You are on page 1of 8

Comparison of PET/CT and MRI for the detection of bone marrow invasion in

patients with squamous cell carcinoma of the oral cavity


Yasser G. Abd El-Hafez
a,b
, Chien-Cheng Chen
c
, Shu-Hang Ng
c
, Chien-Yu Lin
d
, Hung-Ming Wang
e
,
Sheng-Chieh Chan
a
, I-How Chen
f
, Shiang-Fu Huan
f
, Chung-Jan Kang
f
, Li-Yu Lee
g
, Chih-Hung Lin
h
,
Chun-Ta Liao
f,
, Tzu-Chen Yen
a,
a
Nuclear Medicine Department, Molecular Imaging Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
b
Radiotherapy and Nuclear Medicine Department, South Egypt Cancer Institute, Assiut University, Egypt
c
Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
d
Department of Radiation Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
e
Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
f
Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
g
Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
h
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC
a r t i c l e i n f o
Article history:
Received 24 December 2010
Received in revised form 11 February 2011
Accepted 11 February 2011
Keywords:
Bone invasion
Oral cancer
Mandible
Maxilla
Squamous cell carcinoma
Positron emission tomography (PET)/
computed tomography (CT)
Fluorodeoxyglucose
Magnetic resonance imaging
s u m m a r y
Our aim was to retrospectively assess the diagnostic performance from combined positron emission
tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the detection
of bone marrow invasion of the mandible or maxilla in patients with oral cavity squamous cell carcinoma
(OCSCC).
A total of 114 patients with OCSCC, arising from or abutting the upper or lower alveolar ridge, under-
went staging PET/CT and MRI studies before surgery. The possibility of bone marrow invasion on PET/CT
and MRI was graded retrospectively on a 5-point score. Histopathology was taken as the reference stan-
dard. Sensitivity, specicity, predictive values and likelihood ratios were calculated. Clinical factors
affecting the performance, like tumor origin and dentate status were also explored.
PET/CT was found to be more specic than MRI (83% vs. 61%, respectively, p = 0.0015) but less sensitive
(78% vs. 97%, respectively, p = 0.0391). Dentate status and tumor origin affected the diagnostic perfor-
mance of PET/CT. In patients with positive MRI, sensitivity and specicity of PET/CT were 78% and
100% in dentate patients with alveolar ridge tumors, 75% and 80% in dentate patient with buccal tumors,
90% and 33% in edentulous patients with alveolar ridge tumors and 0% and 63% for edentulous patients
with buccal tumors, respectively.
PET/CT is more specic than MRI and can be used to complement the role of MRI. A negative MRI result
can condently exclude the presence of bone marrow invasion, while in patients with positive MRI nd-
ings, a negative PET/CT may be useful to rule out bone marrow invasion in dentate patients.
2011 Elsevier Ltd. All rights reserved.
Introduction
The preoperative detection of bone marrow invasion involving
both the maxilla and mandible in patients with squamous cell
carcinoma of the oral cavity (OCSCC) is critical to the planning of
surgery and postoperative management. It is accepted that when
the mandibular bone marrowis free of tumor, mandibular continu-
ity can usually be preserved and a marginal mandibulectomy may
be oncologically sufcient for minimal cortical erosion.
1,2
However,
once bone marrow invasion has occurred, a much more extensive
and lengthy operation involving segmental mandibulectomy plus
bone reconstruction is necessary to provide an adequate clear bony
margin.
3,4
When tumor invades the maxillary marrow spaces,
greater resection margin and extensive reconstruction may be
required.
Computed tomography (CT) and magnetic resonance imaging
(MRI) are the standard modalities used to evaluate primary tumor
status in patients with OCSCC. In general, MRI is preferred because
of its superior soft-tissue contrast resolution,
5
but its diagnostic
accuracy in the detection of bone marrow invasion is still a matter
of debate.
611
Indeed, few past studies have shown high sensitivity
1368-8375/$ - see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.oraloncology.2011.02.010

Corresponding authors. Address: Department of Otorhinolaryngology, Head and


Neck Surgery, Head and Neck Oncology Group, Chang Gung Memorial Hospital,
Chang Gung University, 5 Fu-Hsin Street, Gweishan, Taoyuan 333, Taiwan, ROC.
Tel.: +886 3 328 1200x8466; fax: +886 3 211 0052 (C.-T. Liao). Department of
Nuclear Medicine, Molecular Imaging Center, Chang Gung Memorial Hospital,
Chang Gung University, 5 Fu-Hsin Street, Gweishan, Taoyuan 333, Taiwan, ROC.
Tel.: +886 3 328 1200x2744; fax: +886 3 211 0052 (T.-C. Yen).
