Single photon emission computed tomography (SPECT) and SPECT/low-dose computerized tomography did...

Single photon emission computed tomography (SPECT) andSPECT/low-dose computerized tomography did not increasesensitivity or specificity compared to planar bonescintigraphy for detection of bone metastases in advancedbreast cancerAte Haraldsen, Henrik Bluhme, Lisbeth Røhl, Erik Morre Pedersen, Anders Bonde Jensen, Eva Boysen Hansen,Hanne Nellemann, Finn Rasmussen and Anni Morsing

Nuclear medicine Department & PET Center, Department of Radiology, Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark

Summary

CorrespondenceAte Haraldsen, Nuclear medicine Department &

PET Center, Norrebrogade 44, 8000 Aarhus C,

Denmark

E-mail: [email protected]

Accepted for publicationReceived 25 February 2014;

accepted 15 August 2014

Key wordsbone metastases; bone scintigraphy; breast cancer;

magnetic resonance imaging; SPECT/CT

Purpose To evaluate and compare the diagnostic performance of whole-body planarbone scintigraphy (WBS), single photon emission computed tomography(SPECT), SPECT/low-dose computerized tomography (SPECT/ldCT) and SPECT/contrast enhanced diagnostic CT (SPECT/cdCT) in the staging of patients withadvanced breast cancer.Methods Seventy-eight patients with recurrence of biopsy-proven breast cancer andsuspicion of disseminated disease were investigated with WBS, SPECT, SPECT/ldCT, SPECT/cdCT and MRI performed on the same day in this prospective study.Images were separately analysed in a blinded fashion by radiologists and nuclearmedicine physicians regarding the presence of pathological findings. MRI servedas reference standard.Results According to reference standard, 38 of 73 patients had bone metastases.The sensitivity was 87%, 87%, 79%, and 84% and specificity 63%, 71%, 63%and 83% for WBS, SPECT, SPECT/ldCT and SPECT/cdCT. A significantly increasedspecificity of SPECT/cdCT compared to WBS and SPECT/ldCT was found, andother parameters did not differ significantly between modalities. Additional twopatients had bone metastases solely located outside the MRI scan field and sevenpatients had soft tissue metastases, but no skeletal changes on MRI.Conclusion WBS, SPECT and SPECT/ldCT were less sensitive than MRI and equallyspecific for the detection of bone metastases in patients with advanced breast can-cer. Based on our findings, we suggest that initial staging include WBS, MRI ofthe spine and CT for soft tissue evaluation. Further studies may clarify the poten-tial benefits of whole-body MRI and 18F-NaF PET/CT or 18F-FDG PET/CT.

Introduction

Breast cancer is the most common cancer in women with an

annual incidence rate in Denmark of 144/100�000 (The Dan-

ish Cancer Registry 2011). Each year, around 1250 Danish

women will die from advanced breast cancer (The Danish

Register of Causes of Death 2011). It is therefore important

that timely and individually tailored treatment is launched to

optimize prognosis and increase survival.

Morbidity and survival of breast cancer are highly dependent

on whether the disease is localized or has disseminated. Bone is

the most frequent site of distant metastases and cause significant

morbidity. However, treatment with specific osteoclast inhibit-

ing drugs reduces the number of skeletal-related events, reduce

pain and improve quality of life. On that basis, precise and accu-

rate evaluation of skeletal involvement is important in the initial

work-up for the treatment planning.(Solomayer et al., 2000;

Hamaoka et al., 2004; Lluch et al., 2014) .

However, due to lack of evidence based on data from ran-

domized prospective studies, clear recommendations of algo-

rithms and use of imaging modalities for staging are not

available.

Clin Physiol Funct Imaging (2014) doi: 10.1111/cpf.12191

1© 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd

Due to its ability to evaluate the entire skeleton at a relatively

low-cost conventional 2-dimensional whole-body scintigraphy

(WBS) has been widely used for the detection of bone metasta-

ses in breast cancer. However, WBS relies on the osteoblastic

response to bone destruction and may be positive in increased

bone turnover of any aetiology such as malignancy, osteoar-

thritis, fractures or infection (Gates, 1998; Solomayer et al.,

2000). Specificity is therefore low and a positive finding often

necessitates further evaluation with computerized tomography

(CT), magnetic resonance imaging (MRI) or biopsy.

