997

A practical and precise approach to quantification

of body composition in cancer patients using
computed tomography images acquired during
routine care
Marina Mourtzakis, Carla M.M. Prado, Jessica R. Lieffers, Tony Reiman,
Linda J. McCargar, and Vickie E. Baracos

Abstract: Human body composition is important in numerous cancer research domains. Our objective was to evaluate
clinically accessible methods to achieve practical and precise measures of body composition in cancer patients. Dual-
energy X-ray absorptiometry (DXA)-based analysis of fat and fat-free mass was performed in 50 cancer patients and com-
pared with bioelectrical impedance analysis (BIA) and with regional computed tomography (CT) images available in the
patients’ medical records. BIA overestimated or underestimated fat-free mass substantially compared with DXA as the
method of reference (up to 9.3 kg difference). Significant changes in fat-free mass over time detected with DXA in a sub-
set of 21 patients (+2.2 ± 3.2%/100 days, p = 0.003), was beyond the limits of detection of BIA. Regional analysis of fat
and fat-free tissue at the 3rd lumbar vertebra with either DXA or CT strongly predicted whole-body fat and fat-free mass
(r = 0.86–0.94; p < 0.001). CT images provided detail on specific muscles, adipose tissues and organs, not provided by
DXA or BIA. CT presents great practical significance due to the prevalence of these images in patient diagnosis and
follow-up, thus marrying clinical accessibility with high precision to quantify specific tissues and to predict whole-body
composition.
Key words: fat mass, fat-free mass, skeletal muscle, imaging analysis, body mass index, adipose tissue.
Résumé : La composition corporelle est une variable importante dans l’étude de plusieurs cancers. Le but de cette étude
est d’analyser les diverses méthodes d’évaluation de la composition corporelle utilisées en clinique d’oncologie et qui don-
nent de mesures précises. Nous avons comparé les mesures de masse adipeuse et de masse maigre obtenues par absorpsio-
métrie de photons x à deux longueurs d’onde (DXA) auprès de 50 patients atteints d’un cancer à celles obtenues par
l’analyse de l’impédance bioélectrique (BIA) et aux données de tomodensitométrie (CT) disponibles dans le dossier médi-
cal des patients. Comparativement aux valeurs obtenues par DXA, la BIA surestime ou sous-estime de façon importante la
masse maigre ; la différence peut atteindre 9,3 kg. Des variations significatives de la masse maigre observées par DXA
dans le temps chez un sous-échantillon de 21 patients (+2,2 ± 3,2 %/100 jours, p = 0,003), n’ont pu être détectées par
BIA. L’évaluation locale de la masse de tissus adipeux et de la masse de tissus maigres au niveau de la 3e vertèbre lom-
baire par DXA ou par CT est grandement associée à la masse totale de tissus adipeux et de tissus maigres (r = 0,86–0,94;
p < 0,001). Les images fournies par la CT procurent des informations précieuses sur des muscles spécifiques, des tissus
adipeux et des organes, ce que ne peuvent donner la DXA ou la BIA. À cause de la pertinence des images dans un diag-
nostic de cancer et le suivi des patients, la CT constitue un outil important en clinique, car elle procure des résultats quan-
titatifs précis au sujet de certains tissus et de la composition corporelle globale.
Mots-clés : masse adipeuse, masse maigre, muscle squelettique, imagerie, indice de masse corporelle, tissu adipeux.
[Traduit par la Rédaction]

Introduction tients. Increased prevalence or recurrence of breast, prostate,

colorectal, and specific gastro-esophageal cancers is associ-
Body composition, specifically proportions of adipose and ated with obesity (Demark-Wahnefried et al. 2002; Kubo
lean tissue, has many clinical implications in cancer pa- and Corley 2006; Otake et al. 2005; von Hafe et al. 2004).

Received 10 February 2008. Accepted 10 June 2008. Published on the NRC Research Press Web site at apnm.nrc.ca on 25 September
2008.
M. Mourtzakis,1 T. Reiman, and V.E. Baracos.2 Department of Oncology, University of Alberta, 11560 University Avenue, Cross
Cancer Institute, Edmonton, AB T6G 1Z2, Canada.
C.M.M. Prado, J.R. Lieffers, and L.J. McCargar. Department of Agricultural, Food and Nutritional Science, University of Alberta,
11560 University Avenue, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada.
1
Present address: Department of Kinesiology, University of Waterloo, 200 University Avenue W., Waterloo, ON N2L 3G1, Canada.
2
Corresponding author (e-mail: vickieb@cancerboard.ab.ca).

