Content uploaded by Hirokazu Chuman
Author content
All content in this area was uploaded by Hirokazu Chuman on Nov 23, 2015
Content may be subject to copyright.
Prediction of Treatment Outcomes in Patients with Chest Wall
Sarcoma: Evaluation with PET/CT
Yuji Nishiyama1, Ukihide Tateishi1,*, Akira Kawai2, Hirokazu Chuman2, Fumihiko Nakatani2, Mototaka Miyake3,
Takashi Terauchi4, Tomio Inoue1and Edmund E. Kim5
1
Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama,
2
Division of
Orthopedics, National Cancer Center Hospital, Tokyo,
3
Diagnostic Radiology, National Cancer Center Hospital,
Tokyo,
4
Division of Cancer Screening, Research Center for Cancer Prevention and Screening, National Cancer
Center, Tokyo, Japan and
5
Division of Diagnostic Imaging, University of Texas, MD Anderson Cancer Center,
Houston, TX, USA
*For reprints and all correspondence: Ukihide Tateishi, Department of Radiology, Yokohama City University
Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
E-mail: utateish@yokohama-cu.ac.jp
Received May 25, 2012; accepted June 28, 2012
Objective: The aim of this study was to investigate the prognostic implications of
18
F-2-
fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in patients
with chest wall sarcoma.
Methods: Positron emission tomography/computed tomography scans of 42 patients (mean
age: 46 years) with chest wall sarcomas were analyzed. Pathologic confirmation was obtained
by surgical specimens in all patients. Tumor grade assessed by Ki-67 (MIB-1) immunohisto-
chemical analysis and expression of glucose transporter protein 1 were compared with a
maximum standardized uptake value. Univariate and multivariate analyses were conducted
for estimates of overall and event-free survivals.
Results: The median maximum standardized uptake value of the tumor was 10.2 and the
median MIB-1 index of the tumor was 32.5%. Glucose transporter protein 1 expression was
found in 29 patients (69%). Univariate analyses revealed that surgery, chemotherapy, MIB-1
labeling index (cut-off 32.5%), MIB-1 grade, glucose transporter protein 1 expression and
maximum standardized uptake value were possible predictors for overall and event-free sur-
vival. Multivariate analysis revealed that surgery (hazard ratio, 4.852; P¼0.017), maximum
standardized uptake value (hazard ratio, 3.077; P¼0.037) and MIB-1 labeling index (hazard
ratio, 6.549; P¼0.003) were independent predictors of event-free survival. In addition,
surgery (hazard ratio, 4.092; P¼0.021) and maximum standardized uptake value (hazard
ratio, 2.968; P¼0.027) were independent predictors of overall survival.
Conclusions:
18
F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tom-
ography allows the prediction of prognosis after treatment in patients with chest wall sarcoma
and may be useful in selecting high-risk patients for more risk-adapted treatments.
Key words: radiology-PET/CT – orthopedics/sarcoma – prognostic factors
INTRODUCTION
Chest wall sarcomas constitute 15% of all soft tissue sar-
comas that belong to the rare group of unusual primary ma-
lignant mesenchymal tumors that occur in extraskeletal
non-epithelial tissue excluding the viscera, meninges and
lymphoreticular system (1). Chest wall sarcomas can usually
be adequately encompassed by a wide, full-thickness exci-
sion to achieve negative margins. However, the treatment of
chest wall sarcoma has for years consisted of surgical
#The Author 2012. Published by Oxford University Press. All rights reserved.
For Permissions, please email: journals.permissions@oup.com
Jpn J Clin Oncol 2012;42(10)912– 918
doi:10.1093/jjco/hys116
Advance Access Publication 31 July 2012
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
resection, adjuvant chemotherapy and/or radiation therapy.
Attempts have been made to improve treatment by combin-
ation therapy. However, regimens of combination therapy
often fail to improve survival over 3 years (2–4).
Since the biological behavior of soft tissue sarcomas
depends on the histologic grade, soft tissue sarcomas are
graded according to a system on the basis of three histologic
criteria: tumor differentiation, necrosis and MIB-1 (Ki-67)
score. The prognostic significance of histologic type and
grading systems for patients with soft tissue sarcomas were
investigated previously in a large series (5,6).