The use of new hybrid imaging technology supplementing

SPECT (3D examination) with CT has gained popularity

hypothesizing increased specificity as areas of stimulated bone

turnover may be correlated with anatomical changes such as

sclerosis, osteophytes, arthritis-related changes. Furthermore,

studies on mixed populations have indicated that sensitivity of

3D SPECT is superior to 2D WBS (Gates, 1998; Solomayer

et al., 2000; Savelli et al., 2001). However, prospective studies

in patients with advanced breast cancer comparing WBS and

SPECT/CT to a gold standard technique have to our knowl-

edge not been published.

MRI is considered an accurate and reliable method for addi-

tional evaluation of bone changes judged as possibly malig-

nant on bone scan (Kosuda et al., 1996). Furthermore, MRI

characterizes bone metastases as primarily lytic, sclerotic or

mixed and additionally visualize lesions in the bone marrow

(Even-Sapir, 2005; Vassiliou et al., 2007). As histological veri-

fication of each positive finding on WBS or SPECT/CT was

impossible for ethical and practical reasons, we chose to use

MRI as relative gold standard in the present prospective study.

To evaluate the hypothesized incremental effect on sensitiv-

ity, specificity and diagnostic accuracy of SPECT and SPECT/

CT compared to conventional WBS, we designed a prospective

study including women with recurrence of histopathological

proven breast cancer suspected of disseminated disease. A sec-

ondary aim was to suggest an algorithm suitable for reliable

and adequate staging for metastatic disease based on the prev-

alence of metastatic changes in this population.

Material and methods

Patients

Seventy-eight women (mean age 61�7, range 29–89) with

recurrence of histopathological proven breast cancer referred

to the Department of Oncology at Aarhus University Hospital

between May 2008 and June 2011 were consecutively

included in this prospective study. The study was approved by

the regional ethical committee, and oral and written consent

was obtained. The following imaging studies were performed

in 1 day: WBS, SPECT, SPECT/ldCT, SPECT/cdCT and MRI.

Five patients were excluded from the study; three because of

incomplete imaging sets, one because of concurrent multiple

myeloma and one because of lesions classified as equivocal on

MRI.

Clinical informations about the 73 patients included are

listed in Table 1.

Image acquisition

Bone scintigraphy

WBS was performed 3 h after injection of 750 MBq 99mTc-

dicarboxypropane diphosphonate according to a clinical rou-

tine protocol (scan time 20 min, LEUHR or LEHR collimator,

1024 9 256 or 1024 9 512 matrix) on a dual-head camera

(Picker Axis or Philips Precedence 16-slice SPECT/CT scanner;

Table 1 Clinical informations about the 73 patients included.

n Fraction (%)

Patient age (years)<40 1 140–49 7 1050–59 17 2360–69 34 47≥70 14 19Total 73

Tumour characteristicsSize (mm)<10 6 811–20 26 3621–30 21 2931–50 10 14≥50 8 11Unknown 2 3

Nodes0 20 271–5 31 42>5 18 25Unknown 4 5

ERPositive 56 77Negative 16 22Unknown 1 1

HER2Positive 23 32Negative 42 58Unknown 8 11

Previous treatmentNo prev. treatment 10 14Operation 50 68ChemotherapyCEF 22 30CMF 4 5Taxotere 6 8E/C 6 8

Herceptin 6 8Irradiation 44 60Endocrine therapyTamoxifen 38 52AI 21 29

ER, Estrogene receptor; HER2, Human Epidermal Growth FactorReceptor 2; CEF, Cyclophosphamide, Epirubicin, Fluorouracil; CMF,Cyclophosphamide, Methotrexate, Fluorouracil; E/C, Epirubicin/Cyclo-phosphamide; AI, Aromatase Inhibitor.

© 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd

Comparison of WB, SPECT and SPECT/ldCT in patients with breast cancer, A. Haraldsen et al.2

Philips Healthcare, Eindhoven, Holland) followed by SPECT

on the Philips Precedence camera (LEHR collimator, 128

views, 20 s/view, 128 9 128 matrix, zoom 1�46). SPECT

was reconstructed on a Philips Extended Brilliance Workspace

NM (Philips Healthcare), using Auto SPECT Pro (ASTONISH

iterative reconstruction, 4 iterations, 8 subsets including scat-

ter and ldCT attenuation correction and no filtering) and knit-

ted into a total body SPECT.

