Whole-body SPECT-CT for bone scintigraphy:
diagnostic value and effect on patient management in
oncological patients
H. Palmedo1, C. Marx2, A. Ebert1, B. Kreft1, Y. Ko4, A. Türler5, R. Vorreuther6, U.
Göhring7, HH. Schild2, T. Gerhardt8, U. Pöge8, S. Ezziddin3, H.-J. Biersack3, H.
Ahmadzadehfar3.
Institute of Radiology and Nuclear Medicine and PET-CT Center Johanniter
Hospital, Bonn1
Department of Radiology, University Hospital Bonn2
Department of Nuclear Medicine, University Hospital Bonn3
Department of Internal Medicine/Clinical Cancer Center, Johanniter Hospital
Bonn4
Department of Surgery, Johanniter Hospital Bonn5
Department of Urology, Waldkrankenhaus Hospital Bonn6
Department of Obstetrics and Gynecology, Johanniter Hospital Bonn7
Institute of Internal Medicine/Nephrology Bonn8
Corresponding Author:
Prof. Dr. Holger Palmedo
Institute of Radiology and Nuclear Medicine and PET-CT Center
Johanniter Hospital, Kaiserstraße 19-21, 53113 Bonn, Germany
Email address holger.palmedo@gmx.de
1
Abstract
This study was designed to assess the additional value of single-photon
emission computed tomography (SPECT)-computed tomography (CT) of the
body trunk to conventional nuclear imaging and its effect on patient management
in a large patient series.
Material and methods: In 353 patients, whole-body scintigraphy (WBS),
SPECT, and SPECT-CT were prospectively performed for staging and restaging.
SPECT-CT of the trunk was performed in all patients. In the group of 308
evaluable patients (211 breast cancers, 97 prostate cancers), clinical follow-up
was used as the gold standard. Bone metastases were confirmed and excluded
in 72 and 236 cases, respectively. A multistep analysis per lesion as well as per
patient was performed. Clinical relevance was expressed by means of downand up-staging rates on a per-patient basis. Results: In the total patient group,
sensitivities, specificities, and negative and positive predictive values on a perpatient basis for WBS were respectively 93%, 78%, 95%, 59%; for SPECT
respectively 94%, 71%, 97%, 53% and for SPECT-CT respectively 97%, 94%,
97%, 88%. In all subgroups, specificity and positive predictive value were
significantly (p<0.01) better with the use of SPECT-CT. Down-staging of
metastatic disease in the total, breast cancer, and prostate cancer groups using
SPECT-CT was possible in 32.1%, 33.8%, and 29.5% of patients, respectively.
Up-staging of previously negative patients by additional SPECT-CT was
observed in 2.1% (3 cases) of breast cancer patients. Further diagnostic imaging
procedures for unclear scintigraphic findings were necessary in only 2.5% of
2
patients. SPECT-CT improved diagnostic accuracy for defining the extent of
multifocal metastatic disease in 34.6% of these cases. Conclusions: SPECT-CT
significantly improves the specificity and positive predictive value of bone
scintigraphy in cancer patients. In breast cancer patients, we found a slight
increase in sensitivity. SPECT-CT has a significant effect on clinical patient
management because of correct down- and up-staging, better definition of the
extent of metastases, and reduction of further diagnostic procedures.
Keywords: SPECT-CT, bone scintigraphy, bone metastases, prostate cancer,
breast cancer
3
Introduction
After the successful introduction of the image fusion technique known as
positron emission tomography (PET)-computed tomography (CT), strong
improvement has also been made in the development of new conventional
nuclear cameras.
Hybrid
single-photon emission
computed tomography
(SPECT)-CT gamma cameras have been available now for some years (1) and
combine the classic whole-body/SPECT imaging and high-resolution CT imaging
in one single construction (2). Furthermore, new reconstruction algorithms for
SPECT have been developed to enhance resolution of nuclear bone imaging (3),
which has led to a new diagnostic imaging method. In oncological patients, bone
scintigraphy is widely used to exclude or confirm bone metastases. One
shortcoming of this technique is its limited specificity in many cases (4). Often,
degenerative changes result in false-positive scintigraphic findings that need
additional radiological imaging, mainly x-ray images. However, the correlation of
secondary x-ray or CT images with scintigraphic imaging remains unclear in
many cases because of a lack of exact anatomical localization.