E-mail addresses: liaoct@adm.cgmh.org.tw (C.-T. Liao), yen1110@adm.cgmh.
org.tw (T.-C. Yen).
Oral Oncology 47 (2011) 288295
Contents lists available at ScienceDirect
Oral Oncology
j our nal homepage: www. el sevi er . com/ l ocat e/ or al oncol ogy
and specicity,
10,11
whereas others demonstrated high sensitivity
but low specicity.
69
The preoperative detection of bone marrow invasion may be
theoretically enhanced with the use of combined positron emission
tomography (PET)/CT imaging that detects metabolic anomalies
via differences in tissue glucose uptake. However, relatively few
studies have addressed this question.
1215
The purpose of our study
was therefore to assess and compare the diagnostic accuracy of
PET/CT and MRI in detecting bone marrow invasion involving both
the maxilla and mandible in patients with OCSCC and also to ex-
plore possible clinical factors, which might affect the performance
of these modalities.
Materials and methods
Patients
This retrospective study was approved by the Institutional
Review Board at our hospital, and all patients provided written in-
formed consent. The study population consisted of 114 patients
with newly diagnosed OCSCC who were referred to our hospital
between June 2006 and December 2009. Inclusion criteria were a
diagnosis of SCC, originating from the alveolar ridge (upper or low-
er) or other oral cavity subsites but involving the alveolar ridge,
preoperative PET/CT and MRI staging studies and surgical manage-
ment. All patients underwent marginal or segmental mandibulec-
tomy, either with or without inferior maxillectomy. Segmental
mandibulectomy was performed in the presence of: (a) bone mar-
row invasion detected by conventional modalities (CT/MRI and
orthopantogram); (b) an edentulous atrophic mandible; and (c) tu-
mors close to the mandible precluding a marginal resection. Tumor
margins were sent for frozen section. If frozen section margins
were positive, additional tissue was excised and sent for frozen
section in order to ensure that margins were tumor-free. The sur-
gical defects were repaired with primary closure or reconstructed
by free or local aps. Patients were classied as edentulous if they
lost one or more tooth at the site of the tumor, either the upper or
lower alveolar ridge, as seen in the immediate post-surgical
specimens.
Histopathology
The surgical specimens were xed in 10% formalin solution and
decalcied for a period of one day. Specimens were inked and soft
tissue was removed to grossly evaluate the bone. In the presence
of gross bone invasion, a representative 5 mm section of the
bonetumor interface was prepared. In the absence of gross inva-
sion, 2 sections (5 mm each) were taken from the site with the
deepest tumor invasion. All sections were H&E stained in 5 lm
thickness and reviewed by a single pathologist who was aware of
the clinical staging.
Table 1
General characteristics of the study participants.
Parameter n %
Sex
Male 2 (1.8)
Female 112 (98.2)
Age, years
Median (range)
a
50 (2977)
Anatomical subsites
Tongue 6 (5.3)
Floor of the mouth 6 (5.3)
Buccal 47 (41.2)
Alveolar ridge 39 (34.2)
Hard palate 2 (1.8)
Retromolar trigone 14 (12.3)
Dentate status
Dentate 64 (56.1)
Edentulous 50 (43.9)
Metal-related artifacts
No 53 (46.5)
Yes 61 (53.5)
Clinical T-status
T1 3 (2.6)
T2 34 (29.8)
T3 15 (13.2)
T4 62 (54.4)
Pathological T-status
T1 3 (2.6)
T2 38 (33.3)
T3 14 (12.3)
T4 59 (51.8)
Pathological bone marrow invasion
No 77 (67.5)
Yes 37 (32.5)
Site of marrow invasion
Mandible 34 (29.8)
Maxilla 2 (1.8)
Both 1 (0.9)
Bone management
MM
b
16 (14)
SM
c
36 (31.6)
MM + MX
d
36 (31.6)
SM + MX 26 (22.8)
a
The numbers in parentheses indicate the range of the data. Unless otherwise
indicated, values are given as numbers of patients (percentages in parentheses).
b
Marginal mandibulectomy.
c
Segmental mandibulectomy.
d
Maxillectomy.
Table 2
Diagnostic performances of PET/CT and MRI for the detection of bone marrow invasion in patients with squamous cell carcinoma of the oral cavity.