CT

CT from the base of the skull to the upper femoral region was

performed on the Philips Precedence scanner in immediate

sequence with the SPECT; ldCT (120 kV, 60 mAs/slice,

600 mm FOV, 512 9 512 matrix, 5 mm/slice, pitch 0�875,collimation 8 9 3) and cdCT (120 kV, 200 mAs/slice,

300 mm FOV, 512 9 512 matrix, 2 mm/slice, pitch 0�938,collimation 16 9 1�5). cdCT was performed as two-phase

spiral CT with arterial phase of the thorax and upper abdomen

and portovenous phase of the abdomen and pelvis using bolus

tracking technique after intravenous injection of Iodixanol

270 mgl ml-1 (Visipaque, GE Health Care, Oslo, Norway)

adjusted to body weight (2 ml kg bw-1). Additional recon-

struction was made of the arterial phase, with enhanced win-

dowing for bone (centre 650 HU, width 2600 HU) and

zoom to encompass the spine.

MRI

MRI of the total spine, sternum and pelvic bones was performed

on a 3T Philips Achieva scanner. For the spine standard, short

tau inversion recovery (STIR, TE=80 ms, TR=3300 ms. Inplane

resolution 1�0 9 1�3 mm) and T1 turbo spin echo (TSE,

TE=8 ms, TR=400 ms. Inplane resolution 1�0 mm 9 1�2 mm)

were acquired for the total spine in the sagittal plane acquiring

15 slices (slice thickness=4 mm). For the pelvic bones, a coro-

nal STIR (TE=57 ms, TR=7200 ms (inplane resolution 1�19 1�7 mm) and an axial T1 TSE (TE=18 ms, TR=594 ms.

Inplane resolution 1�1 9 1�3 mm) were performed.

Image analysis

All image data were stored on a HERMES server (Hermes

Medical Solutions, Sweden) and systematically blinded, so that

no cross reference could be made between modalities. The

blinded data were then redistributed to the physician’s respec-

tive workstations for later analysis. Each scan was analysed by

two experienced consultants in nuclear medicine (WBS,

SPECT, SPECT/ldCT), or in radiology (MRI), and consensus

was obtained without access to clinical data or findings on the

other imaging modalities. SPECT/cdCT was analysed side-by-

side by two nuclear medicine consultants and one radiology

consultant, and consensus was obtained. Data were entered

into separate case report forms for each reading. Any focus of

tracer accumulation or pathological appearance was classified

according to a three-point scale: (i) malignant, (ii) equivocal

or (iii) benign according to the following criteria:

On WBS and SPECT, focal tracer uptake was categorized as

malignant if not located adjacent to joints or representing

well-known normal variants in the sternum (Syed et al., 2005;

Kakhki & Zakavi, 2006) .

On SPECT/ldCT and SPECT/cdCT, focal tracer uptake was

characterized as malignant if not located adjacent to joints or

if corresponding to osteolytic, osteosclerotic mixed changes in

bone structure. Lesions were characterized as benign if local-

ized adjacent to joints or corresponding to benign degenera-

tive changes on CT such as osteophytes, spondylophytes,

subcondral sclerosis and narrowing of joint space. Lesions that

could not be identified as malignant or benign according to

the chosen criteria were categorized as equivocal.

On MRI, findings were characterized as (i) malignant, (ii)

equivocal or (iii) benign based on signal intensities, position

and composition on STIR and T1-weighted images and in

cases of equivocal findings on the course seen in consecutive

scans. Example is presented in Figure 1. On CT, malignant

lesions were suggested by the presence of lytic and/or scle-

rotic changes or as disruption of cortical bone. Furthermore,

enlarged lymph nodes and visceral metastases were described

and registered.

(a) (b) (c)

Figure 1 Horizontal view through pelvis in one patient on (a) SPECT/ldCT, (b) cdCT and (c) T1-weighted MRI showing metastases on SPECT/ldCT and MRI.


Comparison of WB, SPECT and SPECT/ldCT in patients with breast cancer, A. Haraldsen et al. 3

MRI was used as reference standard. To improve our refer-

ence standard, radiologists evaluated consecutive MRI scans

for patients with equivocal findings.

All data were stored in a database for subsequent analyses.