Some studies have shown that the number of unclear lesions identified
using whole-body planar scintigraphy and SPECT can be significantly decreased
by SPECT-CT (5-10). These investigations are mainly restricted to lesion-based
results, however, without using clinical follow-up as a gold standard or looking at
the effect on patient management. This study was designed to assess the
additional value of SPECT-CT to conventional nuclear imaging and its effect on
patient management in a large patient series.
4
Material and Methods
Patients and study design
This was a prospective study in a clinical setting. The findings from whole-body
scintigraphy, SPECT, and fused SPECT-CT images were compared with results
of clinical follow-up every 3–6 months during one year after imaging, as a gold
standard. For follow-up, clinical examinations, medical reports, imaging results,
and tumor markers were used. The evaluation of images was performed by a
central consensus reading. The images were scored blindly and independently
by two nuclear medicine physicians and one radiologist. The only clinical
information was the tumor diagnosis. The interpreting physicians then had to
compare their results and to reach consensus. If no consensus was found the
concerned patients should be part of a special analysis. During the consensus
read, special case records were accomplished beginning with the interpretation
of whole body images, followed by pure SPECT images and at last SPECT-CT
images. SPECT and SPECT-CT imaging of the trunk was not only performed as
lesion-guided but in all patients. This means that also patients with normal whole
body imaging underwent SPECT and SPECT-CT. All patients were informed
about the study and had given written consent according to the Declaration of
Helsinki.
We included patients with histopathologically proven tumor disease.
Patients were admitted to bone scintigraphy for staging or restaging due to
elevated risk for osseous metastases (bone pain, elevated tumor marker,
5
suspicious lesion(s) by different imaging modality). Exclusion criteria were as
follows: patients not feasible for performance of bone scintigraphy referring to the
guidelines (e.g. due to pain etc.), pregnancy or an age of < 18 y.
Imaging
All data were acquired with a combined SPECT-CT in-line system (Hawkeye 4
Infinia, General Electric; Symbia T2, Siemens Medical Solutions). These camera
systems integrate a dual-head SPECT camera with a four-slice helical CT
scanner and allow the acquisition of co-registered CT and SPECT images in one
session. Furthermore, conventional whole-body imaging is possible with these
cameras.
Whole-body scintigraphy, SPECT, and SPECT-CT imaging was performed
2–4 hours after administration of an average of 700 MBq (range 643-712 MBq)
Tc-99m methylene diphosphonate (MDP) using a standard acquisition with a
low-energy collimator: whole-body imaging at 10 cm per minute and additional
static imaging with a total of 500 kCts. SPECT images were obtained with 25
seconds per step acquiring 64 projections with 180-degree rotation for each
camera head. A 128 x 128 matrix was used. SPECT data were reconstructed
using a special high-resolution algorithm developed for bone scintigraphy.
For CT imaging, no intravenous contrast agent was administered. A lowdose technique was used with the following parameters: 2.5–20 mAs; 120 kV;
6
slice thickness, 2.5 - 5 mm; pitch, 1.5. SPECT over the same region was
performed before acquisition of the CT images.
Generally, patients were examined in the supine position with arms
elevated if possible. SPECT-CT of the trunk (from cervical region to proximal
femora) was obtained using a special whole-body SPECT software option that
covered a total area of two SPECT fields. This results in an imaging time of 25
minutes.
Interpretation
Images were interpreted at workstations equipped with fusion software (Infinia,
General Electric; Syngo, Siemens) that provides whole-body imaging as well as
multiplanar reformatted SPECT and CT images. It enables display of SPECT,
CT, and fused SPECT-CT images in any percentage relation.
Analysis of images was performed as a multistep image interpretation (11).
During the first step, whole-body (and if performed, static) images were scored
blindly and independently by two nuclear medicine physicians and one
radiologist. For this purpose, a 5-point scale was used: a score of 0 indicated
that the lesion was normal; a score of 1 indicated that the lesion was probably
normal; a score of 2 indicated that the lesion was equivocal; a score of 3
indicated that the lesion was probably malignant; and a score of 4 indicated that
the lesion was malignant. The second step of data analysis consisted of the
same scoring of SPECT images in all three planes (coronal, sagittal,
7
transversal). The third step of interpretation was performed by evaluating the
fused SPECT-CT images, also in the three standard planes. A consensus
reading followed each patient evaluation. The 5-point interpretation was applied
to every lesion as well as to the patient.