Imaging modality FN
a
TP
b
TN
c
FP
d
Total Sensitivity
(95% CI
e
)
Specicity
(95% CI
e
)
PPV
f
(95% CI
e
)
NPV
g
(95% CI
e
)
Accuracy
(95% CI
e
)
LR+
h
(95% CI
e
)
LR
i
(95% CI
e
)
PET/CT 8 29 64 13 114 78 (7186) 83 (7690) 69 (6178) 89 (8395) 82 (7489) 4.6 (0.88.5) 0.3 (0.71.2)
MRI 1 36 46 29 112
j
97 (94100) 61 (5270) 55 (4665) 98 (95101) 73 (6581) 2.5 (0.4 to 5.4) 0.0 (0.3 to 0.4)
a
False negative.
b
True positive.
c
True negative.
d
False positive.
e
Condence interval.
f
Positive predictive value.
g
Negative predictive value.
h
Positive likelihood ratio.
i
Negative likelihood ratio.
j
Two cases had severe metal artifacts and could not be interpreted on MRI.
Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295 289
PET/CT imaging
Patients were asked to fast for at least 6 h before the start of
the PET study. Serum glucose level was determined at the time
of intravenous injection of 370 MBq (10 mCi) of
18
F-FDG and all
the patients had glucose concentrations <200 mg/dL. PET/CT
images were acquired using a combined PET/CT scanner (Discov-
ery ST 16, GE Healthcare). To minimize FDG physiological uptake,
speech or swallowing was forbidden unless strictly necessary
from the intravenous injection of FDG to the completion of the
study. No muscle relaxants were used. Before PET acquisition,
helical CT images were obtained for anatomical localization/atten-
uation correction (AL/AC) from the head to the proximal thigh
according to a standardized protocol. The following settings were
used: transverse 10-mm collimation, 16-slice mode, 120 kVp, auto
mAs (range 10300), 0.5 s tube rotation, 17.5 mm/s table speed
and pitch 1.75. No intravenous contrast materials were adminis-
tered for the CT scan. CT data was resized from a 512 512 ma-
trix to a 128 128 matrix to match the PET data to allow for
image fusion and generation of CT transmission maps. Emission
data were acquired from the head to the proximal thigh at
50 min after intravenous injection of the tracer. Data were ac-
quired in two-dimensional mode (3 min per table position). The
study was performed with the arms positioned along the side of
the body and head holder was used. We did not perform a dedi-
cated regional study for the head and neck region in all partici-
pants following the whole-body acquisition. After CT-based AC,
PET images were reconstructed with an ordered subset expecta-
tion maximization iterative reconstruction algorithm (4 iterations
and 15 subsets). Slice thickness was 3.75 mm. All data were then
transferred to the processing workstation (Xeleris Workstation,
GE Healthcare). CT scans were displayed with a bone algorithm
and fused PET/CT images were evaluated in the axial, sagittal,
and coronal planes in the default window level. No threshold
was applied. Standardized uptake value (SUV) was dened as
the highest activity concentration per injected dose per body
weight (in kilograms) after correction for radioactive decay. Bone
marrow invasion was considered to be present if there was focal
FDG uptake within the marrow spaces contiguous with the pri-
mary tumor.
MRI imaging
All patients were examined using either a 1.5-T MRI (Intera,
Philips Medical Systems) or a 3.0-T (Magnetom Trio, Siemens
Table 3
Differences in sensitivity, specicity and accuracy between PET/CT and MRI for the
detection of bone marrow invasion in patients with squamous cell carcinoma of the
oral cavity.
Modality PET/CT p
FN
a
TP
b
TN
c
FP
d
MRI
FN
a
0 1 0 0 0.0391
e
TP
b
8 28 0 0 0.0015
f
TN
c
0 0 42 4 0.214
g
FP
d
0 0 20 9
a
False negative.
b
True positive.
c
True negative.
d
False positive.
e
Difference in sensitivity by McNemars test.
f
Difference in specicity by McNemars test.
g
Difference in area under the curve (AUC) by ROC curve analysis.
Table 4
Association of different clinical characteristics with sensitivity, specicity and positive likelihood ratios of PET/CT in 65 patients with squamous cell carcinoma of the oral cavity
and positive MRI for marrow invasion.