Appl. Physiol. Nutr. Metab. 33: 997–1006 (2008) doi:10.1139/H08-075 # 2008 NRC Canada
998
Involuntary weight loss, involving muscle and fat loss, fre-
quently accompanies advanced disease and is associated
with poor response to treatment and shortened survival
(Dewys et al. 1980; Vigano et al. 2000). Also, fat and lean
tissue compartments represent sites for distribution of lipid-
and water-soluble drugs, respectively, and are likely deter-
minants of chemotherapy efficacy and toxicity (Aslani et al.
2000; Prado et al. 2007).
Methods for evaluating human body composition have
been developed and validated for research focused on aging
and chronic diseases (e.g., obesity, chronic obstructive pul-
monary disease) (Baumgartner et al. 1998; Cosqueric et al.
2006; Ross et al. 2000; Steiner et al. 2002; Kyle et al.
2004a, 2004b). Through this research, distinct tissues have
been associated with specific health outcomes. For example,
insulin resistance is associated with visceral adipose tissue
accumulation (Otake et al. 2005; Ross et al. 2000) and loss
of skeletal muscle is associated with physical disability
(Baumgartner et al. 1998) and disease outcomes such as no-
socomial infections (Cosqueric et al. 2006).
Dual energy X-ray absorptiometry (DXA), magnetic reso-
nance imaging (MRI), and computed tomography (CT) are
generally regarded as gold standard methods in the evalua-
tion of human body composition. Bioelectrical impedance
analysis (BIA) is an inexpensive, expedient, and accessible
method that has been commonly used to measure body com-
position in clinical populations (Kyle et al. 2004a, 2004b).
Although BIA is safe and inexpensive and does not expose
patients to radiation, it may not have the specificity and pre-
cision of DXA, MRI, and CT. DXA is not usually available
in cancer settings; however, CT imaging is a clinically ac-
cessible alternative. Here, we evaluated regional CT images
acquired during routine patient care, as a potential resource
to discriminate and to quantify important and distinct fea-
tures of the body composition of patients with advanced
cancer. CT image analysis at defined skeletal landmarks has
already been established as a precise means of following
gain or loss of tissue over time (Ross et al. 2000). Single
images at key lumbar vertebral landmarks are known to be
good correlates of whole-body fat and lean tissue mass in
healthy populations (Shen et al. 2004a, 2004b). A secondary
aim of this study was to compare estimates of whole-body
composition obtained by BIA and CT, with those obtained
by DXA.
Materials and methods
Subjects and study design
Fifty-one patients (n = 51) with locally advanced or meta-
static non-small cell lung or colorectal cancer provided writ-
ten consent to participate; *96% of these patients were
Caucasian. Demographic features of the sample were com-
pared with those of a population cohort of patients present-
ing with the same diseases (n = 1806) at our regional cancer
centre. The study was approved by the Research Ethics
Board of the Alberta Cancer Board.
One patient exceeded the weight limit of the DXA scan-
ner and 3 patients were excluded from BIA analysis owing
to calused feet, which impeded proper conductivity.
Twenty-one participants returned for a second DXA and
BIA evaluation after *8 weeks. Initial DXA and BIA meas-
Appl. Physiol. Nutr. Metab. Vol. 33, 2008
urements were scheduled to coincide with CT imaging for
disease diagnosis or treatment follow-up. Patients were not
requested to have a CT scan solely for body composition
analysis; rather, CT images were acquired for the purposes
of routine medical care. It should be noted that CT imaging
in clinical oncology is used to detect tumors in specific ana-
tomical sites mostly in the abdomen or thorax, and whole-
body imaging is not done. Thirty-one patients (11 with non-
small cell lung cancer; 20 with colorectal cancer) had
concurrent CT images including the lumbar area.
Body composition methodology
DXA precisely depicts whole-body fat mass (FM) and fat-
free mass (FFM), has the capacity for regional analysis, and
is widely used to assess skeletal muscle based on analysis of
the limbs (Baumgartner et al. 1998; Heymsfield et al. 1990).
MRI and CT allow the precise segregation of individual tis-
sues (Fig. 1). Tissue areas in single MRI/CT images at spe-
cific lumbar landmarks relate significantly to whole-body
muscle in healthy adults and these relationships are linear
over a very wide range (Shen et al. 2004a, 2004b); for this
reason scans including the lumbar region were considered.
BIA is a convenient and cost-effective, but indirect, measure
that is based on disparate electrical conductivity of fat and
lean tissue. We also used a common anthropometric descrip-
tor: body mass index (BMI (kg/m2) = body mass/height2).
Patients were instructed to refrain from consuming alco-
hol for 24 h, food for 8–12 h, and fluids for 2 h prior to
DXA and BIA. Height and mass were measured with sub-
jects barefoot and in a hospital gown, followed immediately
by BIA and DXA assessments. Principles and methods of
DXA analysis can be found elsewhere (Heymsfield et al.
1997). We used a General Electric Lunar Prodigy High
Speed Digital Fan Beam X-Ray-Based Densitometer and en-
CORE 9.20 software for analysis. Our coefficient of varia-
tion was 2.0% for fat mass and 0.8% for lean mass using
this instrument. DXA scans were partitioned at the acromio-
humeral and pelvic-femoral joints (Fig. 1) where tissues
located distally from these partitions were characterized as
appendicular tissues and the medial tissues were character-
ized as trunk (Fig. 1). Appendicular FFM represents skeletal
muscle in DXA analysis (Baumgartner et al. 1998;
Heymsfield et al. 1990). Regional analysis at the 3rd lum-
bar vertebra (L3) was conducted (Fig. 1), and the identical
field of view was used for the CT image analysis. Since
the height of L3 varied among patients (3.79 ± 0.41 cm),
tissue mass from DXA regional analysis was standardized
to a 1-cm-thick slice equivalent; CT images were analyzed
as cross-sectional areas and thus the height of L3 was irrel-
evant.
Details of the use of CT image analysis to determine body
composition can be found elsewhere (Heymsfield et al.
1997). Images were analyzed for tissue cross-sectional area
(cm2) using Slice-O-Matic software V4.3 (Tomovision,
Montreal, Quebec, Canada). CT Hounsfield unit thresholds
were –29 to 150 for skeletal muscle (Heymsfield et al.
1990), –190 to –30 for subcutaneous and intra-muscular adi-
pose tissue (Heymsfield et al. 1990), and –50 to –150 for
visceral adipose tissue (Miller et al. 1998). Tissue bounda-
ries were manually corrected as necessary. Two consecutive
images extending from the 3rd lumbar vertebrae in the infe-
# 2008 NRC Canada
Mourtzakis et al.
Fig. 1. DXA whole-body and CT regional image analysis at 3rd
lumbar vertebra (L3).
rior direction were assessed for adipose tissue (visceral, sub-
cutaneous, and intramuscular), total lean tissue, and total
muscle (psoas, erector spinae, quadratus lumborum, trans-
versus abdominus, external and internal obliques, and rectus
abdominus). Total fat-free tissue analysis at L3 comprised
bone and soft tissues excluding intestinal contents. The coef-
ficient of variability for the skeletal muscle measurements
was 1.6% and for adipose tissue measurements it was 2.3%.
Spleen and liver volumes were computed by multiplying the
cross-sectional area of each consecutive image by the dis-
tance between each image (5 mm). The coefficient of varia-
bility for spleen volume was 2.8% and for liver volume it
was 2.6%.
A single frequency electrical signal (50 kHz, 500 mA) was
used for foot-to-foot BIA analysis (Tanita Body Composi-
tion Analyzer TBF-300A). Foot-to-foot analysis has been
previously shown to generate similar resistance measures at
50 kHz to hand-to-foot BIA (Cox-Reijven et al. 2002;
Ritchie et al. 2005). Our BIA instrument generated resist-
ance values that were used along with patient height, age,
and sex to calculate FFM from predictive equations in the
literature. We included 2 formulas from the European Soci-
ety of Clinical Nutrition and Metabolism guidelines (Kyle et
al. 2004a, 2004b) that were derived from large populations:
one from Deurenberg et al. (1990) for the elderly and one
999
from Steiner et al. (2002) for chronic obstructive pulmonary
disease. FFM estimates also included those derived in cancer
patients (Simons et al. 1995; Isenring et al. 2004), normal-
weight adults (Segal et al. 1988), pulmonary disease (Kyle
et al. 1998), and obesity (Gray et al. 1989) as our study pa-
tients generally presented one or more of these features.
FFM derived from each of these equations was compared to
DXA. Isenring et al. (2004) performed foot-to-foot BIA
analysis with these equations.
Units of measurement and expression
Fat and fat-free tissues, evaluated with DXA, are ex-
pressed conventionally in kilograms. CT data are presented
in the units of the primary measure, cross-sectional areas
(cm2). When specific fat-free tissues (i.e., skeletal muscle)
measured with CT were compared with FFM measured with
DXA, bone mineral content was excluded (i.e., Figs. 5 and
6); for all other fat-free tissue comparisons, bone mineral
content was included (i.e., Figs. 2, 3B, 4B, 4D; Tables 2, 3).
For the purpose of comparing to literature values
(Baumgartner et al. 1998), measurements for appendicular
skeletal muscle using DXA and muscle measured by CT
(Fig. 6) were normalized to each patient’s height2. Since the
timing of CT scans was dictated by clinical factors and was
different for each patient, loss or gain of tissue over time
was expressed as a percentage and was divided by the
number of days between scans. This value was then
multiplied by 100 days to provide a standardized unit,
% change/100 days, for more accurate comparisons be-
tween patients. The same approach was used for calculat-
ing changes in tissue measured by DXA and BIA
(Table 2).
Statistics
Data are presented as means ± SD. Statistical significance
was accepted at p < 0.05. Student’s t test and the 2 test
were used as indicated in the results section. Pearson corre-
lations were used to compare body compositions determined
by DXA, CT, and BIA, and included both sexes because age
and sex do not impact these relationships (Shen et al.
2004b). For the relationships that would be used for extrap-
olating regional tissue to corresponding whole-body mass,
we have included the standard error of estimate (SEE) to
provide the accuracy of the regression model relative to the
population studied. The mean absolute residual error (MRE)
is also presented to indicate the error associated with indi-
vidual data relative to the predictive equation. A Bland and
Altman plot (Bland and Altman 1986) was used to evaluate
the sensitivity of the equation for predicting FFM using BIA
relative to DXA-based measurements.
Results
Characteristics of the study participants were highly com-
parable with those of the overall population cohort present-
ing with similar diseases and stages (Table 1). Over 50% of
both populations were overweight or obese and a small pro-
portion (4%–6%) were underweight. The patients BMI
ranged from 17.7 to 35.9 kg/m2. These patients were within
the range considered acceptable for BIA analysis (Kyle et al.
2004a, 2004b) as well as DXA.
# 2008 NRC Canada
1000 Appl. Physiol. Nutr. Metab. Vol. 33, 2008