A lesion was categorized as 0 or 1 if it did not follow the physiologic Tc-99m
MDP uptake patterns and was not thought to represent a tumor site. These
lesions showed uptake of low intensity or were located at the anatomic regions
or structures that can be associated with non-tumoral Tc-99m MDP uptake, such
as cartilage or joints. Lesions categorized as 3 or 4 had focal uptake of high
intensity or of suspicious accumulation pattern. All lesions were assigned to one
of the anatomic areas described below. If readers could not decide whether a
lesion was benign or malignant on the basis of the previous criteria, the lesion
was scored as 2.
Interpretation of whole-body, SPECT, and SPECT-CT images also included
the anatomic localization of Tc-99m MDP uptake sites. The anatomic assignment
of tumor lesions was made as detailed as possible; e.g., with specific
terminology such as “dorsal part of fourth thoracic vertebra.” For the general data
evaluation, a lesion was considered as true-positive if the score was 2–4 and if
follow-up was positive for bone metastases. A finding was considered as truenegative with score of 0–1 if follow-up examinations did not show any pathologic
result in the region of concern for at least 12 months. A lesion was considered as
false-positive if the score was 2–4 and if follow-up was negative. A finding was
considered a false-negative if the score was score 0–1 and if follow-up
8
examinations showed metastatic lesion(s). Additional analysis was performed
considering score 1 as the cut-off for malignancy (receiver operating
characteristic [ROC] analysis).
Clinically relevant, additional diagnostic information obtained by integrated
SPECT-CT images was considered if one or more of the following criteria were
met: the anatomic location of a suspicious lesion was not truly indicated by
whole-body and/or SPECT images but by fused SPECT-CT imaging; new tumor
sites diagnosed by fused imaging; false-positive lesions identified as truenegative by fused imaging. A finding was considered relevant for patient
management if it resulted in an significant down- or upstaging of the patient
(meaning conversion of a metastatic patient into a non-metastatic patient and
vice versa), in the prevention of further diagnostic imaging or if the extent of bone
metastases was changed.
Statistical analysis
The sensitivity, specificity, and negative and positive predictive values of wholebody scintigraphy, SPECT, and SPECT-CT were calculated on the basis of the
true-positive and true-negative findings as described in the same anatomic
region with a lesion-based and a patient-based analysis. The Bonferroni test was
used for comparison of sensitivity, specificity, and negative and positive
predictive values among the three imaging modalities with a confidence level of
95% (p<0.05 was considered significant).
9
Results
A total of 353 patients were included in the study. Of these patients, 45 could not
be included in the analysis because of missing follow-up data. Therefore, data
for 308 patients were available for study evaluation. Table 1 lists patient
characteristics.
Most patients (65.7%) were examined because of breast cancer. For one
third of the study population (32.8%), the cause of examination was prostate
cancer. During the follow-up period, bone metastases were confirmed in 72
patients (23.4%) and excluded in 236 (76.6%) patients.
Lesion analysis
A total of 839 lesions were examined. Most lesions were located in the spine and
pelvis. However, a significant number of lesions were found in other parts of the
skeleton (Table 2).
As Table 3 shows, scoring by whole-body scintigraphy led to benign,
indeterminate, or malignant classification in 28.6%, 18.7%, and 34.0% of the
lesions, respectively. By additional SPECT or SPECT-CT imaging, the
corresponding values were 33.0%, 20.4%, and 43.0% (SPECT) and 51.9%,
3.5%, and 36.4% (SPECT-CT) (in this evaluation, a score of 0 or 1 was
interpreted as benign, 2 as indeterminate, and 3 or 4 as malignant). In 67
patients, no lesion could be found at all. Overall, the total number of ‘scored
cases’ was 906 (839 lesions plus 67 patients without lesions).
10
For all three imaging modalities, there was no significant difference in
sensitivity if the number of lesions was considered. In addition, the better
specificity of SPECT-CT did not depend on the number of lesions.