Statistical analysis

Data were analysed on patient level and region based. Sensitiv-

ity, specificity, accuracy, and positive and negative predictive

values (PPV and NPV) were calculated and compared with the

MRI using Fisher’s exact test and between modalities with

McNemar’s test. Lesions characterized as equivocal were

encountered in the group of malignant lesions.

On patient level, the patients were categorized as malignant

if the patient had at least one malignant lesion, equivocal if

no malignant lesions and at least one equivocal lesion and last

benign if no malignant or equivocal findings were seen.

Results

Patient characteristics are summarized in Table 1.

Of the 73 included patients, 38 had bone metastases based

on the reference standard including MRI of the spine, sternum

and pelvic bones. Two additional patients had bone metastases

exclusively located outside the MRI scan field of view identi-

fied on WBS or SPECT and confirmed by subsequent diagnos-

tic CT or MRI during follow-up (Fig. 2).

Diagnostic contrast enhanced CT identified soft tissue

metastases in 40 patients of whom seven did not have

bone metastases in the spine, sternum or pelvic bone on

MRI. In total, 45 patients of 73 had bone and/or soft tissue

metastases.

On each modality, the patients were classified as having a

malignant, benign or equivocal scan based on the findings

within the MRI scan field of view (Table 2). The scan were

categorized as malignant if the patient had at least one malig-

nant lesion, equivocal if no malignant lesions and at least one

equivocal lesion were present and last benign if no malignant

or equivocal findings were seen.

Table 2 show a significant decrease in the number of equiv-

ocal scans when performing SPECT and SPECT/ldCT compared

to WBS. On MRI, we have no equivocal scans because consec-

utive MRI scans were evaluated to improve our reference stan-

dard and 1 patient was excluded from the study because of

persisting equivocal scan on MRI.

Patient-based values of sensitivity, specificity, PPV, NPV and

diagnostic accuracy are given in Table 3 according to the MRI

scan field of view. SPECT/cdCT showed significant higher

specificity compared to WBS and SPECT/ldCT based on McNe-

mar0s test with a P-value of 0�046. Furthermore, the overlap-

ping 95% confidence intervals between WBS, SPECT and

SPECT/ldCT demonstrate that no difference was found

between any of these modalities. In particular did SPECT not

increase sensitivity compared to WBS and SPECT/ldCT did not

increase specificity compared to neither WBS nor SPECT.

Figure 3 shows the distribution of patients with bone

metastases in the different skeletal regions limited to areas

covered by all modalities. The shaded areas represent the

number of patients with false positive (red) or false negative

findings (blue) compared to MRI. In none of the regions did

SPECT prove superior sensitivity or SPECT/ldCT superior

specificity than WBS when compared to MRI. Figure 2 also

shows that half of the patients included in the study had bone

(a) (b)

Figure 2 (a) Anterior view of WBS from a patient with a single cos-tal bone metastasis. (b) Posterior view of WBS form another patientwith a solitary bone metastasis in the scull.

Table 2 Number of patients classified as malignant, equivocal orwithout findings suspicious of bone metastases on WB, SPECT,SPECT/ldCT, SPECTcdCT and MRI according to the MRI scan field ofview.

Patients

N = 73 WBS SPECT SPECT/ldCT SPECT/cdCT MRI

Malignant 31 38 35 28 38Equivocal 15 5 8 10 0Benign/Normal 27 30 30 35 35

WBS, whole-body planar bone scintigraphy; SPECT, single-photonemission computed tomography; CT, computerized tomography;SPECT/ldCT, SPECT/low-dose computerized tomography; SPECT/cdCT, SPECT/contrast enhanced diagnostic CT.



metastases in the thoracic spine making this location the pre-

dominating skeletal metastatic site in this population (Fig. 4).

Discussion

The present study is one of the first prospective study systemati-

cally comparing conventional WBS, SPECT and new hybrid

technology SPECT/CT for evaluation of bone metastases regard-

less of findings in each modality in women with advanced

breast cancer. All imaging studies including MRI were per-

formed on the same day allowing for direct comparison.

We have evaluated the performance of WB, SPECT, SPECT/

ldCT and SPECT/cdCT separately and not the added value of

modalities.