Chest wall sarcomas are typically evaluated by conven-
tional imaging including magnetic resonance imaging (MRI)
of the primary site, chest radiograph or chest computed tom-
ography (CT) and bone scintigraphy (7). Evaluation of MRI
is predominantly focused on determining the extent of tumor
involvement and the potential for resectability. Chest radio-
graph or CT and bone scintigraphy are useful to detect bone
involvement or distant metastasis prior to treatment.
Accurate imaging evaluation of tumor extent provides critic-
al anatomic information for planning both the surgical ap-
proach and the treatment field for adjuvant radiation therapy.
Positron emission tomography (PET) using 2-fluoro-2-
deoxy-D-glucose (
18
F-FDG) has been used to evaluate the
prognosis in patients with soft tissue sarcomas (8–12).
18
F-FDG uptake expressed semi-quantitatively by the stan-
dardized uptake value (SUV) has been strongly associated
with prognosis (13,14). The degree of
18
F-FDG uptake in
soft tissue sarcomas is associated with histological tumor
aggressiveness and glucose transporter protein 1 (Glut-1) ex-
pression (15,16). Identification of PET findings affecting
disease prognosis in chest wall sarcoma may be useful to de-
termine the pre-operative value. However, despite the in-
creasing use of PET/CT in the management of soft tissue
sarcomas, no study to date has assessed the prognostic impli-
cation of PET/CT in patients with chest wall sarcomas. The
aim of this study was to investigate the prognostic value of
18
F-FDG PET/CT in patients with chest wall sarcoma.
PATIENTS AND METHODS
PATIENTS
From December in 2004 to June in 2008, a total of 42
patients were identified who had a clinical diagnosis of chest
wall sarcoma at the time of their initial referral to our institu-
tion. The definition of chest wall sarcoma was extraskeletal
sarcoma arising from the thoracic cage. This study was per-
formed with the approval of the institutional review board.
The clinical details, including physical examinations and
follow-up information were obtained by reviewing all the
medical charts. A retrospective chart review examined the
following data elements: patient age; gender; presenting
symptom; history of previous radiation therapy for another
malignancy; tumor size and the use of adjuvant chemother-
apy or radiation therapy. Twenty-eight of the 42 patients
weremen(67%)and14werewomen(33%).Theirmean
age at diagnosis was 46 years (range, 20–78 years). None of
the patients had previous or coexistent systemic diseases.
Complete surgical resection of the primary site was per-
formed in 19 patients (45%) and incomplete surgical resec-
tion was performed in 16 (38%). Incisional biopsy was
performed in seven patients (17%). Depending on the histo-
logic diagnosis, stage and site of the presentation, patients
were given either adjuvant chemotherapy alone or a combin-
ation of adjuvant chemotherapy and radiotherapy. The ma-
jority of patients (n¼19) received ifosfamide, cisplatin,
adriamycin and etoposide in standard doses. Patients with
Ewing sarcoma (n¼2) received vincristine, ifosfamide and
etoposide. Patients with rhabdomyosarcoma (n¼2) received
vincristine, adriamycin and cyclophosphamide. Radiotherapy
was given with megavoltage energies using an involved field
technique to tumor doses of 30 – 36 Gy in daily fractions of
1.8– 2.0 Gy. Patients were clinically followed until the end
of December 2011 at which time 21 patients (50%) were
alive with no evidence of disease, 4 (10%) were alive with
disease and 17 (40%) had died of their disease. No patients
were lost at the follow-up, which began on the date of
primary surgery. The mean duration of follow-up was 32.6
months (1.3 – 84.6 months). Patient status (alive or dead) and
disease status (free of disease, development of local recur-
rence or development of distant metastasis) were recorded.
IMAGING STUDIES
All PET/CT scans were obtained before biopsy or treatments.