Patient analysis
The absolute patient numbers as well as sensitivities, specificities, and negative
and positive predictive values of whole-body scintigraphy, SPECT, and SPECTCT are shown in Table 4 and Figure 1. By all three imaging modalities, 67
patients (93%) were classified as true-positive in a group of 72 patients with
metastatic disease; 172 true-negative patients (72.9%) were found among 236
metastasis-free patients by all three imaging techniques.
False-negative findings by all three modalities were identified in two
patients. Of these cases, one patient had breast cancer, one had prostate
cancer. The metastatic disease was detected by follow-up after 2 months by
additional imaging.
SPECT-CT diagnosed metastatic disease in the presence of negative
whole-body scintigraphy in 3 patients. In these three breast cancer patients,
metastatic disease was confirmed by magnetic resonance imaging (MRI) and
further follow-up.
False-positive findings on whole-body scintigraphy, SPECT, and SPECTCT were found in 50, 64, and 14 patients, respectively. In the 14 patients with
false-positive SPECT-CT, the result was mainly caused by benign alterations of
the rib (8 cases) and degeneration in the iliosacral joints (4), sternum (1), and
11
enchondroma (1). In comparison to whole-body scintigraphy, SPECT-CT could
convert false-positive patients into true negatives in 36 cases. Thus, 32.1% of
patients (36/112) scored positive by whole-body scintigraphy were staged down
by SPECT-CT to non-metastatic disease (down-staging rate, 32.1%). If a
positive score by whole-body scintigraphy with additional SPECT was
considered, the conversion rate of SPECT-CT was even higher at 39.7%
(50/126).
The patient numbers, sensitivities, specificities, and negative and positive
predictive values for breast cancer patients are shown in Table 5 and Figure 2.
Comparing whole-body scintigraphy and SPECT-CT, false-positive findings were
significantly less using SPECT-CT (in 23 patients). This corresponds to a downstaging rate of 33.8% (23/68 patients) in this patient group. Furthermore,
additional SPECT-CT imaging could convert three false-negatives into truepositive metastatic results, for an up-staging rate of 2.1% (3/143 patients).
In prostate cancer patients, the absolute patient numbers, sensitivities,
specificities, and negative and positive predictive values of all three imaging
modalities are shown in Table 6 and Figure 3. In comparison to whole-body
scintigraphy, SPECT-CT could correctly convert metastatic disease in nonmetastatic disease in 13 patients for a down-staging rate of 29.5% (13/44 cases).
No patient was up-staged.
12
ROC analysis
The change in sensitivity and specificity depending on the applied cut-off value is
shown in Figure 4. Looking at the total patient group, the area under the curve
was largest for SPECT-CT at 0.91 (whole-body scintigraphy, 0.89; SPECT,
0.89). The highest sensitivity as well as specificity was achieved by using a cutoff score of 2. Thus, all patients with the highest lesion score of 2 (indeterminate
lesion) or higher were considered as having metastatic disease. All patients with
a lesion score at a maximum of 1 or lower were considered as patients without
metastatic disease.
Clinical relevance and patient management
Additional diagnostic imaging for indeterminate findings was considered
necessary in 28.7%, 36.2%, and 2.5% of patients using whole-body scintigraphy,
SPECT, and SPECT-CT, respectively. Down-staging of metastatic disease in the
total group, in breast cancer, and prostate cancer patients using SPECT-CT was
possible in 32.1%, 33.8%, and 29.5%, respectively (table 7). Up-staging of
previously negative patients by additional SPECT-CT was observed in 2.1% of
breast cancer patients (see figure 5).
In 34.6% of patients with metastatic disease, the extent of metastatic
disease was more exactly characterized by means of SPECT-CT, which could
include or exclude regions scored as false-negative or false-positive by wholebody or SPECT imaging (see figure 6).
13
Discussion
We investigated the impact of additional SPECT-CT with low-dose application
and mainly whole-body technique in a large patient series. Planar whole-body
bone scintigraphy showed a sensitivity of 93% and specificity of 78% in the total
patient group. These values are within the range reported in previous studies,
demonstrating a sensitivity and specificity of 80%–95% and 62%–81%,
respectively (12, 13).