Fig. 2. An assessment of agreement between fat-free mass (FFM)

as calculated by Kyle et al. (1998) for BIA and FFM measured with

P value (sex)
DXA are demonstrated with Bland and Altman plot (n = 48).

P value
0.033
n.s.

n.s.

n.s.
patients (n = 21)a

From Health Canada 2003. Canadian guidelines for body weight classification in adults. Available from http://www.healthcanada.ca/nutrition [accessed 12 December 2006].
Female study

% Patients
72.2±22.6

Note: Student’s t test was used for age, weight, and BMI comparisons. 2 test was used for comparing BMI classifications. BMI, body mass index; n.s., not significant.
26.9±8.2
61±11

10
38
33
19
Male study patients

% Patients
84.1±16.1
(n = 30)a

26.9±4.5
65±10

BIA
40
23
37
0

Compared with other prediction equations tested, that of

Kyle et al. (1998) gave the best estimate of FFM compared
P value (population

with the reference method, DXA. The deviation between es-

vs. study patients)

timated FFM from BIA using the predictive equation of

Kyle et al. (1998) is depicted in a Bland and Altman (1986)
plot (Fig. 2), demonstrating that BIA estimates of FFM were
P value

often substantially discrepant from DXA determinations,

n.s.
n.s.
n.s.
n.s.

which range from –9.3 to +7.3 kg. This discrepancy was

not systematic: BIA largely underestimated FFM in patients
with higher FFM and overestimated in patients with lower
FFM. Since BIA generated poor FFM estimates, which
were required for estimating fat mass or appendicular
Study patients

muscle mass, these were not computed. BIA also lacked the
% Patients
79.2±19.7
(n = 51)a

26.9±6.2

capacity to detect overall changes in FFM compared with

63±10

DXA. For the patients in Table 2, a mean gain of FFM of

2.2 ± 3.2%/100 days (p < 0.05) was detected by DXA. How-
27
39

29
4

ever, a parallel analysis of the same patients by BIA ren-

dered a mean rate of change of –1.0 ± 6.8%/100 days
which compared poorly to DXA and had a large standard
Population cohort

deviation.
(n = 1806)a

% Patients
73.9±17.1

Regional and whole-body composition: DXA vs. CT

25.7±5.2

analysis
65±12

On a whole-body basis, study patients were on average

34
42

18
Table 1. Physical characteristics of patients.

34.0% ± 9.4% (9.9 ± 3.8 kg/m2) fat and 63.2% ± 8.9%

(16.5 ± 2.6 kg/m2) fat-free tissue (excluding bone mineral
content) by DXA analysis. Fat and muscle tissue measure-
ments using CT analysis at L3 are shown in Table 3. The
range of lumbar total muscle cross-sectional areas are com-
BMI classifications (kg/m2)b

parable to those we recently observed in a cohort of 250

Normal weight (18.5–24.9)

cancer patients (155.1 ± 38.6 cm2; range 79.2–271.5 cm2,

Overweight (25.0–29.9)

Data are means ± SD.