Scans were acquired with PET/CT device (Aquiduo
PCA-7000B; Toshiba Medical Systems, Tokyo, Japan). We
used a NEMA image quality phantom (NU 2–2001) for
cross calibration (17). The radioactivity concentration of the
background was set at 2.6 +0.2 kBq/ml of
18
F-FDG, similar
to that in the clinical condition. Acquired data, including the
normalization data, cross-calibration data, blank scan data
and transmission data were assessed for visual inspection,
phantom noise equivalent count (NEC
phantom
), % contrast
(Q
H,10 mm
) and % background variability (N
10 mm
). The pre-
ferred parameters pertinent to the clinical condition were
NEC
phantom
.10.4 (Counts), N
10 mm
,6.2% and Q
H,10 mm
/
N
10 mm
.1.9%. After a review of the data analyses, the
optimum conditions for the PET/CT were also determined:
data acquisition, 180 s for one bed; FOV, 500 mm; iteration,
4; subset, 14; matrix size,128 128; filter, Gaussian 8 mm
in FWHM; reconstruction, attenuation-weighted ordered-
subsets expectation maximization.
Prior to the PET/CT study, the patients fasted for at least
6 h. CT was performed from the head to the thigh according
to a standardized protocol with the following setting: axial
3.0-mm collimation 16 modes; 120 kVp; 80 mAs and a
0.5-s tube rotation. Emission scans from the base of the skull
to the mid-thigh were obtained starting 55 – 60 min after the
intravenous administration of 370 MBq of
18
F-FDG.
Jpn J Clin Oncol 2012;42(10) 913
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
The images were reviewed and a diagnostic consensus
was reached by a board-certified radiologist and a nuclear
medicine specialist who were unaware of any clinical or
radiologic information using a multimodality computer plat-
form. PET and co-registered PET/CT images were analyzed
with dedicated software (Vox-base SP1000 workstation,
J-MAC systems, Sapporo, Japan). A volume of interest was
outlined in the peak activity within regions of increased
18
F-FDG uptake. The SUV was calculated according to the
following equation: SUV ¼maximal count calibration
factor (kBq/ml)/injected activity (MBq)/body weight (kg).
When the tumor is extensively heterogeneous, the VOIs
were set to cover all the components of the tumor.
HISTOPATHOLOGICAL ANALYSIS
The mean time interval between PET/CT study and surgical
resectionorbiopsywas7days(range,1–13days).
Pathologic specimens of all tumors were obtained by surgi-
cal resection or biopsy. Histological slides of all the patients’
tumors were reviewed for diagnosis by an expert pathologist.
Slices with a thickness of 4 mm were cut, stained with hema-
toxylin– eosin and examined with light microscopy.
Whenever necessary, immunohistochemical staining was
carried out to confirm the diagnosis or tumor type according
to the World Health Organization classification (18). Tumor
specimens were immunostained with the antibody Ki-67
(clone MIB-1; DakoCytomation; diluted 1:100 and auto-
claved) and the Ki-67 (MIB-1) labeling index (LI) was esti-
mated by calculating the percentage of Ki-67 positive cell
nuclei among 1000 tumor cells in the region of the tumor in
which the greatest density of MIB-1 staining was observed
under a light microscope. An MIB-1 score of 1 was assigned
to the lesions with an MIB-1 LI of 0–9%, an MIB-1 score
of2wasgiventolesionswithanMIB-1LIof10–29%and
an MIB-1 score of 3 was given to lesions with an MIB-1 LI
30%. In this study, the histological grade of a tumor was
determined using a grade system established by Hasegawa
et al. (5,6). This histological grade is a three-grade system
obtained by adding the scores for tumor differentiation,
tumor necrosis and MIB-1 score, each of which was given a
score of 0–3. According to this grading system, all chest
wall sarcomas were assigned MIB-1 grades 1 – 3. Tumors
were also graded by the Fe
´de
´ration Nationale des Centres du
Lutte Contre le Cancer (FLCNCC) grading system. For
Glut-1 immunostaining, the primary antibody applied was an
affinity-purified goat polyclonal antibody (A3536; Dako;
diluted 1:500). The intensity of Glut-1 staining was quanti-
fied with regard to the percentage of cells stained. Intensity
of Glut-1 staining was scored as 0 (0%), 1 (1 –9%), 2 (10 –
29%) or 3 (.30%). The intensity of Glut-1 staining was
reviewed by an expert pathologist unaware of the clinical in-
formation. Each tumor was staged according to the TNM
classification of the Union for International Cancer Control
(UICC) for sarcoma of bone and the American Joint
Committee on Cancer (AJCC) staging protocol for sarcoma
of the soft tissue. PET/CT images were assessed in consen-
sus by a board-certified radiologists and a nuclear medicine
specialist who were aware of clinical information.