One limitation of planar whole-body bone scintigraphy is the rather low specificity
resulting from tracer accumulation in benign bone lesions, degenerative joint
alterations, and bone fractures (4). This low specificity leads frequently to
indeterminate results on bone scans that have to be reinvestigated by
complementary imaging like x-ray, CT, or MRI. Some clinicians have tried to
improve specificity by adding SPECT imaging (4); however, data showing an
advantage of this diagnostic algorithm are rare, supposedly because SPECT
also often cannot precisely localize a focal accumulation on whole-body
scintigraphy. In our study, specificity of whole-body scintigraphy could not be
improved by additional SPECT. In contrast, specificity was lower after
complementary SPECT because even more unclear lesions were detected.
The sensitivity of whole-body scintigraphy is considered to be sufficiently
high to exclude clinically relevant osseous metastases (14). No convincing
evidence supports the application of MRI or CT as a replacement for bone
scintigraphy in first-line imaging of osseous metastases (14). It is important to
mention that SPECT imaging has not been included in the vast majority of
14
studies comparing different imaging modalities. However, some studies have
shown that PET can provide small increments in diagnostic accuracy relative to
bone scintigraphy (15). This finding emphasizes the feasibility of promoting
nuclear techniques for image screening of bone metastases. In breast cancer
patients, PET with F-18 sodium-fluorine was more sensitive than whole-body
scintigraphy (15). In that study as well, however, no SPECT was performed. In
two studies with a similar design with prostate and lung cancer patients, NaF-18
PET and bone-SPECT were compared with whole-body scintigraphy (16). Crosssectional imaging PET and SPECT were found to be more sensitive than planar
whole-body scintigraphy for the detection of malignant bone lesions in these
patient groups (16, 17). In this situation as well, however, SPECT suffers from
the limitation of imprecise localization and the fact that only a small field of view
is examined, mainly reflecting the region with unclear lesions on whole body
scintigraphy.
In our study, we demonstrated that specificity can be improved significantly
by adding SPECT-CT to whole-body scintigraphy. On a per-patient analysis,
specificity was increased from 78% to 94% by the addition of SPECT-CT. For
112 patients showing unclear or suspicious findings on whole-body scintigraphy,
SPECT-CT could truly identify benign bone disease in 36 cases. Thus, about
one third (32.1%) of the patients suspected to have bone metastases or unclear
findings could be converted into metastasis-free patients. If whole-body
scintigraphy together with SPECT only was considered in comparison to SPECT-
15
CT, the conversion rate was even higher at 39.7% because SPECT generated
more unclear lesions than whole-body scintigraphy alone.
Recently published studies have investigated the effect of SPECT-CT
performed in the region of unclear lesions on whole-body scintigraphy (5-10).
These investigations demonstrated that the amount of indeterminate bone
lesions can be reduced from a rate between 48% and 72% (with whole-body
scintigraphy and/or SPECT) to a rate between 0% and 15% by additional
SPECT-CT. However, these evaluations were restricted to a per-lesion and not a
per-patient analysis. Indeed, data are limited for investigations of the impact of
SPECT-CT on patient-based diagnostic accuracy and patient management (9).
Our data show that sensitivity also can be improved by SPECT-CT.
However, this improvement was the case only in breast cancer patients, resulting
in an increase of sensitivity from 90.9% to 97.7% because three primarily
negative patients were converted into metastatic-positive patients.
One important aspect of our study was evaluation of the clinical relevance
of SPECT-CT. We estimate that our patient population in this clinical setting
represents rather the situation of a clinical everyday practice and not that of a
specially selected patient group. Furthermore, we performed a follow-up of
patients to meet a gold standard for diagnostic accuracy of SPECT-CT. The
number of patients who needed additional diagnostic imaging like x-ray, CT, or
MRI to characterize unclear findings was significantly reduced from 28.7% with
whole-body scintigraphy to 2.5% with SPECT-CT. One third of patients with
suspicious or unclear findings were truly down-staged to non-metastatic benign
16
disease. This effect was observed equally in the two tumor groups (breast and
prostate cancer) and is of high therapeutic relevance. Also, the up-staging rate of
2.1% in (whole-body) scintigraphically negative breast cancer patients is
clinically important. In 34% of patients with metastatic disease, the extent of
metastases was more precisely defined by SPECT-CT, indicating an
improvement in planning further patient treatment.