Prado et al. 2008). To determine whether L3 was representa-

Underweight (<18.5)

tive of the whole body, a series of comparisons were con-

ducted (Figs. 3–5). The L3 FM and FFM to whole-body
Obese (>30.0)
BMI (kg/m2)

relationships were evaluated with DXA (Figs. 3A and 3B,

Weight (kg)

respectively):
Age (y)

 whole-body FM (kg) = 34.61  [FM at L3 (kg/1 cm

a

slice)] – 2.17; r = 0.82; p < 0.001

# 2008 NRC Canada
Mourtzakis et al. 1001

Table 2. Rate of change (% change/100 days) in fat-free mass (FFM) measured with DXA and BIA
(n = 21).

BIA analysis DXA analysis

Appendicular
Whole body Whole body skeletal muscle Trunk
Mean rate of changea –1.0±6.8 2.2±3.2 1.0±4.1 3.5±5.8
P value (mean rate vs. zero change)b 0.51 0.003 0.26 0.008
Pearson’s correlation coefficient to — — 0.49 0.88
whole-body FFM
a
Data are means ± SD.
b
Paired t test was used to identify statistical difference in whole-body FFM between DXA and BIA
measurements (p < 0.05).

Table 3. Cross-sectional area of total and specific adipose and fat-free tissue depots measured with CT (cm2) in the L3 region.

% Difference,
All patients (n = 31) Males (n = 19) Females (n = 12) females vs. malesa P valueb (sex)
Adipose tissue
Total adipose tissue 350.3±195.7 417.6±174.1 243.7±186.0 –41.6 0.01
Subcutaneous 173.4±87.1 173.2±50.7 173.7±128.3 0.30 0.99
Visceral 161.4±139.3 225.8±138.4 59.5±55.4 –73.6 <0.001
Intramuscular 15.2±10.0 18.2±11.0 10.5±5.9 –42.3 0.03
Fat-freec and individual muscle tissues
Total fat-free tissue 349.6±68.8 384.7±49.9 294.0±57.9 –23.5 <0.001
Total muscle tissue 145.2±36.4 168.4±24.5 108.1±14.3 –35.8 <0.001
Psoas 20.7±5.6 23.6±5.0 16.0±2.1 –32.2 <0.001
Paraspinal muscles 58.3±12.5 65.9±9.4 46.4±5.0 –29.6 <0.001
Rectus abdominus 12.1±4.9 14.6±4.4 8.0±2.2 –45.2 <0.001
Oblique and transversus 53.9±16.8 64.1±12.0 37.7±8.0 –41.2 <0.001
abdominus
Note: Data are means ± SD.
a
Percent calculations resulting in a negative number indicate that females have a lower proportion of a given tissue than males (i.e., fat-free mass) and a
positive number suggests that females have a greater proportion of a particular tissue than males (i.e., fat mass).
b
Student’s t test was used for statistical test.
c
Note that fat-free mass measurements include bone mineral content.

