoperative body composition and 
postoperative and oncologic outcome in primary 
RPS patients. We focused on evaluation of the sig-
TABLE 4. Summary of univariate and multivariate analysis of association between body composition and outcome following surgery for primary RPS
Clinico-pathological 
factor
Length of hospital stay (> 10 days) Clavien-Dindo > IIIa Any complication (overall morbidity)
Uni-variable Multi-variable Uni-variable Multi-variable Uni-variable Multi-variable
OR 
(95% CI)
p
OR  
(95% CI)
p
OR  
(95% CI)
p
OR  
(95% CI)
p
OR  
(95% CI)
p
OR  
(95% CI)
p
Myopenia, 
yes vs. no
a
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 vs. no
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 vs. no
0.01 (0.00-0.001) 0.993 - -
20090605.83 
(0.00-NA)
0.993 - - 279.10 (0.00-NA) 0.993 - -
Myosteatosis,
yes vs. no
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 vs. no
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/m
2
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, 
cm
2
/m
2
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, cm
2
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, cm
2
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 VSR
b
,  
yes vs. no
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, cm
2
/m
2
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, cm
2
/m
2
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 SATI
c
,  
yes vs. no
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 VATI
d
,  
yes vs. no
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; 
a 
assessed by the European Working Group on Sarcopenia in Older People revised criteria from 2018;
b 
defined as VSR > 0.26; 
c 
defined as SATI > 49.23 for males and SATI > 
86.89 for females;
d 
defined as VATI > 61.38 for males and VATI > 25.55 for females
Only significant variables (p < 0.05) were included in multivariate analysis.

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 119
nificance of preoperative nutrition status-related 
syndromes. Furthermore, we examined the predic-
tive 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 as-
sociated 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 inte-
gral component of sarcopenia and also facilitates 
the impairment of muscle function and physi-
cal 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 fit-
ting method analysis for establishing the cut-off 
value for defining low SMI (used for comparative 
and descriptive purposes) resulted in slightly dif-
ferent cut-off values: SMI < 49.21 cm
2
/m
2
 for males 
and females with BMI < 25, and SMI < 49.9 cm
2
/m
2
 
for males with BMI ≥ 25 and SMI < 50.64 cm
2
/m
2
 
for females with BMI ≥ 25. Both EWGSOP2 crite-
ria 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 pre-
dictive value of myosteatosis to sarcopenia or my-
openia for poor survival.
59-61
 Most of this data is 
founded on reports about patients operated on for 
gastrointestinal cancers. In our study cohort my-
osteatosis was also associated with greater over-
all 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 myostea-
tosis and major complication rate and OS in ret-
roperitoneal 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 deter-
mined 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 corre-
sponding height-adjusted indexes VATI and SATI. 
We also considered BMI. Higher value of BMI (≥ 
25) was not associated with oncologic or postoper-
ative outcome. This is in line with number of stud-
ies suggesting that BMI is not reliable prognostic 
parameter for predicting perioperative outcome in 
cancer patients.
63-65
 Stratified for myopenia, com-
parison of the subgroups revealed that body fat and 
VATI were significantly higher in non-myopenic 
patients (median 31.1 vs. 28.1%, p = 0.024 and 42.3 
vs. 20.6 cm
2
/m
2
, p = 0.025, respectively) (Table 2). 
Further on, we used VAT to assess VO applying 
the ESPEN/EASO criteria.
39
 VO predicted poorer 
OS and higher postoperative complication rate. 
VAT alone had no impact on OS or postoperative 
outcome. Recent study on soft tissue sarcoma pa-
tients reported identical findings.
29
 We considered 
VSR into adiposity analysis defining subgroup of 
patients with normal and high VSR (> 0.26) based 
on optimal cut-off analysis. In multivariate analy-
sis VSR was an independent predictor for overall 
complication rate following surgery. High VSR 
group experienced significantly more complica-
tions compared to normal VSR group (33 (89.2%) vs. 
4 (10.8%), p = 0.008). These results are comparable 
with previous reports in which VSR was superior 
to V AT as independent risk factor for death and lo-
cal recurrence. 
34,35,58,66,67
 Linear regression analysis 
showed significant corelation between VSR and 
both VATI and fat mass (Figure 3 – panels G−H 
and Supplementaly Figure 5), confirming the im-
portance of balance between visceral and subcuta-
neous adipose tissue. Recent studies demonstrated 
that predictive values of VSR for cardiovascular 
and metabolic disease incidence is superior to 