STATISTICAL ANALYSIS
Survival was calculated for two-dependent endpoints. The
primary endpoint was the overall survival that was defined as
the time in month from the date of primary surgery until the
date the patient was last known to be alive. Any death from
any cause was considered a failure. The event-free survival
was the secondary time-dependent endpoint. This was
defined from the date of primary surgery to the date of
pathological confirmation or the date of identification of re-
current disease on conventional imaging studies. Univariate
analysis was performed by comparing Kaplan–Meier sur-
vival curves and carrying out log-rank tests. Factors analyzed
for prognostic significance included the following: patient
age; gender; tumor size; the use of adjuvant chemotherapy;
the use of radiation therapy; surgery (complete, incomplete
or incisional biopsy); MIB-1 index; MIB-1 grade; FLCNCC
grade; Glut-1 expression and SUV
max
. The hazard ratio of
each variable subjected to multivariate analysis was esti-
mated using a Cox proportional hazards model. The relation-
ships between MIB-1 index, MIB-1 grade, FLCNCC grade,
Glut-1 intensity and SUV
max
were assessed by Pearson’s
rank correlation test. Statistical analysis was performed with
the PASW Statistics 19 software program (IBM, Tokyo,
Japan). Differences and correlations at a Pvalue of ,0.05
were considered to be statistically significant.
RESULTS
The baseline demographic data are shown in Table 1.The
median age of patients was 44 years. No significant differ-
ences were seen in age and gender. The median size of the
primary site was 62 mm (range, 20– 225 mm). T stage was
T1a (n¼9, 21), T1b (n¼3, 7), T1 (n¼1, 2), T2a (n¼3,
7), T2b (n¼23, 55) and T2 (n¼3, 7%). The lesions were
identified at histologic analysis as liposarcoma (26%), pleo-
porphic malignant fibrous histiocytoma (21%), myxofibrosar-
coma (12%), synovial sarcoma (12%), chondrosarcoma
(10%), Ewing sarcoma (5%), rhabdomyosarcoma (5%),
osteosarcoma (5%), dermatofibrosarcoma protuberans (2%)
and alveolar soft part sarcoma (2%). The median MIB-1
index of tumor was 32.5%. MIB-1 grades were grade 1 (n¼
10, 24), grade 2 (n¼2, 5) and grade 3 (n¼30, 71%), re-
spectively. FLCNCC grades were grade 1 (n¼5, 12), grade
2(n¼18, 43) and grade 3 (n¼19, 45%), respectively.
Glut-1 expression was found in 32 patients (76%) and their
intensities were 1 (n¼3, 9), 2 (n¼5, 16%) and 3 (n¼24,
75%). Glut-1 immunostaining was absent in 10 tumors: five
well-differentiated liposarcomas, two myxoid liposarcomas,
two myxofibrosarcomas and one dermatofibrosarcoma protu-
berans. The median SUV
max
of the tumor was 10.2 (range,
914 PET/CT evaluation of chest wall sarcoma
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
0.7– 16.6). Tumor stage was IA (n¼8, 19%), IB (n¼3,
7%), IIA (n¼5, 12%), IIB (n¼3, 7%) and III (n¼23,
55%). There were statistically significant correlations
between SUV
max
, MIB-1 grade, Glut-1 expression and
MIB-1 LI (Table 2).
Table 3illustrates the univariate analysis of the prognostic
influence of co-variables on event-free survival. Age,
gender, size, surgery, chemotherapy and radiotherapy had no
prognostic value. Complete resection (P¼0.017) and the
absence of chemotherapy (P¼0.001) were possible predic-
tors of event-free survival. Patients with a SUV of ,10.2
had significantly longer event-free survival (P,0.0001)
than did those with a SUV
max
10.2 (Fig. 1). In the patho-
logic examinations, MIB-1 LI (P,0.0001), MIB-1 grade
Table 2. The correlations between maximum standardized uptake value,
glucose transporter protein 1 expression, MIB-1 grade, MIB-1 labeling
index and FNCLCC grade
SUV
max
Glut-1
expression
MIB-1
grade
MIB-1
labeling
index
FNCLCC
grade
SUV
max
– 0.685 0.476 0.660 0.413
Glut-1
expression
– – 0.607 0.876 0.685
MIB-1 grade – – – 0.632 0.437
MIB-1
labeling
index
– – – – 0.699
FNCLCC
grade
–– – – –
Note: all the correlations were evaluated by Pearson’s rank correlation test
(P,0.05). FNCLCC, Fe
´de
´ration Nationale des Centres du Lutte Contre le
Cancer (FLCNCC).