The present study confirms the high prevalence of metastatic

spread to the bone in patients with advanced breast cancer pre-

viously shown in retrospective studies (Hamaoka et al., 2004;

Manders et al., 2006). In the present study, half of the included

patients had skeletal metastases primarily located to the spine

and pelvis emphasizing the need for high accuracy in evaluation

of these regions. However, two patients had findings highly

suspicious of malignancy exclusively in areas such as skull and

costae, which were not covered by MRI, demonstrating the

need for whole-body evaluation. From the higher sensitivity of

MRI for detecting bone metastases in the present study, a

rational approach would be to extend the MRI coverage to the

entire skeletal system. A recent metaanalysis found PET and MRI

to be superior to both CT and WBS for detecting metastatic dis-

ease in bone (Yang et al., 2011), and a single study indicates

that previous shortcomings of MRI with respect to costal metas-

tases may have been overcome (Chen et al., 2012)

The skeleton is the predominating metastatic site in breast

cancer (Hamaoka et al., 2004). However, in the present study,

seven out of 73 patients had metastases in soft tissue but not

in bone demonstrating that complete staging of these patients

should include evaluation of both skeletal and soft tissue. Fur-

thermore, we found that the NPVs of WBS and SPECT were

only 81% and 83%, respectively, demonstrating that a nega-

tive bone scintigraphy (WBS or SPECT) cannot rule out skele-

tal metastases in these patients. This is in accordance with data

from a recent meta-analysis comparing bone scintigraphy and

PET/CT (Rong et al., 2013).

In accordance with previous findings in patients with pros-

tate and breast cancer, we found that WBS had a sensitivity of

87% for detection of bone metastases compared to MRI

(Even-Sapir, 2005; Shie et al., 2008; Rong et al., 2013) .

WBS detects areas in the bone where an osteoblastic response

is evoked by increased bone turnover. Malignant skeletal

involvement in advanced breast cancer may be lytic, blastic or

mixed suggesting that full evaluation cannot be based on imag-

ing modalities relying on osteoblastic response only. However,

Table 3 According to MRI scan field of view following table showper patient-based sensitivity, specificity, positive predictive value, neg-ative predictive value, and diagnostic accuracy of WB, SPECT, SPECT/ldCT and SPECT/cdCT compared to MRI in diagnosing bone metasta-ses (value with a 95% confidence interval).

WBS SPECT

SPECT/

ldCT

SPECT/

cdCT

Sensitivity(%)

87 (72–96) 87 (72–96) 79 (63–90) 84 (69–94)

Specificity(%)

63 (45–79) 71 (54–85) 63 (45–79) 83 (66–93)*

PPV (%) 72 (57–84) 77 (61–88) 70 (54–83) 84 (69–94)NPV (%) 81 (62–94) 83 (65–94) 73 (54–88) 83 (66–93)Diag.accuracy(%)

75 (64–100) 79 (68–100) 71 (59–100) 84 (73–100)

*McNemar0s test shows significant difference between WB andSPECT/ldCT compared to SPECT/cdCT; P = 0.046.WBS, whole-body planar bone scintigraphy; SPECT, single-photonemission computed tomography; CT, computerized tomography;SPECT/ldCT, SPECT/low-dose computerized tomography; SPECT/cdCT, SPECT/contrast enhanced diagnostic CT; PPV, positive predictivevalues; NPV, negative predictive values.

Figure 3 Distribution of true positive (red),true negative (blue), false positive (shadedred) and false negative findings (shaded blue)for all 5 modalities, separated in 5 anatomicalregions according to the MRI scan field ofview.



we found a sensitivity of 87% of SPECT compared to MRI

within identical field of view. As MRI identifies both blastic and

lytic metastases this suggest that the majority of bone metastases

in these patients lead to an osteoblastic response. This is sup-

ported by data from a study by Hahn et al. showing that the

majority of bone metastases in breast cancer appear to be mixed

osteblastic/osteolytic (Hahn et al., 2011).

Because of its two-dimensional structure, visualization of

increased uptake on WBS may be limited by the superimposi-

tion of structures. Even-Sapir and others showed that the

cross-sectional acquisition planes in SPECT increased sensitivity

compared to WBS in patients with high-risk prostate cancer

(Even-Sapir, 2005).

No significant difference in sensitivity for detecting bone

metastases between attenuation corrected SPECT and WBS was

demonstrated in the present study.

With specificities of 63% and 71% of WBS and SPECT,

respectively, our data confirm the limitation of WBS and

SPECT in discriminating between benign and malignant patho-

logical processes in the cortex.