 whole-body FFM (kg) = 101.9  [FFM at L3 (kg/1 cm
slice)] + 9.023; r = 0.89; p < 0.001
The relationships between DXA and CT-based measure-
ments were also resolved for fat and fat-free tissue. CT and
DXA were directly compared at L3 (Figs. 4A and 4B, re-
spectively):
 FM at L3 using DXA (kg/1 cm slice) = 0.001  [fat tis-
sue at L3 using CT (cm2)] + 0.30; r = 0.97; p < 0.001
 FFM at L3 using DXA (kg/1 cm slice) = 0.001  [fat-
free tissue at L3 using CT (cm2)] + 0.034; r = 0.84; p <
0.001
CT at L3 was subsequently compared with corresponding
whole-body DXA measures of FM and FFM (Figs. 4C and
4D, respectively):
 whole-body FM (kg) = 0.042  [fat tissue at L3 using
CT (cm2)] + 11.2; r = 0.88; p < 0.001; SEE = 0.80 kg;
MRE = 3.49 ± 2.31 kg
 whole-body FFM (kg) = 0.14  [fat-free tissue at L3
using CT (cm2)] + 0.72; r = 0.83; p < 0.001; SEE =
1.2 kg; MRE = 5.23 ± 3.54 kg
The regressions presented here ranged from r = 0.83 to
0.97 for FM and FFM and were highly comparable to corre-
lations of single-image to whole-body fat (r = 0.842–0.963)
and muscle (r = 0.712–0.924) previously demonstrated using
MRI in a healthy population (Shen et al. 2004a).
Skeletal muscle
CT analysis of skeletal muscle at L3 strongly related to
whole-body FFM and to appendicular skeletal muscle mass
as measured by DXA, respectively:
 whole-body FFM (kg) = 0.30  [skeletal muscle at L3
using CT (cm2)] + 6.06; r = 0.94; p < 0.001; SEE =
0.72 kg; MRE = 2.94 ± 2.46 kg (Fig. 5)
 Appendicular skeletal muscle / height2 (kg/m2) = 0.11 
[skeletal muscle at L3 using CT / height2 (cm2/m2)] +
1.17; r = 0.89; p < 0.001; SEE = 0.10 kg/m2; MRE =
0.45 ± 0.33 kg/m2 (Fig. 6)
The latter two relationships are potentially useful for re-
lating CT-based measures with those made with other meth-
ods. For example, sex-specific cutoffs for low appendicular
muscle mass have been defined using DXA analysis
(males, <7.26 kg/m2; females, <5.45 kg/m2). These cutoffs
for low muscle mass associate with physical disability, falls,
and mortality in elderly adults. The equation derived from
# 2008 NRC Canada
1002
Fig. 3. Regional DXA analysis of (A) fat mass (FM) and (B) fat-
free mass (FFM) at the L3 region correlates with DXA analysis of
whole-body FM and FFM (n = 50).
the analysis in Fig. 6 suggests that corresponding cutoffs for
lumbar skeletal muscle index are *<55.4 cm2/m2 for males
and <38.9 cm2/m2 in females. The incidence of low muscle
mass was considerable; 28 of 50 patients showed this fea-
ture.
Specific tissue analysis: DXA and CT
Whereas FFM in limbs is skeletal muscle, FFM in the
trunk is a composite of muscle, liver, spleen, tumor, and
other organs (Heymsfield and McManus 1985). Trunk FFM
represented 58.1% ± 3.7% of whole-body FFM. The liver
volume, which in some patients included hepatic meta-
stases, was 1.7 ± 0.5 L (range 0.7–3.0 L). Spleen volume
ranged 5-fold (from 110 to 680 mL). Because the trunk
represented a large fraction of whole-body FFM, change in
whole-body FFM was related to changes in trunk FFM (r =
0.88, p < 0.05, Table 2). In contrast appendicular skeletal
muscle mass related less well with the rate of change in
whole-body FFM (r = 0.49, p < 0.05, Table 2).
Specific tissue analysis: abdominal region
The power of CT imaging to discriminate specific tissue
changes (skeletal muscle, liver, spleen, total adipose tissue)
is illustrated in a series of CT images in a colorectal cancer
patient (Table 4). A progressive loss of *7.0 kg of adipose
tissue was evident following an earlier period of fat gain of
*1.7 kg. Loss of skeletal muscle of *3.0 kg occurred dur-
Appl. Physiol. Nutr. Metab. Vol. 33, 2008
ing the final 5 months of life while simultaneous late-stage
hepatomegaly and extensive hepatic metastases were evident
(*+2.4 L in the final 70 days of life). This concurrent loss
of muscle and gain in liver mass clearly indicates that im-
portant tissue-specific changes could occur that would not
be detected by either DXA or BIA.
Discussion
CT imaging as a method of choice for clinical measure of
body composition in oncology patients
We propose that CT image analysis is a clinically practi-
cal and precise method of evaluating the unique features of
body composition in patients with cancer. The potential ap-
plicability of this approach is very broad, since imaging is a
key basis of diagnosis and follow-up. More than 90% of
patients with advanced cancers at our centre have CT im-
ages that could be evaluated in the manner described here.
CT/MRI and DXA stand as ‘‘gold standards’’ in human
body composition analysis, however, CT/MRI images have
greater availability in cancer centres compared with DXA.
CT images encompassing selected regions of the body are
frequently taken as part of standard care and could be inter-
preted to provide information on body composition without
incremental cost or radiation exposure. CT and MRI are the
only modalities that can be used to precisely quantify spe-
cific fat depots, muscles and organs. These attributes of CT
imaging analysis place this tool in the forefront as a princi-
pal instrument for clinical measures and research.
Predictive value of regional analysis for whole-body
composition
Tissue areas in single MRI/CT images at lumbar land-
marks relate significantly to whole-body muscle (r2 =
0.855) and fat (r2 = 0.927) in healthy adults and these rela-
tionships are linear over a very wide range of total fat mass
(10–60 kg) and muscle mass (10–60 kg) (Shen et al. 2004a).
Our work provides evidence that the linearity of relation-
ships between L3 and whole-body fat and fat-free compart-
ments are maintained in cancer patients. These relationships
are potentially useful for relating CT-based assessments with
measures made with other methods. For example, the rela-
tionship illustrated in Figs. 5 and 6 allows CT-based evalua-
tions to be related to measures of whole-body fat-free mass
and appendicular skeletal muscle that are often found in the
literature. Finally, within the limits of its error terms, re-
gional CT imaging is a practical surrogate for whole-body
imaging. CT can be used with reasonable precision to pre-
dict whole-body measures for individual patients, these rela-
tionships provide a highly precise method (with standard
error of our regression models of less than 1.2 kg) for pre-
dicting corresponding whole-body measures in groups of pa-
tients.
A need to discriminate behaviour of distinct elements of
the lean body mass
Whole-body lean mass cannot be interpreted as a single
entity. The trunk and appendices clearly show disparate be-
haviours. Although FFM in the limbs (skeletal muscle) did
not change over time, trunk FFM increased progressively
and had a strong influence on whole-body FFM. This dispa-
# 2008 NRC Canada
Mourtzakis et al.
Fig. 4. Fat and fat-free tissue measured with CT at L3 were related to (A) fat mass (FM) and (B) fat-free mass (FFM) measured with DXA,
and (C) whole-body FM and (D) whole-body FFM measured with DXA (n = 31).
Fig. 5. Muscle analysis using CT images at the L3 region was cor-
related with DXA measurements of whole-body fat-free mass
(FFM) (n = 31).
rate behaviour between the trunk and limbs of cancer pa-
tients was also reported by Fouladiun et al. (2005), who
showed that advanced cancer patients lost appendicular skel-
etal muscle mass while gaining FFM in the trunk. The trunk
is a heterogeneous composite of lean tissues including skel-
etal muscle, liver, spleen, tumor, as well as intestines and
their contents, and each tissue may exhibit distinct changes
1003
during disease progression (Fouladiun et al. 2005;
Heymsfield and McManus 1985).
A gain or loss of whole-body FFM is often used as a clin-
ical outcome in evaluating anorexia–cachexia therapy based
on the assumption that a gain in FFM is beneficial (i.e.,
composed of functional skeletal muscle). Here we demon-
strated that a gain in FFM may actually indicate disease pro-
gression (e.g., the 2.4 L increase in metastatic disease in the
liver of the example patient). A tissue-specific approach to
following lean tissue changes would thus seem highly rele-
vant.
The presence of ascites and alterations in hydration status,
two factors that are frequently present in advanced cancer
patients are already known to confound the results of BIA
analysis (Kyle et al. 2004b; Sarhill et al. 2000). Further-
more, BIA identifies whole-body FFM as a single entity,
and makes no account of the proportions of different lean
tissues. We showed that the strongest correlations for BIA
estimates of FFM were generated by the equation of Kyle
et al. (1998), which were substantially discrepant with DXA
by up to *9 kg. However, it is important to consider that
the regression from Kyle et al. (1998) was derived using a
DXA Hologic scanner as opposed to the Lunar Prodigy
scanner that was used in the present study. As discussed in
Genton et al. (2006), the difference in equipment may con-
tribute, in part, to the discrepancy between BIA and DXA
FFM values. However, equation from Kyle et al. (1998)
showed the best correlation between BIA and DXA, and
# 2008 NRC Canada
1004 Appl. Physiol. Nutr. Metab. Vol. 33, 2008

Fig. 6. CT-based muscle analysis at L3 was strongly related to appendicular skeletal muscle mass measured with DXA (n = 31). DXA-
based low muscle levels [males <7.26 kg/m2; females <5.45 kg/m2 (10)] generated corresponding CT values [males <55.4 cm2/m2 and
females <38.9 cm2/m2].