Table 3. Univariate analysis of event-free survival after treatment
Variables Criteria n5 year (%) Pvalue
Age ,44 26 (62) 44.4 0.455
44 16 (38) 52.1
Gender Female 15 (36) 66.7 0.143
Male 27 (64) 37.7
Size ,62 21 (50) 63.5 0.06
62 21 (50) 31.7
Surgery Complete 19 (45) 72.4 0.017
Incomplete 16 (38) 18.8
Biopsy 7 (17) 28.6
Chemotherapy 219 (45) 75.8 0.001
þ23 (55) 23.5
Radiation 230 (71) 51.6 0.466
þ12 (29) 41.7
MIB-1 labeling index ,32.5 21 (50) 81.0 ,0.0001
32.5 21 (50) 11.1
MIB-1 grade 1 or 2 12 (29) 91.7 0.001
3 30 (71) 23.2
Glut-1 expression 213 (31) 91.7 ,0.0001
þ29 (69) 22.6
FLCNCC grade 1 or 2 23 (55) 55.7 0.012
3 19 (45) 0.0
SUV
max
,10.2 22 (52) 69.3 ,0.0001
10.2 20 (48) 25.0
Note: the numbers in parentheses are percentages.
Table 1. Patient demographics
Age
Mean +SD 46 +17
Range 20– 78
Gender
Male/female 28/14
Size (mm)
Mean +SD 79 +50
Range 20– 225
Histology
Liposarcoma 11 (26)
Well-differentiated 5 (12)
Myxoid 3 (7)
Dedifferentiated 3 (7)
Pleomorphic MFH 9 (21)
Myxofibrosarcoma 5 (12)
Synovial sarcoma 5 (12)
Chondrosarcoma 4 (10)
Ewing sarcoma 2 (5)
Rhabdomyosarcoma 2 (5)
Osteosarcoma 2 (5)
Dermatofibrosarcoma protuberans 1 (2)
Alveolar soft part sarcoma 1 (2)
Tumor grade
Low 10 (24)
Intermediate 2 (5)
High 30 (71)
Surgery
Complete 19 (45)
Incomplete 16 (38)
Biopsy 7 (17)
Note: the numbers in parentheses are percentages. MFH, malignant fibrous
histiocytoma.
Jpn J Clin Oncol 2012;42(10) 915
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
(P¼0.001), FNCLCC grade (P¼0.012) and Glut-1 expres-
sion (P,0.0001) were associated with a trend toward
longer event-free survival.
Table 4illustrates the univariate analysis of the prognostic
implication of co-variables on overall survival. Complete re-
section was a possible predictor of overall survival (P¼
0.002, Fig. 1). Patients who did not receive chemotherapy
showed longer overall survival than those who received
chemotherapy (P,0.0001). Overall survival did not differ
significantly whether radiation therapy was performed or
not. Age, gender, size and surgery were not linked to overall
survival. Patients showing SUV
max
of ,10.2 had also sig-
nificantly longer overall survival (P,0.001) than those with
SUV
max
levels 10.2 (Fig. 2). MIB-1 LI (P,0.0001,
Fig. 3), MIB-1 grade (P,0.0001) and Glut-1 expression
(P,0.0001) were associated with a trend toward longer
overall survival.
When analysis was confined to multivariate analysis,
surgery (P¼0.017), MIB-1 LI (P¼0.003) and SUV
max
(P¼0.037) were independently associated with longer event-
free survival (Table 5). However, chemotherapy, MIB-1 grade
and Glut-1 expression were not independently associated with
event-free survival. Multivariate analysis revealed that surgery
(P¼0.021) and SUV
max
(P¼0.027) were independently
associated with longer overall survival (Table 6).
Chemotherapy, MIB-1 grade, MIB-1 LI and Glut-1 expression
failed to show any association with overall survival.