To achieve systematic improvement of specificity and sensitivity for bone
scintigraphy, it is not sufficient to perform a single-region SPECT-CT only in an
area with unclear or suspicious lesions detected on whole-body scintigraphy, as
studied in previous trials (5-9). A method that would offer advantages over this
strategy is whole-body SPECT-CT or SPECT-CT of the body trunk, as is done
with PET-CT. We have performed SPECT-CT from the cervical spine to the
proximal femora (what we call whole-body SPECT-CT) in all patients. Metastatic
lesions in the distal extremities without centrally located osseous metastases are
very rare (17), and we found no such cases in our study population.
Furthermore, we have shown that in comparison to conventional whole-body
scintigraphy, whole-body SPECT-CT has better specificity in both tumor groups
and also better sensitivity for breast cancer patients. This outcome leads to
clinically relevant down- and up-staging of tumor patient status as well as to
improved definition of extent of metastatic disease. Therefore, we speculate that
conventional whole-body scintigraphy could be replaced by whole-body SPECTCT (and additional planar images of the skull in larger patients) in the near
future, similar to the method of PET-CT. One limitation of this study, however, is
17
the fact that interpretation of whole-body SPECT-CT was done after
interpretation of conventional whole-body imaging. Therefore, a bias cannot be
excluded.
Radiation exposure is acceptably low if a low-dose CT technique is used.
Performing SPECT-CT of the trunk with a two field SPECT-CT and 2.5 mAs
results in an effective dose of 0.4 mSv. Thus, a significant improvement in
diagnostic accuracy and patient management can be achieved without
substantially increasing the radiation dose.
Conclusions
Adding SPECT-CT to whole-body imaging improves specificity significantly in
breast and prostate cancer. In breast cancer patients, sensitivity also can be
increased by SPECT-CT. In the clinical setting, the new technique of whole-body
SPECT-CT can result in better patient management because of clinically
relevant down- and up-staging of patients and a more precise identification of
metastatic extent. Whole-body SPECT-CT could replace conventional wholebody scintigraphy in the near future without substantially elevating the radiation
dose.
The authors declare that they have no conflict of interest
18
References
1.
Horger M, Eschmann SM, Pfannenberg C, et al. Evaluation of combined
transmission and emission tomography for classification of skeletal lesions. AJR
Am J Roentgenol. Sep 2004;183(3):655-661.
2.
Nomayr A, Romer W, Strobel D, Bautz W, Kuwert T. Anatomical accuracy of
hybrid SPECT/spiral CT in the lower spine. Nucl Med Commun. Jun
2006;27(6):521-528.
3.
Willowson K, Bailey DL, Baldock C. Quantitative SPECT reconstruction using
CT-derived corrections. Phys Med Biol. Jun 21 2008;53(12):3099-3112.
4.
Reinartz P, Schaffeldt J, Sabri O, et al. Benign versus malignant osseous lesions
in the lumbar vertebrae: differentiation by means of bone SPET. Eur J Nucl Med.
Jun 2000;27(6):721-726.
5.
Romer W, Nomayr A, Uder M, Bautz W, Kuwert T. SPECT-guided CT for
evaluating foci of increased bone metabolism classified as indeterminate on
SPECT in cancer patients. J Nucl Med. Jul 2006;47(7):1102-1106.
6.
Utsunomiya D, Shiraishi S, Imuta M, et al. Added value of SPECT/CT fusion in
assessing suspected bone metastasis: comparison with scintigraphy alone and
nonfused scintigraphy and CT. Radiology. Jan 2006;238(1):264-271.
7.
Strobel K, Burger C, Seifert B, Husarik DB, Soyka JD, Hany TF. Characterization
of focal bone lesions in the axial skeleton: performance of planar bone
scintigraphy compared with SPECT and SPECT fused with CT. AJR Am J
Roentgenol. May 2007;188(5):W467-474.
8.