Table 4. Progressive tissue changes during the last year of life in a female patient who died at the age of 62 years
of metastatic colorectal cancer.

Estimated tissue sizea

No. of days between CT Total appendicular skeletal Total body adipose
image and date of death muscle mass (kg) tissue (kg) Liver (L) Spleen (L)
264 13.8 14.2 1.7 0.12
163 13.8 (0) 15.9 (+1.7) 1.6 (–0.1) 0.11 (–0.01)
70 13.6 (–0.2) 9.8 (–6.1) 1.9 (+0.3) 0.15 (+0.04)
9 10.8 (–2.8) 9.0 (–0.8) 4.0 (+2.1) 0.19 (+0.04)
Note: Values in parentheses indicate change since previous scan.
a
Appendicular skeletal muscle and total body adipose tissue were estimated from tissue cross sectional area at L3, using the
regression equations in Figs. 5 and 3C, respectively. Liver and spleen volumes were calculated using Sliceomatic software as
described under Materials and methods.

these inconsistencies between DXA and BIA are in accord-
ance with data from Simons et al. (1995). BIA has been an
outcome measure in randomized clinical trials of anorexia–
cachexia therapy (Shang et al. 2006); however, we have
shown that BIA also lacks precision in detecting changes in
FFM over time. Sample-size calculations based on the stand-
ard deviations in our data suggest that detecting a 5%
change in FFM would require almost 4 times more patients
if using BIA rather than DXA.
Specific methods for applications in clinical oncology
Regional CT images are ubiquitously available for cancer
patients as they are normally performed for staging as well
as assessing treatment success or disease progression.
Whole-body CT scans are rarely taken. The field is limited
to the expected sites or tumor in a specific anatomical re-
gion of the body (e.g., abdominal region which usually in-
cludes the most inferior thoracic vertebrae (T10–T12) and
the superior lumbar vertebrae (L1–L4)). These fields nor-
mally encompass organs such as liver and spleen, for which
volumes can be determined. Usual diagnostic scans do not
encompass the entire volume of any specific muscle groups
or adipose tissues, so the available information on these is
limited to cross-sectional areas. Measurements of tissue
areas are exceedingly precise for looking at longitudinal
change within an individual and very powerful for detecting
the rate of loss or gain. Additionally, cross-sectionals area
can be extrapolated to whole-body measures.
Body composition of cancer patients may be followed for
different purposes. For example, prevalence of colorectal
cancer may be specifically associated with increased visceral
adipose tissue (Otake et al. 2005). CT/MRI image analysis is
the only approach that permits the explicit evaluation of vis-
ceral adipose tissue; DXA cannot discriminate visceral adi-
pose tissue. BIA is not only incapable of discriminating
between different depots of adipose tissue, but total fat
mass is calculated as body weight minus estimated fat-free
mass, which in turn showed important discrepancy with
DXA. Body composition change during involuntary weight
loss is complex and involves concurrent changes in many
tissues, all of which can be followed with high precision us-
ing CT/MRI analysis. DXA is also useful in this application,
provided the limbs (representing muscle) and trunk are con-
sidered separately. The disparate proportions and behaviour
of the different tissues within the trunk compartment can
only be appreciated with CT/MRI.
# 2008 NRC Canada
Mourtzakis et al.
In clinical pharmacology, proportions of fat and lean tis-
sue in the body may represent sites for the distribution of
lipid- and water-soluble drugs, respectively. Whole-body
DXA is appropriate for this determination; however, the re-
gressions presented here can be used to extrapolate single-
slice values from CT analysis to corresponding whole-body
values. In related work (Prado et al. 2007, 2008), we used
these relationships to predict whole-body FFM of colorectal
cancer patients, specifically the relationship between muscle
area at L3 with whole-body FFM (Fig. 5; r = 0.94). We
were then able to estimate the variation in 5-fluorouracil
doses per unit of FFM between patients and to relate this
variation to 5-fluorouracil toxicity. Finally, where there
might be interest in the hepatic mass in relation to the me-
tabolism of drugs, analysis of in CT/MRI images provides a
precise means of quantifying liver volume.
Body composition features of patients with advanced
cancer
Our study participants were representative of a larger pop-
ulation of patients seen at our centre. Study participants had
a wide range of BMIs, with an average of 34% body fat,
which is consistent with the definition of obesity
(Baumgartner 2000). More than 50% of our patients were
below the cutoffs for sarcopenia (low skeletal muscle mass)
described by Baumgartner et al. (1998). The concurrent
presence of obesity and low muscle mass represent a popu-
lation profile tending toward a body phenotype referred to as
sarcopenic obesity. Sarcopenic obesity is associated with in-
creased health risks compared with patients who are either
obese or sarcopenic (Baumgartner 2000; Demark-
Wahnefried et al. 2002). These risks include longer hospital