DISCUSSION
The aim of this study was to assess the prognostic implica-
tions of PET/CT findings in patients with chest wall sarco-
mas. The results are notable for three features. First, surgery,
chemotherapy, MIB-1 LI, Glut-1 expression, MIB-1 grade
and SUV
max
were possible prognostic factors in the univari-
ate analysis. Second, surgery and SUV
max
were independent-
ly associated with both overall and event-free survivals in
the multivariate analyses. And third, there were significant
Figure 2. A 71-year-old man with pleomorphic malignant fibrous histiocy-
toma of the chest wall. An axial positron emission tomography/computed
tomography (PET/CT) image demonstrates a soft tissue mass (arrow) of the
anterior chest wall with a maximum SUV of 12.8. On pathologic examin-
ation, the tumor shows the MIB-1 labeling index of 50%, Glut-1 intensity of
3 and MIB-1 grade of 3.
Figure 1. A 71-year-old woman with myxoid liposarcoma of the chest wall.
An axial PET/CT image demonstrates a soft tissue mass (arrow) of the an-
terior chest wall with a maximum SUV of 3.5. The tumor shows the MIB-1
labeling index of 5%, Glut-1 negative and MIB-1 grade of 1 on pathologic
examination.
Table 4. Univariate analysis of overall survival after treatment
Variables Criteria n5 year (%) Pvalue
Age ,44 26 (62) 37.0 0.557
44 16 (38) 29.8
Gender Female 15 (36) 40.0 0.219
Male 27 (64) 31.4
Size ,62 21 (50) 47.2 0.099
62 21 (50) 25.4
Surgery Complete 19 (45) 67.2 0.002
Incomplete 16 (38) 14.1
Biopsy 7 (17) 0.0
Chemotherapy 219 (45) 64.6 ,0.0001
þ23 (55) 0.0
Radiation 230 (71) 43.1 0.177
þ12 (29) 16.7
MIB-1 labeling index ,32.5 21 (50) 57.7 ,0.0001
32.5 21 (50) 11.1
MIB-1 grade 1 or 2 12 (29) 91.7 ,0.0001
3 30 (71) 0.0
Glut-1 expression 213 (31) 91.7 ,0.0001
þ29 (69) 0.0
FCLCC grade 1 or 2 23 (55) 59.4 0.236
3 19 (45) 0.0
SUV
max
,10.2 22 (52) 58.0 ,0.0001
10.2 20 (48) 13.3
Note: the numbers in parentheses are percentages.
916 PET/CT evaluation of chest wall sarcoma
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
correlations between MIB-1 LI, Glut-1 expression, MIB-1
grade and SUV
max
. Therefore, we confirm that PET/CT is a
non-invasive method for evaluating patients’ prognosis after
treatment in soft tissue sarcomas as reported in the previous
studies (13,14). This study is stratified by chest wall sarco-
mas that are characterized as difficult tumors for complete
control regardless of combination therapy. To our knowl-
edge, this report is the first to describe the prognostic impli-
cations of PET/CT for chest wall sarcomas.
The use of semi-quantification as the technique for inter-
preting PET is generally conducted in studies of soft-tissue
sarcoma (13,14). Semi-quantification of PET is helpful in
defining the minimal uptake category and is a more objective
way to interpret therapeutic response compared with visual
analysis alone. Since
18
F-FDG uptake is a continuous vari-
able, a dichotomous variable such as visual analysis is sub-
jective and hard to interpret in some situations. In addition,
investigators should be attentive to regulate scan parameters
in advance because there is variability among PET equip-
ment. Therefore, we had conducted a phantom study to de-
termine optimal scan parameters fitted prior to clinical study.
The SUV
max
was used for semi-quantitative measurement
of
18
F-FDG accumulation to assess tumor viability in our
study. The median SUV
max
of 10.2 proved to be a significant
cut-off value for the purpose of predicting overall and event-
free survivals in the univariate analysis. Tumors with
SUV
max
greater than the median SUV
max
show poorer
overall and disease-free survivals than those with SUV
max
below the median SUV
max
. Although our study population
has a tendency to high-grade chest wall sarcomas, SUV
max
clearly reflects tumor aggressiveness.