Helyar V, Mohan HK, Barwick T, et al. The added value of multislice SPECT/CT
in patients with equivocal bony metastasis from carcinoma of the prostate. Eur J
Nucl Med Mol Imaging. Apr 2010;37(4):706-713.
9.
Zhao Z, Li L, Li F, Zhao L. Single photon emission computed tomography/spiral
computed tomography fusion imaging for the diagnosis of bone metastasis in
patients with known cancer. Skeletal Radiol. Feb 2010;39(2):147-153.
10.
Sharma P, Kumar R, Singh H, et al. Indeterminate lesions on planar bone
scintigraphy in lung cancer patients: SPECT, CT or SPECT-CT? Skeletal Radiol.
Jul 2012;41(7):843-50.
11.
Palmedo H, Bucerius J, Joe A, et al. Integrated PET/CT in differentiated thyroid
cancer: diagnostic accuracy and impact on patient management. J Nucl Med.
Apr 2006;47(4):616-624.
19
12.
Silvestri GA, Gould MK, Margolis ML, et al. Noninvasive staging of non-small cell
lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition).
Chest. Sep 2007;132(3 Suppl):178S-201S.
13.
Abuzallouf S, Dayes I, Lukka H. Baseline staging of newly diagnosed prostate
cancer: a summary of the literature. J Urol. Jun 2004;171(6 Pt 1):2122-2127.
14.
Houssami N, Costelloe CM. Imaging bone metastases in breast cancer:
evidence on comparative test accuracy. Ann Oncol. Apr 2012;23(4):834-843.
15.
Schirrmeister H, Guhlmann A, Kotzerke J, et al. Early detection and accurate
description of extent of metastatic bone disease in breast cancer with fluoride ion
and positron emission tomography. J Clin Oncol. Aug 1999;17(8):2381-2389.
16.
Schirrmeister H, Glatting G, Hetzel J, et al. Prospective evaluation of the clinical
value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly
diagnosed lung cancer. J Nucl Med. Dec 2001;42(12):1800-1804.
17.
Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I. The
detection of bone metastases in patients with high-risk prostate cancer: 99mTcMDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18Ffluoride PET, and 18F-fluoride PET/CT. J Nucl Med. Feb 2006;47(2):287-297.
18.
Bubendorf L, Schopfer A, Wagner U, et al. Metastatic patterns of prostate
cancer: an autopsy study of 1,589 patients. Hum Pathol. May 2000;31(5):578583.
20
Table 1: patient characteristics*
Number of patients
353
age (mean)
64.3 years
female
236 (66.8%)
male
117 (33.2%)
breast cancer
232 (65.7%)
prostate cancer
116 (32.8%)
others
5 (1.5%)
* including 45 patients with missing follow-up data
21
Table 2
anatomic region
number of lesions
percent
cervical spine
27
3.2
%
thoracic spine
218
25.9 %
lumbar spine
203
24.2 %
pelvis
211
25.2 %
ribs
68
8.1
%
sternum
17
2.0
%
shoulder
65
7,8
%
cranium
9
1.0
%
femora
21
2.6
%
total
839
100
%
* 67 patients were without any lesions
22
Table 3
Number of lesions/cases scored by whole-body scintigraphy, SPECT and
SPECT-CT
score
wbs*
SPECT
SPECT-CT
no lesion detectable**
157
18.7%
57
6.8%
69
8.2%
0 benign
68
8.1%
75
9.0%
335
39.9%
1 probably benign
172
20.5%
201
24.0%
101
12.0%
2 unclear
157
18.7%
171
20.4%
29
3.5%
3 probably malignant
127
15,2%
190
22.6%
65
7.7%
4 malignant
158
18.8%
145
17.2%
240
28.7%
total
839
100%
839
100%
839
100%
*
whole-body scintigraphy
**
the 67 patients without any lesions got the score „no lesion detectable“
23
Table 4: Sensitivity, specificity, and negative and positive predictive value of whole-body
scintigraphy, SPECT and SPECT-CT on the basis of a per patient analysis in the total
patient population.