Characteristic n FN
a
TP
b
TN
c
FP
d
Sensitivity (95% CI
e
) p Specicity (95% CI
e
) p LR+
f
(95% CI
e
)
Anatomical subsite
g
Buccal 20 4 3 8 5 43 (2165) 0.0014
*
62 (4083) 0.8259 1.1 (3.5 to 5.7)
Alveolar ridge 33 3 22 5 3 88 (7799) 63 (4679) 2.3 (2.8 to 7.5)
Differentiation
Well/moderate 57 7 26 16 8 79 (6889) 0.7572 67 (5479) 0.7375 2.4 (1.6 to 6.3)
Poor 8 1 2 4 1 67 (3499) 80 (52108) 3.3 (9.1 to 15.8)
Metal-related artifacts
No 28 3 11 11 3 79 (6394) 0.9129 79 (6394) 0.1739 3.7 (3.3 to 10.6)
Yes 37 5 17 9 6 77 (6491) 60 (4476) 1.9 (2.5 to 6.4)
Dental status
Dentate 28 3 10 13 2 77 (6193) 0.8379 87 (7499) 0.0043
*
5.8 (2.9 to 14.4)
Edentulous 37 5 18 7 7 78 (6592) 50 (3466) 1.6 (2.4 to 5.6)
Primary tumor size (cm)
64.8 (ROC) 42 3 18 14 7 86 (7596) 0.3700 67 (5281) 0.6970 2.6 (2.2 to 7.4)
>4.8 23 5 10 6 2 67 (4786) 75 (5793) 2.7 (3.9 to 9.3)
SUV of the primary tumor
613.43 30 2 12 12 4 86 (7398) 0.3284 75 (6090) 0.3934 3.4 (3.1 to 9.9)
>13.43 35 6 16 8 5 73 (5887) 62 (4578) 1.9 (2.6 to 6.4)
Patient groups
g
Dentate alveolar ridge 8 1 4 3 0 80 (52108) 0.0025
*
100 0.1165 #
i
Dentate buccal 10 1 3 4 2 75 (48102) 0.0027
*
67 (3796) 1.0000 2.3 (6.9 to 11.4)
Edentulous alveolar ridge 25 2 18 2 3 90 (78102) <0.0001
*
40 (2159) 0.5910 1.5 (3.3 to 6.3)
Edentulous buccal
h
10 3 0 4 3 0 57 (2688) 0.0 (0.00.0)
a
False negative.
b
True positive.
c
True negative.
d
False positive.
e
Condence interval.
f
Positive likelihood ratio.
g
Only the two major subsites (buccal and alveolar ridge) were analyzed for this parameter.
h
Reference group.
i
False-positive rate equals zero, consequently positive likelihood ratio (LR+) is innity.
*
Statistically signicant difference.
290 Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295
Healthcare, Erlangen, Germany) MRI scanner. The MRI examina-
tions were performed using a head-and-neck synergic coil to cover
the entire neck fromthe skull base to the thoracic inlet. T2- and T1-
weighted fast/turbo spinecho sequences were applied in the axial
plane. Post gadolinium contrast enhanced T1-weighted fast/turbo
spinecho sequences with fat saturation were applied in the axial,
coronal, and sagittal planes at 4-mm slice thickness. All data were
archived in DICOM format and transferred to a stand-alone work-
station for processing. All of the imaging analysis was performed
on a picture archiving and communication system (PACS) worksta-
tion (Centricity 1.0; GE Healthcare, Milwaukee, WI, USA). Tumor
invasion into the bone marrow was diagnosed by replacement of
the marrow fat of the involved mandible or maxilla by contiguous
tumors with abnormal T1 hypointensity, T2 hyperintensity, and
denite contrast enhancement. Bone erosion was considered to
be present if there was any irregular bone thinning while bone
destruction was diagnosed in the presence of complete cortical
bone loss. MR image distortions or artifacts close to the maxilla
or mandible were carefully recorded.
Image interpretation
PET/CT images were reviewed by one nuclear physician (6 years
experience in general nuclear medicine, 2 years in PET/CT) and one
head-and-neck radiologist (20 years experience), and a consensus
was reached via joint reevaluation of the images. All MRI data were
read by an independent head-and-neck radiologist (7 years experi-
ence), who was blinded to PET/CT ndings. The readers were aware
of tumor origin and side. The images were evaluated qualitatively
for the presence of bone marrow invasion on a 5-point score, in
which a score of 0 indicated that bone marrow invasion was de-
nitely absent; a score of 1, bone marrow invasion was probably ab-
sent; a score of 2, ambiguous cases characterized by cortical bone
erosion in the absence of overt bone destruction; a score of 3, bone
marrow invasion was probably present; and a score of 4, bone
marrow invasion was denitely present. A score of 2 or less was
considered negative. SUV was not considered in the image
interpretation.
Statistical analysis
Receiver operating characteristic (ROC) curve analysis was per-
formed to assess discriminative power of PET/CT and MRI for bone
marrow invasion. Histopathology was taken as the reference stan-
dard; sensitivity, specicity, predictive values and likelihood ratios
were calculated for expressing test performance. Categorical data
and paired readings were analyzed using the Chi-squared (v
2
) test
and the McNemars test, respectively. We determined the optimal
cutoff values for tumor size and maximum SUV by ROC analysis
based on the presence of bone marrow invasion. SUVmax was
compared in two sub-groups using Students t-test for independent
samples. All statistical analyses were two-sided and the signi-
cance level was xed at 0.05.
Table 5
False-negative and false-positive results of PET/CT for the detection of bone marrow invasion in patients with squamous cell carcinoma of the oral cavity.