In our study, SUV
max
is associated with the overall and
the event-free survivals in the univariate analysis. Whether
PET/CT finding is more predictive of overall and event-free
survivals than other variables is unknown and may require
an investigation within a much larger trial. However,
SUV
max
correlates with the intensity of Glut-1 expression in
our study. The enhanced metabolic response in chest wall
sarcomas is characterized by an increased Glut-1 staining in-
tensity. The results of the present study may appear to be
consistent with our preliminary analysis for bone and soft
tissue sarcomas (15).
Glut-1 expression is the common mediator of glucose
uptake in malignant tumors. Glut-1 expression is also asso-
ciated with the overall and the event-free survivals in the
univariate analysis in the present study. However, there were
four Glut-1-negative tumors with
18
F-FDG uptake. Glucose
transporter proteins other than Glut-1 exist and express in
Figure 3. Kaplan –Meier estimates of overall survival (a) and event-free
survival (b) according to maximum standardized uptake value (SUV
max
).
Solid line: SUV
max
,10.2; dash line: SUV
max
10.2. Tumors with SUV
max
,10.2 show a longer overall and event-free survivals than those with
SUV
max
10.2.
Table 5. Multivariate analysis of event-free survival after treatment
Variables Hazard ratio 95% CI Pvalue
Surgery 4.852 1.327– 17.743 0.017
MIB-1 labeling index 6.549 1.890–22.691 0.003
SUV
max
3.077 1.067– 8.873 0.037
CI, confidence interval.
Table 6. Multivariate analysis of overall survival after treatment
Variables Hazard ratio 95% CI Pvalue
Surgery 4.092 1.232– 13.598 0.021
SUV
max
2.968 1.132– 7.780 0.027
Jpn J Clin Oncol 2012;42(10) 917
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
various histologic kinds of malignant tumors (19). It is pos-
sible that Glut-1-negative tumors would have been positive
for other glucose transporters.
In our study, PET/CT scans were performed prior to inci-
sional biopsy. Although evaluation of PET/CT resulted in no
patient with distant metastasis in our study, the assessment
prior to biopsy may reveal unexpected distant metastasis.
When a suspected lesion for distant metastasis is found by
whole body PET/CT, the course of therapy may have to be
changed. Incisional biopsy is essential to diagnose chest wall
sarcomas for histopathologic tissue assays, but incisional
biopsy provides local biological information about the tumors.
The limitation of our study is the limited number of
patients and follow-up duration. Whether PET/CT findings
add original information to several prognostic variables
requires a further evaluation in an ongoing long-term study
with a large patient population. MIB-1 LI has a good prog-
nostic significance in the multivariate analysis. This finding
to some extent validates our study population because
MIB-1 LI is an excellent indicator of tumor grade and one
of the most important prognostic factors in patients with soft
tissue sarcomas treated with combination therapy (5,6).
However, MIB-1 grade was not independently associated
with poor prognosis in our study. The small numbers of
patients in our study may affect the results of the multivari-
ate analysis. Treatment regimens and duration were not the
same for all the patients. Since combination therapy in our
study is eligible for patients with high-grade tumors, this
might be biased with the study analysis.
In summary, our results, obtained in a heterogeneous
population of chest wall sarcomas, confirm that patients re-
ceiving incomplete resection or patients showing high
SUV
max
may be associated with poor prognosis after treat-
ment. These findings support the concept of pre-therapeutic
stratification with
18
F-FDG PET/CT imaging to identify
high-risk patients and we propose a more risk-adapted treat-
ment approach in patients with chest wall sarcoma.
Funding
This work was supported in part by grants from Scientific
Research Expenses for Health and Welfare Programs, No.
17– 12, the promotion and standardization of diagnostic ac-
curacy in PET/CT imaging, the Grant-in-Aid for Cancer
Research from the Ministry of Health, Labour and Welfare
and Travel Grant of the Princess Takamatsu Cancer
Research Fund.
Conflict of interest statement
None declared.
References
1. Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s Soft Tissue
Tumours. 4th edn. St. Louis: Mosby 2001.
2. Walsh GL, Davis BM, Swisher SG, et al. A single-institutional,
multidisciplinary approach to primary sarcomas involving the chest wall
requiring full-thickness resections. J Thorac Cardiovasc Surg
2001;121:48– 60.