Fusing SPECT images with simultaneous obtained low-dose

CT (SPECT/ldCT) enable anatomical localization of focal

increased bone turnover thereby potentially improving the dif-

ferentiation of benign versus malignant findings. However, in

the present study, SPECT/ld CT did not increase specificity

demonstrating that improving the anatomical localization of

scintigraphic findings was insufficient to distinguish benign

from malignant bone changes in this population. Our findings

are in accordance with results from a prospective study

including 100 oncologic and non-oncologic patients where

SPECT/ldCT did not increase specificity compared to SPECT

alone (Franc et al., 2012), but contrary to studies on mixed

populations (Gates, 1998; Costelloe et al., 2009; Palmedo et al.,

2014). The discrepancy between our data and the other stud-

ies may be explained by significant differences in study

design. We systematically imaged all patients regardless of

findings on either modality and without first identifying non-

specific and inconclusive findings on SPECT.

As reference standard we used MRI performed on the same

day as the other modalities evaluated in contrast to clinical

follow-up, which is temporally separated from the modalities

to be evaluated. MRI may have both false positives and false

negatives but has been proven more accurate in diagnosing

bone metastases compared to bone scintigraphy and CT (Yang

et al., 2011).

Administering medical oncology treatment may effectively

influence bone metastases and their appearance on imaging

modalities. Development of metastases is a dynamic process

and bone metastases can develop within a short time, making

follow-up as reference standard difficult.

SPECT/ldCT was examined as consensus reading by two

nuclear medicine consultants in contradiction to SPECT/cdCT,

which was consensus reading between two nuclear medicine

consultants and one radiology consultant.

SPECT/cdCT showed significantly higher specificity com-

pared to WBS and SPECT/ldCT based on McNemar0s test witha P-value of 0�046. If consensus reading of SPECT/ldCT was

made in association of nuclear medicine consultant and radiol-

ogy consultant, specificity might potentially be higher. How-

ever we find no significant change in accuracy, NPV, PPV and

sensitivity between SPECT/ldCT and SPECT/cdCT indicating

that only minor additional information may be overlooked on

the ldCT when solely viewed by nuclear medicine consultants.

Furthermore, we would expect a difference between perfor-

mance of ldCT and cdCT in favour of the latter.

Nevertheless, we found that SPECT and SPECT/ldCT reduced

the number of reader defined inconclusive studies compared to

WBS. This is in line with results from previous retrospective and

prospective studies in mixed patient populations suggesting that

the improved focal visualization and anatomical localization in

SPECT and SPECT/ldCT leads to a greater level of observer confi-

dence (Romer et al., 2006; Franc et al., 2012) .

(a) (b)

Figure 4 Sagittal view of one patient with a bone metastasis in sternum visualized on T2- and T1-weighted MRI, but not visual on SPECT/ldCT.



In the present study, five different modalities were used for

the evaluation of metastases in advanced breast cancer, a dis-

ease entity and population with a high pretest probability of

having disseminated disease. No single modality proved suffi-

cient for complete staging. In the cervical spine lesions may

be overlooked or not visualized by WBS and SPECT, SPECT/

ldCT could not exclude non-metastatic lesions, the skull and

costae were not included in the MRI field of view. It is there-

fore necessary to include more than one imaging modality in

the initial staging of these patients if relying on the modalities

used in the present study. The perspective is shared by Costel-

lo et al. but in contrast to their recommendation of using WBS

as gatekeeper for further imaging evaluation (Costelloe et al.,

2009). Because of the high pretest probability of benign as

well as malignant pathological skeletal findings and a relatively

large number of patients having soft tissue metastases exclu-

sively, we suggest that initial staging should include WBS,

MRI of the spine and CT for soft tissue evaluation. Future

studies may prove the role of whole-body MRI or PET/CT in

such one-stop-shop evaluation.

Conclusion

WBS, SPECT and SPECT/ldCT were less sensitive than MRI and

equally specific for the detection of bone metastases in

patients with advanced breast cancer. Based on our findings,

we suggest that initial staging include WBS, MRI of the spine

and CT for soft tissue evaluation. Further studies may clarify

the potential benefit of whole-body MRI and 18F-FDG PET/

CT.

Conflict of interest

The authors declare that they have no conflict of interest.

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