No. Anatomical
subsite
Dental
status
Metal-
related
artifacts
Differentiation cT
a
pT
b
Tumor
size
(cm)
SUV
c
primary
tumor
Bone
management
Marrow
invasion
PET/CT
score
PET/CT
result
MRI
score
MRI
result
1 AR
d
Dentate + MD
f
T4 T4 3.5 8.1 SM
i
+ 2 FN
l
4 TP
n
2 Buccal Edentulous + MD
f
T4 T4 5 33.4 SM
i
+ MX
j
+ 2 FN
l
4 TP
n
3 AR
d
Edentulous + MD
f
T4 T4 3.2 16.9 SM
i
+ 0 FN
l
4 TP
n
4 Buccal Edentulous + WD
g
T4 T4 9 10.7 SM
i
+ MX
j
+ 2 FN
l
4 TP
n
5 Buccal Edentulous + PD
h
T4 T4 6 16.8 SM
i
+ MX
j
+ 2 FN
l
4 TP
n
6 Buccal Dentate MD
f
T4 T4 5.2 13.5 SM
i
+ MX
j
+ 2 FN
l
4 TP
n
7 AR
d
Edentulous MD
f
T4 T4 2.8 25.3 SM
i
+ 0 FN
l
4 TP
n
8 RMT
e
Dentate MD
f
T4 T4 5.3 20.9 SM
i
+ 0 FN
l
4 TP
n
9 RMT
e
Edentulous WD
g
T4 T4 3.5 14.3 SM
i
+ MX
j
4 FP
m
4 FP
m
10 Buccal Edentulous + MD
f
T4 T4 4.8 12.6 MM
k
+ MX
j
4 FP
m
4 FP
m
11 AR
d
Edentulous + MD
f
T4 T3 5 12.6 SM
i
4 FP
m
4 FP
m
12 Buccal Edentulous + MD
f
T4 T4 4.2 20.2 SM
i
3 FP
m
4 FP
m
13 Buccal Edentulous MD
f
T4 T4 6.5 22 SM
i
+ MX
j
3 FP
m
4 FP
m
14 Buccal Dentate + MD
f
T4 T4 4.5 13.2 MM
k
+ MX
j
4 FP
m
4 FP
m
15 Buccal Dentate + WD
g
T4 T3 4.5 11.3 MM
k
+ MX
j
3 FP
m
4 FP
m
16 AR
d
Edentulous WD
g
T4 T3 3.8 19.8 SM
i
+ MX
j
3 FP
m
4 FP
m
17 AR
d
Edentulous + PD
h
T4 T2 2.5 14.6 MM
k
+ MX
j
4 FP
m
4 FP
m
18 Buccal Dentate + WD
g
T2 T2 3.5 23.4 MM
k
+ MX
j
4 FP
m
2 TN
o
19 AR
d
Edentulous + WD
g
T2 T2 2.3 10.3 MM
k
3 FP
m
2 TN
o
20 AR
d
Edentulous + PD
h
T3 T3 5 4.4 SM
i
+ MX
j
4 FP
m
2 TN
o
21 Buccal Edentulous MD
f
T2 T2 3.5 22.3 MM
k
+ MX
j
3 FP
m
1 TN
o
a
Clinical tumor status.
b
Pathological tumor status.
c
Standardized uptake value.
d
Alveolar ridge.
e
Retromolar trigone.
f
Moderately differentiated.
g
Well differentiated.
h
Poorly differentiated.
i
Segmental mandibulectomy.
j
Maxillectomy.
k
Marginal mandibulectomy.
l
False negative.
m
False positive.
n
True positive.
o
True negative.
Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295 291
Results
General characteristics
One hundred fourteen patients with squamous cell carcinoma
of the oral cavity were enrolled (Table 1). The median time interval
between diagnostic studies (PET/CT and MRI) and surgery was
2 days (range: 121 days for PET/CT; 156 days for MRI). The two
studies (PET/CT and MRI) were done within 4 weeks of each other,
except for one patient, who underwent MRI 54 days before PET/CT.
Histopathological examination revealed the presence of marrow
invasion in 37 patients (32.5%). More than 85% of the patients
had the habits of cigarette smoking and betel quid chewing. The
predominant tumor origins were buccal mucosa (41.2%) and alve-
olar ridge (34.2%).
Sixty-one patients had metal-related artifacts; in two of them,
the MRI was severely distorted and uninterpretable. These two pa-
tients were excluded from any subsequent comparative analyses.
The presence of metal artifacts did not affect the performance of
PET/CT. However, we encountered a single false negative result
due to misregistration between PET and CT. The FDG activity
seemed to be displaced by a few millimeters fromthe site of CT-de-
tected cortical erosion (scored 2 by consensus).