3. Athanassiadi K, Kalavrouziotis G, Rondogianni D, Loutsidis A,
Hatzimichalis A, Bellenis I. Primary chest wall tumors: early and
long-term results of surgical treatment. Eur J Cardiothorac Surg
2001;19:589– 93.
4. Shamberger RC, LaQuaglia MP, Gebhardt MC, et al. Ewing sarcoma/
primitive neuroectodermal tumor of the chest wall: impact of initial
versus delayed resection on tumor margins, survival, and use of
radiation therapy. Ann Surg 2003;238:563 – 7.
5. Hasegawa T, Yamamoto S, Yoko yama R, Umeda T, Matsuno Y,
Hirohashi S. Prognostic significance of grading and staging system
using MIB-1 score in adult patients with soft tissue sarcoma of the
extremities and trunk. Cancer 2002;95:843– 51.
6. Hasegawa T, Yamamoto S, Nojima T, et al. Validity and reproducibility
of histologic diagnosis and grading for adult soft-tissue sarcomas. Hum
Pathol 2002;33:111– 5.
7. Tateishi U, Gladish GW, Kusumoto M, et al. Chest wall tumors:
radiologic findings and pathologic correlation: part 2. Malignant tumors.
Radiographics 2003;23:1491– 508.
8. Nieweg OE, Prium J, van Ginkel RJ, et al. Fluorine-18
fluorodeoxyglucose PET imaging of soft-tissue sarcoma. JNuclMed
1996;37:257– 61.
9. Schwarzbach MHM, Dimitra kopoulou -Strauss A, Wil leke F, e t al.
Clinical value of [18-F] fluorodeoxyglucose positron emission
tomography imaging in soft tissue sarcomas. Ann Surg 2000;231:
380–6.
10. Fary JF, Conrad EU, Bruckner JD, et al. Quantitative
[F-18]fluorodeoxyglucose positron emission tomography in pretreatment
and grading of sarcoma. Clin Cancer Res 1998;4:1214– 20.
11. Ioannidis JP, Lau J.
18
F-FDG PET for the diagnosis of soft tissue
sarcoma: a meta-analysis. J Nucl Med 2003;44:717– 24.
12. Bastiaannet E, Groen H, Jager PL, et al. The value of FDG-PET in the
detection, grading and response to therapy of soft tissue and bone
sarcomas: a syste matic review and meta- analysis. Cancer Treat Rev
2004;30:83– 101.
13. Folpe AL, Lyles RH, Sprouse JT, Conrad EU, III, Eary JF. (F-18)
fluorodeoxyglucose positron emission tomography as a predictor of
pathologic grade and other prognostic variables in bone and soft tissue
sarcoma. Clin Cancer Res 2000;6:1279– 87.
14. Benz RM, Czernin J, Allen-Auerbach MS, et al. FDG-PET/CT imaging
predicts histopathologic treatment responses and after the initial cycle of
neoadjuvant chemotherapy in high-grade soft-tissue sarcomas. Clin
Cancer Res 2009;15:2856– 63.
15. Tateishi U, Yamaguchi U, Seki K, Terauchi T, Arai Y, Hasegawa T.
Glut-1 expression and enhanced glucose metabolism are associated with
tumor grade in bone and soft tissue sarcomas: a prospective evaluation
by [18F]fluorodeoxyglucose positron emission tomography. Eur J Nucl
Med Mol Imaging 2006;33:683–91.
16. Ito S, Nemoto T, Satoh S, Sekihara H, Seyama Y, Kubota S. Human
rhabdomyosarcoma cells retain insulin-regulated glucose transport
activity through glucose transporter 1. Arch Biochem Biophys
2000;3:72– 82.
17. Fukukita H, Senda M, Terauchi T, et al. Japanese guideline for the
oncology FDG-PET/CT data acquisition protocol: synopsis of Version
1.0. Ann Nucl Med 2010;24:325– 34.
18. Fletcher CDM, Unni KK, Mertens F, editors. World Health
Organization Classification of Tumours. Pathology and Genetics of
Tumours of Soft Tissue and Bone. Lyon, France: IARC Press
2002.
19. Medina RA, Owen GI. Glucose transporters: expression, regulation and
cancer. Biol Res 2002;35:9– 26.
918 PET/CT evaluation of chest wall sarcoma
by guest on October 27, 2015http://jjco.oxfordjournals.org/Downloaded from