stays, increased infectious and non-infectious complications,
and increased mortality in hospital (Cosqueric et al. 2006;
Bochicchio et al. 2006). Sarcopenic obesity is associated
with poor functional status and mortality in cancer patients
(Prado et al. 2008).
Conclusion
CT imaging, with its excellent resolution of adipose tissue
and skeletal muscles, provides a capacity to test the implica-
tions of these distinct attributes in cancer patients. Regional
analysis of fat and lean tissue are highly correlated to corre-
sponding whole-body compartments and can provide precise
quantification of specific adipose tissues, skeletal muscles,
and organs. While DXA also provides high precision, it is
not readily available in cancer centres. In contrast, BIA is
clinically available, but provides highly discrepant results
when compared with gold standard methodologies.
Acknowledgements
This study received financial support from the Canadian
Institute of Health Research and the Alberta Cancer Board.
M. Mourtzakis was supported by a Translational Research
Training in Cancer fellowship from the Canadian Institute
of Health Research. We would like to thank Lisa Martin,
Vishesh Kumar, Abigail Tonkin, Dana Wilkinson, Michelle
Houle, and Stefanie Alloway for their assistance in conduct-
ing this study.
1005
References
Aslani, A., Smith, R.C., Allen, B.J., Pavlakis, N., and Levi, J.A.
2000. The predictive value of body protein for chemotherapy-
induced toxicity. Cancer, 88: 796–803. doi:10.1002/(SICI)1097-
0142(20000215)88:4<796::AID-CNCR10>3.0.CO;2-P. PMID:
10679649.
Baumgartner, R.N. 2000. Body composition in healthy aging. Ann.
N. Y. Acad. Sci. 904: 437–448. PMID:10865787.
Baumgartner, R.N., Koehler, K.M., Gallagher, D., Romero, L.,
Heymsfield, S.B., Ross, R., et al. 1998. Epidemiology of sarco-
penia among the elderly in New Mexico. Am. J. Epidemiol.
147: 755–763. PMID:9554417.
Bland, J.M., and Altman, D.G. 1986. Statistical methods for asses-
sing agreement between two methods of clinical assessment.
Lancet, 1: 307–310. PMID:2868172.
Bochicchio, G.V., Joshi, M., Bochicchio, K., Nehman, S., Tracy,
J.K., and Scalea, T.M. 2006. Impact of obesity in the critically ill
trauma patient: a prospective study. J. Am. Coll. Surg. 203: 533–
538. doi:10.1016/j.jamcollsurg.2006.07.001. PMID:17000398.
Cosqueric, G., Sebag, A., Ducolombier, C., Thomas, C., Piette, F.,
and Weill-Engerer, S. 2006. Sarcopenia is predictive of nosoco-
mial infection in care of the elderly. Br. J. Nutr. 96: 895–901.
doi:10.1017/BJN20061943. PMID:17092379.
Cox-Reijven, P.L.M., Van Kreel, B., and Soeters, P.B. 2002. Bio-
electrical impedance spectroscopy: alternatives for the conven-
tional hand-to-foot measurements. Clin. Nutr. 21: 127–133.
doi:10.1054/clnu.2001.0521. PMID:12056784.
Demark-Wahnefried, W., Kenyon, A.J., Eberle, P., Skye, A., and
Kraus, W.E. 2002. Preventing sarcopenic obesity among breast
cancer patients who receive adjuvant chemotherapy: results of a
feasibility study. Clin. Exerc. Physiol. 4: 44–49. PMID:
16946801.
Deurenberg, P., van der Kooij, K., Evers, P., and Hulshof, T. 1990.
Assessment of body composition by bioelectrical impedance in a
population aged greater than 60 y. Am. J. Clin. Nutr. 51: 3–6.
PMID:2296928.
Dewys, W.D., Begg, C., Lavin, P.T., Band, P.R., Bennett, J.M.,
Bertino, J.R., et al. 1980. Prognostic effect of weight loss prior
to chemotherapy in cancer patients. Eastern Cooperative Oncol-
ogy Group. Am. J. Med. 69: 491–497. doi:10.1016/S0149-
2918(05)80001-3. PMID:7424938.
Fouladiun, M., Körner, U., Bosaeus, I., Daneryd, P., Hyltander, A.,
and Lundholm, K. 2005. Body composition and time course of
changes in regional distribution of fat and lean tissue in unse-
lected cancer patients on palliative care—correlations with food
intake, metabolism, exercise capacity, and hormones. Cancer,
103: 2189–2198. doi:10.1002/cncr.21013. PMID:15822132.
Genton, L., Karsegard, V.L., Zawadynski, S., Kyle, U.G., Pichard,
C., Golay, A., and Hans, D.B. 2006. Comparison of body weight
and composition measured by two different dual energy X-ray
absorptiometry devices and three acquisition modes in obese wo-
men. Clin. Nutr. 25: 428–437. doi:10.1016/j.clnu.2005.11.002.
PMID:16375994.
Gray, D.S., Bray, G.A., Gemayel, N., and Kaplan, K. 1989. Effect
of obesity on bioelectrical impedance. Am. J. Clin. Nutr. 50:
255–260. PMID:2756912.
Heymsfield, S.B., and McManus, C.B. 1985. Tissue components of
weight loss in cancer patients: a new method of study and preli-
minary observations. Cancer, 55(Suppl): 238–249. doi:10.1002/
1097-0142(19850101)55:1+<238::AID-CNCR2820551306>3.0.
CO;2-S. PMID:3965090.
Heymsfield, S.B., Smith, R., Aulet, M., Bensen, B., Lichtman, S.,
Wang, J., et al. 1990. Appendicular skeletal muscle mass: mea-
# 2008 NRC Canada
1006
surement by dual-photon absorptiometry. Am. J. Clin. Nutr. 52:
214–218. PMID:2375286.
Heymsfield, S.B., Wang, Z., Baumgartner, R.N., and Ross, R.
1997. Human body composition: advances in models and meth-
ods. Annu. Rev. Nutr. 17: 527–558. doi:10.1146/annurev.nutr.
17.1.527. PMID:9240939.
Isenring, E., Bauer, J., Capra, S., and Davies, P.S.W. 2004. Evalua-