Radiol Oncol 2024; 58(1): 110-123.
Ramanovic M et al. / Body composition influence on oncologic and operative outcome in primary RPS 120
VAT.
34,36,37 ,68
 However, to our knowledge, only a few 
studies investigated the impact of VSR and V AT on 
survival and postoperative outcome in patients 
operated on for primary RPS.
29
 Our study under-
lined that high VSR is not only superior to V AT but 
also to BMI in predicting poor oncologic and peri-
operative outcome. These findings suggest that 
VSR better estimates adipose tissue distribution 
and poses an additional difficulty for performing 
the surgery itself. High VSR is strong independ-
ent predictor for overall postoperative morbidity 
(multivariable-adjusted OR 5.05, p = 0.05). On the 
other hand, in the context of survival analysis, the 
multivariate regression model was not able to con-
firm the statistical significance of VSR (p = 0.068). 
This suggests that the impact of VSR on survival of 
RPS patients may be attenuated when considered 
alongside the broader set of predictors. One of the 
reasons may be the fact that, the presence of high 
VSR, as determined by specific gender-independ-
ent cut-off criteria, exhibited a statistically signifi-
cant gender difference, with females having high-
er odds (OR = 4.5, p = 0.027) compared to males. 
Furthermore, we found a statistically significant 
difference in the distribution of SMI, between the 
two groups defined by VSR (high VSR vs. low VSR 
OR = 0.926, p = 0.047). Logistic regression model 
revealed significant association of SMI with a re-
duced odds of the specified outcome within the 
“high VSR” group. Based on our initial hypothesis 
that “high VSR” has a negative impact on surviv-
al, supported by univariate analysis, this implies 
that SMI (approximation of myopenia) may be a 
factor that mitigates the negative impact of “high 
VSR” on patient survival or serves as a positive 
influence, hence confounding the effect of VSR in 
multivariate settings. Further prospective studies 
need to be developed to confirm the importance of 
preoperative VSR for poor postoperative survival. 
In contrast to high VAT, low SATI, independently 
predicted poorer OS (adjusted HR 7.00, p = 0.057). 
Recent study reported similar protective effect of 
higher subcutaneous fat in RPS patients
29
, which 
confirms the known benefits of SATI in processes 
of carcinogenesis and metabolism.
30,69-71
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 indepen-
dently associated with overall survival. This find-
ing underscores the pivotal role of these inflam-
matory biomarkers in clinical practice and man-
agement of surgical oncology patients. Our results 
align with previous findings.
17,18,72-77
 Furthermore, 
our observation suggests that hypoalbuminemia 
identifies a high-risk cohort that may derive great-
er benefits from enhanced nutritional support pre-
operatively. The omission of descriptive statistical 
analysis for serum albumin and NLR, in term of 
patients’ outcome, limits the depth of our data ex-
ploration.
Our study had some limitations. It was a sin-
gle center report including relatively small num-
ber 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 re-
ported the most distinguishable, cohort – specif-
ic, 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 be-
tween preoperative body composition and post-
operative and oncologic outcome in primary RPS 
patients was the main strength of the study.
Conclusions
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 vis-
ceral 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 prog-
nostic factor for postoperative survival. Our find-
ings suggest that clinical nutrition interventions 
towards improving visceral adiposity and myope-
nia may benefit surgical and oncologic outcome in 
primary RPS patients.
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