Diagnostic performance
MRI showed the highest sensitivity and negative predictive val-
ues (97% and 98%, respectively) with only one false negative result
(Table 2). However, low specicity and positive predictive values
were encountered (61% and 55%, respectively). Twenty-nine false-
positive results were seen. Sensitivity and specicity of PET/CT
were 78% and 83% respectively with 8 false negative and 13 false-
positive results. Combined PET/CT was signicantly more specic
(83% vs. 61%, p = 0.0015) and less sensitive than MRI (78% vs. 97%,
p = 0.0391). The overall accuracy was comparable (Table 3).
Clinical factors affecting PET/CT performance
Tumor origin and dentate status were found to affect the diag-
nostic performance of PET/CT. Bone marrow invasion was signi-
cantly higher in edentulous patients than in dentate patients (23/
50 vs. 14/64, p = 0.009). In dentate patients, PET/CT had higher
Figure 1 Imaging ndings of a 56-year-old man with a diagnosis of squamous cell carcinoma of the left buccal mucosa, (A) coronal fused PET/CT image of the tumor mass
without FDG uptake within the marrow cavity of the mandible. The corresponding non-contrast-enhanced CT image (B) demonstrated the presence of cortical bone erosion
only. Post gadolinium contrast enhancement coronal T2 (C) and T1 (D) MR weighted images showed a left buccal-gum cancer, with hyperintensity and enhancement in the
bone marrow of left mandible, suggesting bone marrow invasion. Pathological results were positive for marrow invasion.
292 Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295
specicity (94% vs. 63%, p = 0.0001) and positive likelihood ratio
([LR+], 13.1 vs. 2.1). A total of 13 false-positive results were
encountered, 10 of them were seen in edentulous patients. Inter-
estingly, all the false-positive results were in patients who had
the habit of betel quid chewing.
Alveolar ridge and buccal mucosa represented the two major
tumor origins in our study (n = 39 and 47, respectively). Tumors
originating in the alveolar ridge were signicantly associated with
more bone marrow invasion (25/39 vs. 7/47, p < 0.0001). Consider-
ing only these two subsites, PET/CT offered signicant advantages
in terms of sensitivity (88% vs. 43%, p < 0.0001) and positive predic-
tive value (81% vs. 30%, p < 0.0001) in alveolar ridge tumors com-
pared with buccal tumors.
There was a trend toward higher sensitivity, specicity, and LR+
when the size of the tumors was less than 4.8 cm or the SUV values
less than 13.43 mg/mL.
MRI was positive in 65 patients; 29 of them were falsely posi-
tive. Given this high false positive rate, we tried to identify a sub-
group of patients with MRI-positive ndings in whom PET/CT may
be useful (Table 4). Among these 65 patients, MRI gave false-posi-
tive results in 53.6% of dentate patients (15/28). PET/CT success-
fully excluded the presence of bone marrow invasion in 13 of
these 15 cases. In alveolar ridge tumors (n = 33), PET/CT also ex-
cluded disease in 5 out of 8 falsely positive MRI results. False-neg-
ative and false-positive results of PET/CT for the detection of bone
marrow invasion in this study are shown in Table 5.
Discussion
Assessment of facial bones invasion by OSCC is important for
head and neck surgical oncologists before treatment planning. In
the past, we largely relied on the ndings from physical examina-
tion plus conventional images, such as panorex X-ray, CT and/or
MRI with unsatisfying results, especially when patients had a cer-
tain degree of dental problems. Studies from other groups have
shown that both PET/CT and SPECT/CT may be clinically useful,
with varying degrees of sensitivity (58.3100%, 92%, 41.7100%,
39.1100%) and specicity (85100%, 86%, 57.1100%, 4097.1%)
for PET/CT, SPECT/CT, CT, and MRI, respectively.
1215
In this study,
we found a sensitivity and specicity of 78% and 83% for PET/CT,
and 97% and 61% for MRI, respectively. Our data suggest that
PET/CT may complement the role of MRI for diagnosing bone mar-
row invasion in patients with oral cavity cancer. A negative MRI
Figure 2 Imaging ndings of a 41-year-old man with a diagnosis of squamous cell carcinoma of the right buccal mucosa, (A) transaxial fused PET/CT image of the tumor mass
that shows intense FDG uptake (SUVmax = 22.3) and it violates the bone boundary of the maxilla. The corresponding coronal non-contrast-enhanced CT image (B)
demonstrated the presence of cortical discontinuity, and also evidence of some periodontal disease. The lesion scored 4 on PET/CT by consensus. Post gadolinium contrast
enhancement axial T2 (C) and T1 (D) MR weighted images showed right upper gum cancer without abnormal signal intensity at right maxilla, suggestive of no bone marrow
invasion. Pathological result was negative for marrow invasion.
Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295 293
scan could condently exclude the presence of marrow invasion in
patients with OCSCC. However, positive results obtained with this
modality cannot always be considered true positive and PET/CT
scan may help to make the diagnosis. We encountered a single
false negative MRI result. Our ndings concerning the high nega-
tive predictive value of MRI were well in line with the results of
previous studies.
611
In our experience, there are two possible reasons to explain the
higher false-positive results. First, Taiwan is an endemic area for
betel quid chewing, and oral cancers in association with trismus
with subsequent poor oral hygiene are commonly seen in clinical
practice.
16,17
Betel quid chewing was observed in 87% of patients
in this study. There were 28 false-positive results out of 99 patients
chewing betel quid compared to 1/15 patients not having this habit
(positive predictive value = 51% vs. 88%, p = 0.02). Second, all the
studied tumors were involving the alveolar ridge, which could eli-
cit a local inammatory response. It has been reported that MRI
may yield falsely positive results in inammatory odontogenic
disease.
18
We encountered 8 false-negative PET/CT ndings (Table 5); in 4
of them, the non-optimized CT intended for AC/AL was unable to
detect sites of minimal bone breakthrough. We assume that a more
optimized CT protocol for the head and neck region may add to the
diagnostic yield of PET/CT. The other 4 false-negative PET/CT
results were either due to low tracer uptake in the bone marrow
(patients # 1 and # 6), misregistration of the CT and PET images
(Patient # 5) or retraction of the edentulous alveolar ridge (Patient
# 2), which mislead the localization of FDG uptake (Fig. 1). PET/CT
showed signicantly higher false positive rate in edentulous com-
pared to dentate patients (37% vs. 6%, p = 0.0001). The reason for
that may be explained by: (a) Repeated episodes of periodontitis
are common in edentulous patients which may show avidity to
FDG (Fig. 2).
19
(b) The mean SUV of the primary tumor was signif-
icantly higher in edentulous compared to dentate patients (15.2 vs.
12.6, p = 0.036). High FDG uptake may produce a spillover effect,
leading to overestimation of the exact tumor extension (Fig. 3).
20
In this study, the sensitivity and positive predictive value of
PET/CT were signicantly lower for buccal compared to alveolar
ridge tumors; however, the negative predictive value, LR+ and
overall accuracy remained comparable. Of note, among all the
false-positive results encountered by PET/CT, the mean SUV within
buccal tumors was higher, though not signicantly, than that seen
in alveolar ridge tumors (17.8 vs. 12.3, p = 0.1).
Our study is not without important limitations. A head and neck
PET/CT study was not performed in all participants following the
whole-body acquisition. No contrast media were used routinely
for the CT portion of PET/CT. Moreover, the CT portion of PET/CT
was not optimized for diagnostic purpose. In addition, the inevita-
ble partial volume effect in PET/CT should be considered. Finally,
this study is a retrospective single-reader analysis, which reects
a single center experience. Strengths of our report include the large
sample size, the use of histopathological examination as the gold
standard for comparison, and the homogeneity of diagnosis and
treatment plans.
Figure 3 Imaging ndings of a 43-year-old man with a diagnosis of squamous cell carcinoma of the right buccal mucosa, (A) coronal fused PET/CT image of the tumor mass
that shows intense FDG uptake (SUVmax = 22) and it violates the bone boundary of the mandible. The corresponding coronal non-contrast-enhanced CT image (B)
demonstrated the presence of cortical erosion in the edentulous alveolar socket and possible breakthrough. Post gadolinium contrast enhancement coronal T2 (C) and T1 (D)
MR weighted images showed right buccal-gum cancer with mild bone erosion on the edentate alveolar socket. No abnormal signal intensity at right mandible, indicating
bone cortex invasion without bone marrow involvement. Pathological result was positive for both periosteal and cortical invasion but negative for marrow invasion.
294 Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295
Conclusion
PET/CT is more specic than MRI and can be used to comple-
ment the role of MRI. A negative MRI result can condently exclude
the presence of bone marrow invasion in patients with squamous
cell carcinomas of the oral cavity. In dentate patients with positive
MRI ndings, a negative PET/CT may be useful to rule out bone
marrow invasion in dentate patients. PET/CT had a signicantly
higher sensitivity and positive predictive value in alveolar ridge tu-
mors compared to buccal mucosa tumors.
Conict of Interest
None declared.
Acknowledgements
This work was supported in part by a Grant-in-Aid for FDG PET
Research in Oral Cancer from Chang Gung Memorial Hospital-Link-
ou (CMRPG370062).
References
1. Barttelbort SW, Bahn SL, Ariyan SA. Rim mandibulectomy for cancer of the oral
cavity. Am J Surg 1987;154(4):4238.