tion of foot-to-foot bioelectrical impedance analysis for the pre-
diction of total body water in oncology outpatients receiving
radiotherapy. Eur. J. Clin. Nutr. 58: 46–51. doi:10.1038/sj.ejcn.
1601744. PMID:14679366.
Kubo, A., and Corley, D.A. 2006. Body mass index and adenocar-
cinomas of the esophagus or gastric cardia: a systematic review
and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 15:
872–878. doi:10.1158/1055-9965.EPI-05-0860. PMID:16702363.
Kyle, U.G., Pichard, C., Rochat, T., Slosman, D.O., Fitting, J.W.,
and Thiebaud, D. 1998. New bioelectrical impedance formula
for patients with respiratory insufficiency: comparison to dual-
energy X-ray absorptiometry. Eur. Respir. J. 12: 960–966.
doi:10.1183/09031936.98.12040960. PMID:9817176.
Kyle, U.G., Bosaeus, I., De Lorenzo, A.D., Deurenberg, P., Elia,
M., Gómez, J.M., et al. 2004a. Bioelectrical impedance anal-
ysis – part I: review of principles and methods. Clin. Nutr. 23:
1226–1243. doi:10.1016/j.clnu.2004.06.004. PMID:15380917.
Kyle, U.G., Bosaeus, I., De Lorenzo, A.D., Deurenberg, P., Elia,
M., Gómez, J.M., et al. 2004b. Bioelectrical impedance analy-
sis – part II: utilization in clinical practice. Clin. Nutr. 23:
1430–1453. doi:10.1016/j.clnu.2004.09.012. PMID:15556267.
Miller, K.D., Jones, E., Yanovski, J.A., Shankar, R., Feuerstein, I.,
and Falloon, J. 1998. Visceral abdominal-fat accumulation asso-
ciated with use of indinavir. Lancet, 351: 871–875. doi:10.1016/
S0140-6736(97)11518-5. PMID:9525365.
Otake, S., Takeda, H., Suzuki, Y., Fukui, T., Watanabe, S.,
Ishihama, K., et al. 2005. Association of visceral fat accumulation
and plasma adiponectin with colorectal adenoma: evidence for
participation of insulin resistance. Clin. Cancer Res. 11: 3642–
3646. doi:10.1158/1078-0432.CCR-04-1868. PMID:15897559.
Prado, C.M.M., Baracos, V.E., McCargar, L.J., Mourtzakis, M.,
Mulder, K.E., Reiman, T., et al. 2007. Body composition as an
independent determinant of 5-fluorouracil-based chemotherapy
toxicity. Clin. Cancer Res. 13: 3264–3268. doi:10.1158/1078-
0432.CCR-06-3067. PMID:17545532.
Prado, C.M.M., Lieffers, J.R., McCargar, L.J., Reiman, T., Sawyer,
M.B., Martin, L., and Baracos, V.E. 2008. Prevalence and clini-
cal implications of sarcopenic obesity in patients with solid tu-
mours of the respiratory and gastrointestinal tracts: a
population-based study. Lancet Oncol., 9: 629–635. doi: 10.
1016/S1470-2045(08)70153-0. PMID: 18439529.
Appl. Physiol. Nutr. Metab. Vol. 33, 2008
Ritchie, J.D., Miller, C.K., and Smicklas-Wright, H. 2005. Tanita
foot-to-foot bioelectrical impedance analysis system validated in
older adults. J. Am. Diet. Assoc. 105: 1617–1619. doi:10.1016/j.
jada.2005.07.011. PMID:16183365.
Ross, R., Dagnone, D., Jones, P.J., Smith, H., Paddags, A.,
Hudson, R., et al. 2000. Reduction in obesity and related co-
morbid conditions after diet-induced weight loss or exercise-
induced weight loss in men. Ann. Intern. Med. 133: 92–103.
PMID:10896648.
Sarhill, N., Walsh, D., Nelson, K., Homsi, J., and Komurcu, S.
2000. Bioelectrical impedance, cancer nutritional assessment,
and ascites. Support. Care Cancer, 8: 341–343. doi:10.1007/
s005209900104. PMID:10923777.
Segal, K.R., Van Loan, M., Fitzgerald, P.I., Hodgdon, J.A., and
Van Itallie, T.B. 1988. Lean body mass estimation by bioelectri-
cal impedance analysis: a four-site cross-validation study. Am. J.
Clin. Nutr. 47: 7–14. PMID:3337041.
Shang, E., Weiss, C., Post, S., and Kaehler, G. 2006. The influence
of early supplementation of parenteral nutrition on quality of life
and body composition in patients with advanced cancer. J.
Parenter. Enteral Nutr. 30: 222–230. doi:10.1177/
0148607106030003222.
Shen, W., Punyanitya, M., Wang, Z., Gallagher, D., St-Onge, M.P.,
Albu, J., et al. 2004a. Total body skeletal muscle and adipose
tissue volumes: estimation from a single abdominal cross-
sectional image. J. Appl. Physiol. 97: 2333–2338. doi:10.1152/
japplphysiol.00744.2004. PMID:15310748.
Shen, W., Punyanitya, M., Wang, Z., Gallagher, D., St-Onge, M.P.,
Albu, J., et al. 2004b. Visceral adipose tissue: relations between
single-slice areas and total volume. Am. J. Clin. Nutr. 80: 271–278.
PMID:15277145.
Simons, J.P.F.H.A., Schols, A.M.W.J., Westerterp, K.R., ten Velde,
G.P.M., and Wouters, E.F.M. 1995. The use of bioelectrical im-
pedance analysis to predict total body water in patients with
cancer cachexia. Am. J. Clin. Nutr. 61: 741–745. PMID:
7702014.
Steiner, M.C., Barton, R.L., Singh, S.J., and Morgan, M.D.L. 2002.
Bedside methods versus dual energy X-ray absorptiometry for
body composition measurement in COPD. Eur. Respir. J. 19:
626–631. doi:10.1183/09031936.02.00279602. PMID:11998990.
Vigano, A., Bruera, E., Jhangri, G.S., Newman, S.C., Fields, A.L.,
and Suarez-Almazor, M.E. 2000. Clinical survival predictors in
patients with advanced cancer. Arch. Intern. Med. 160: 861–868.
doi:10.1001/archinte.160.6.861. PMID:10737287.
von Hafe, P., Pina, F., Perez, A., Tavares, M., and Barros, H. 2004.
Visceral fat accumulation as a risk factor for prostate cancer.
Obes. Res. 12: 1930–1935. doi:10.1038/oby.2004.242. PMID:
15687393.
# 2008 NRC Canada