sensitivity
wbs*
SPECT
SPECT-CT
specificity
NPV
PPV
93.0%
78.8%
95.4%
59.8%
67/72
186/236
186/196
67/112
93.0%
72.9%
94.5%
53.1%
67/72
172/236
172/182
67/126
97.2%
94.1%
97.4%
88.6%
70/72
222/236
223/229
70/79
* whole-body scintigraphy
24
Table 5: Sensitivity, specificity, and negative and positive predictive value of whole-body
scintigraphy, SPECT and SPECT-CT on the basis of a per patient analysis in breast
cancer patients.
wbs*
SPECT
SPECT-CT
sensitivity
specificity
NPV
PPV
90.9%
80.2%
93.7%
58.8%
40/44
134/167
134/143
40/68
90.9%
76.6%
93.4%
54.0%
40/44
128/167
128/137
40/74
97.7%
94.0%
97.1%
89.6%
43/44
157/167
158/163
43/48
* whole-body scintigraphy
25
Table 6: Sensitivity, specificity, and negative and positive predictive value of whole-body
scintigraphy, SPECT and SPECT-CT on the basis of a per patient analysis in prostate
cancer patients.
wbs*
SPECT
SPECT-CT
sensitivity
specificity
NPV
PPV
96.4%
75.3%
98.1%
61.4%
27/28
52/69
52/53
27/44
96.4%
63.7%
97.8%
51.9%
27/28
44/69
44/45
27/52
96.4%
94.2%
98.5%
87.1%
27/28
65/69
65/66
27/31
* whole-body scintigraphy
26
Table 7: Percentages of patients who were truly converted from metastatic or
suspicious finding to non-metastatic status (downstaging) or who were truly converted
from non-suspicious findings to metastatic disease (upstaging).
DownUpstaging to
Staging to
metastatic
nondisease
metastatic
total group
32.1%
1.5%
breast cancer
33.8%
2.1%
prostate cancer
29.5%
-
27
Legends:
Figure 1 - Diagnostic accuracies of whole body scintigraphy (WBS), SPECT and
SPECT-CT on the basis of a per patient analysis in the total patient population. * wholebody scintigraphy, ** significant difference p = 0,01
Figure 2 - Diagnostic accuracies of whole body scintigraphy (WBS), SPECT and
SPECT-CT on the basis of a per patient analysis in breast cancer patients. * whole-body
scintigraphy, ** significant difference p = 0,01
Figure 3 - Diagnostic accuracies of whole body scintigraphy (WBS), SPECT and
SPECT-CT on the basis of a per patient analysis in prostate cancer patients. * wholebody scintigraphy, ** significant difference p = 0,01
Figure 4 - ROC-Analysis for whole body scintigraphy (WBS), Spect and Spect-CT
referring to different cut-off points for the differentiation of metastatic and non-metastatic
patients in the total patient group.
28
Figure 5:
Bone scintigraphy of a 68 years old female patient with newly diagnosed breast cancer
who complained about moderate back pain. Whole body planar scintigraphy in ventral
(A) and dorsal (B) projection did not reveal any suspicious bone lesion. Only
hyperostosis frontalis was described which is an unspecific finding. Three years ago, the
patient has had an accident with a proximal femoral fracture on the left side. SPECT of
the body stem (maximal intensity projections = MIP) also did not demonstrate metastatic
bone disease (C). Only SPECT-CT (D) and CT (E) together could diagnose
disseminated bone metastases throughout the pelvis and the vertebral column showing
multiple small osteosklerotic lesions on CT-images (E) and, retrospectively, elevated
bone Up-take in some of these CT defined lesions (D). Disseminated bone metastases
were confirmed by MRI-imaging and further clinical follow up.
Figure 6:
Whole body SPECT (MIP images) of a 61 years old patient with prostate cancer
showing highly suspicious findings in the 4. thoracic vertebra, in the 1. lumbar vertebra
and the 5. lumbar vertebra (A, see arrows). SPECT and SPECT-CT could confirm
metastatic disease in the 4. thoracic vertebra (not shown), in the 1. lumbar vertebra (B,
C). Note that metastatic disease in this vertebra can be precisely differentiated from the
more ventrally located degenerative changes. This was also the case in the 4. thoracic
vertebra. The lesions in the 5. vertebra could be identified as degenerative changes of
the smaller intervertebral articulations(D, E). This demonstrates that extent of metastatic
disease can be determined by SPECT-CT more exact than by planar whole body
scintigraphy.
29