2. Ord RA, Sarmadi M, Papadimitrou J. A comparison of segmental and marginal
bony resection for oral squamous cell carcinoma involving the mandible. J Oral
Maxillofac Surg 1997;55(5):4707. discussion 78.
3. Politi M, Costa F, Robiony M, Rinaldo A, Ferlito A. Review of segmental and
marginal resection of the mandible in patients with oral cancer. Acta
Otolaryngol 2000;120(5):56979.
4. Wax MK, Bascom DA, Myers LL. Marginal mandibulectomy vs segmental
mandibulectomy: indications and controversies. Arch Otolaryngol Head Neck
Surg 2002;128(5):6003.
5. Ahmad A, Branstetter BF. CT versus MR: still a tough decision. Otolaryngol Clin
North Am 2008;41(1):122.
6. Rajesh A, Khan A, Kendall C, Hayter J, Cherryman G. Can magnetic resonance
imaging replace single photon computed tomography and computed
tomography in detecting bony invasion in patients with oral squamous cell
carcinoma? Br J Oral Maxillofac Surg 2008;46(1):114.
7. Tsue TT, McCulloch TM, Girod DA, Couper DJ, Weymuller Jr EA, Glenn MG.
Predictors of carcinomatous invasion of the mandible. Head Neck
1994;16(2):11626.
8. Van Cann EM, Koole R, Oyen WJ, de Rooy JW, de Wilde PC, Slootweg PJ, et al.
Assessment of mandibular invasion of squamous cell carcinoma by various
modes of imaging: constructing a diagnostic algorithm. Int J Oral Maxillofac Surg
2008;37(6):53541.
9. van den Brekel MW, Runne RW, Smeele LE, Tiwari RM, Snow GB, Castelijns JA.
Assessment of tumour invasion into the mandible: the value of different
imaging techniques. Eur Radiol 1998;8(9):15527.
10. Bolzoni A, Cappiello J, Piazza C, Peretti G, Maroldi R, Farina D, et al. Diagnostic
accuracy of magnetic resonance imaging in the assessment of mandibular
involvement in oral-oropharyngeal squamous cell carcinoma: a prospective
study. Arch Otolaryngol Head Neck Surg 2004;130(7):83743.
11. Vidiri A, Guerrisi A, Pellini R, Manciocco V, Covello R, Mattioni O, et al. Multi-
detector row computed tomography (MDCT) and magnetic resonance imaging
(MRI) in the evaluation of the mandibular invasion by squamous cell
carcinomas (SCC) of the oral cavity. Correlation with pathological data. J Exp
Clin Cancer Res 2010;29:73.
12. Babin E, Desmonts C, Hamon M, Benateau H, Hitier M. PET/CT for assessing
mandibular invasion by intraoral squamous cell carcinomas. Clin Otolaryngol
2008;33(1):4751.
13. Goerres GW, Schmid DT, Schuknecht B, Eyrich GK. Bone invasion in patients
with oral cavity cancer: comparison of conventional CT with PET/CT and SPECT/
CT. Radiology 2005;237(1):2817.
14. Gu DH, Yoon DY, Park CH, Chang SK, Lim KJ, Seo YL, et al. CT, MR, (18)F-FDG
PET/CT, and their combined use for the assessment of mandibular invasion
by squamous cell carcinomas of the oral cavity. Acta Radiol 2010;51(10):
11119.
15. Pentenero M, Cistaro A, Brusa M, Ferraris MM, Pezzuto C, Carnino R, et al.
Accuracy of 18F-FDG-PET/CT for staging of oral squamous cell carcinoma. Head
Neck 2008;30(11):148896.
16. Liao CT, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, et al. Analysis of risk
factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol
2008;15(3):91522.
17. Lin CY, Wang HM, Kang CJ, Lee LY, Huang SF, Fan KH, et al. Primary tumor site
as a predictor of treatment outcome for denitive radiotherapy of advanced-
stage oral cavity cancers. Int J Radiat Oncol Biol Phys 2010;78(4):10119.
18. Imaizumi A, Yoshino N, Yamada I, Nagumo K, Amagasa T, Omura K, et al. A
potential pitfall of MR imaging for assessing mandibular invasion of squamous
cell carcinoma in the oral cavity. Am J Neuroradiol 2006;27(1):11422.
19. Shimamoto H, Tatsumi M, Kakimoto N, Hamada S, Shimosegawa E, Murakami S,
et al. (18)F-FDG accumulation in the oral cavity is associated with periodontal
disease and apical periodontitis: an initial demonstration on PET/CT. Ann Nucl
Med 2008;22(7):58793.
20. Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J
Nucl Med 2007;48(6):93245.
Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295 295

You might also like