Rationale and Objectives
The aim of this review was to evaluate the diagnostic properties of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (CT) and bone scintigraphy in the detection of osseous metastases in patients with lung cancer.
Materials and Methods
MEDLINE was searched for relevant original articles published between January 1995 and August 2010. Inclusion criteria were as follows: FDG-PET or PET/CT and bone scintigraphy was carried out to detect bone metastases in patients with lung cancer, sufficient data were presented to construct a 2 × 2 contingency table, and histopathologic analysis and/or close clinical and imaging follow-up and/or radiographic confirmation by multiple imaging modalities was used as the reference standard. Two reviewers independently extracted data related to research design, sample size, imaging techniques, technical characteristics, reference standards, methods of imaging interpretation, and totals of true-positives, false-positives, true-negatives, and false-negatives. Stata was used to obtain per patient and per lesion pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios, and areas under summary receiver-operating characteristic curves (AUCs) were calculated.
Results
The pooled patient-based sensitivity of FDG-PET or PET/CT was 0.93 (95% confidence interval [CI], 0.88–0.96), specificity was 0.95 (95% CI, 0.91–0.98), and the AUC was 0.94. The pooled sensitivity of bone scans was 0.87 (95% CI, 0.79–0.93), specificity was 0.82 (95% CI, 0.62–0.92), and the AUC was 0.91. The pooled lesion-based sensitivity of FDG-PET or PET/CT was 0.93 (95% CI, 0.84–0.97), specificity was 0.91 (95% CI, 0.80–0.96), and the AUC was 0.97. The pooled sensitivity of bone scans was 0.92 (95% CI, 0.87–0.95), specificity was 0.57 (95% CI, 0.09–0.95), and the AUC was 0.92.
Conclusions
Although FDG-PET or PET/CT has higher sensitivity and specificity than bone scintigraphy, further research with a less biased design is needed to determine the most efficacious imaging modality for the detection of metastatic lung cancer.
Lung cancer is the most commonly diagnosed form of cancer as well as the leading cause of cancer death in men. Among women, lung cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death . A typical staging system includes the assessment of primary tumor characteristics, detection of lymph node metastasis, and detection of distant metastases to determine the treatment regimen for lung cancer. Historically, 30% to 40% of patients with advanced lung cancer have developed bone metastasis . Curative surgical resection is impossible in these late-stage patients. Alternatively, chemoradiotherapy, chemotherapy, targeted therapy, or best supportive care is considered advisable . Furthermore, with the development of newer, more sensitive screening and imaging technologies, the proportion of late-stage patients is expected to increase following initial implementation.
Osseous metastases in lung cancer are typically detectable via bone scintigraphy (BS), because of its high sensitivity and ability to survey the entire skeleton quickly at a relatively low cost. The uptake of skeletal-seeking radiotracers depicts osteoblastic activity and regional blood flow to bone. However, the specificity of BS is lowered by benign processes such as osteoarthritis, fractures, and inflammation. Suspicious abnormalities identified on BS generally require further investigation using x-ray, computed tomography (CT), magnetic resonance imaging, or biopsy for confirmation.
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Materials and methods
Literature Search
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Selection of Studies
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Data Extraction
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Table 1
Criteria Used to Assess the Methodologic Quality of the Studies
Criteria of Validity Positive Score Internal validity 1. Valid reference test Additional radiography, CT, MRI, biopsy, or follow-up 2. Blind measurement of BS, FDG-PET, or PET/CT without knowledge of reference test results 3. Blind measurement of reference test without knowledge of results of BS, FDG-PET, or PET/CT 4. Avoidance of verification bias Assessment by reference test independent of results of FDG-PET or PET/CT 5. BS, FDG-PET, or PET/CT interpreted independently of all clinical information Mentioned in publication 6. Prospective study Mentioned in publication External validity 1. Spectrum of disease Primary stage of disease 2. Demographic information Age and sex information given 3. Inclusion criteria Mentioned in publication 4. Exclusion criteria Mentioned in publication 5. Avoidance of selection bias Consecutive series of patients 6. Standard execution of BS, FDG-PET, or PET/CT Type of camera, dose of FDG, time interval, reconstruction
BS, bone scintigraphy; CT, computed tomography; FDG, 18 F-fluorodeoxyglucse; MRI, magnetic resonance imaging; PET, positron emission tomography.
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Statistical Analysis
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Results
Literature Search
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![Figure 1, Selection of studies. ∗ The inclusion criteria were as follows: (1) studies were reported in the English language; (2) they evaluated patients with lung cancer of all ages in any stage of disease, regardless of treatment status; (3) bone metastasis findings were confirmed with computed tomography, magnetic resonance imaging, or bone biopsy with clinical follow-up > 6 months; and (4) the two imaging modalities ( 18 F-fluorodeoxyglucose [FDG] positron emission tomography and bone scintigraphy [BS]) were performed within 3 months of each other. The exclusion criteria were as follows: (1) only FDG positron emission tomography or bone scanning was performed; (2) the total numbers of true-positives, false-positives, true-negatives, and false-negatives were not provided; and (3) no data from subanalyses were provided.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/Metaanalysis/0_1s20S1076633211005058.jpg)
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Table 2
Characteristics of Studies Evaluating FDG-PET and BS for the Detection of Osseous Metastasis From Lung Cancer
Study Year Sample Size Study Type Data Type PET Technique BS Technique Statistical Test Notes Bury et al 1998 110 Retrospective cohort Patient based 200–250 MBq FDG, uptake 60–90 min 20 mCi 99m Tc diphosphonate, 4-h delay — Hsia et al 2002 48 Retrospective cohort Lesion based 10 mCi (370 MBq) FDG, uptake 30–45 min 925 MBq 99m Tc MDP, 2-h to 3-h delay — Gayed et al 2003 82 Retrospective cohort Patient and lesion based 555 MBq FDG, uptake 60 min 1036–1110 MBq 99m Tc MDP, 90-min to 120-min delay Weighted average Cheran et al 2004 257 Retrospective cohort Patient-based 5.365 MBq/kg, maximum 20 mCi, uptake 30 min 430 μCi/kg (maximum 30.0 mCi) 99m Tc MDP, 2-h to 3-h delay McNemar Takenaka et al 2009 115 Prospective cohort Patient and lesion based 3.3 MBq/kg, uptake 60 min 555 MBq (15 mCi) 99m Tc HMDP, 2-h delay McNemar PET/CT, whole-body SPECT performed Song et al 2009 1000 Retrospective cohort Patient based 550 MBq, uptake 60 min 1110 MBq 99m Tc DPD, 4-h to 6-h delay McNemar PET/CT Min et al 2009 182 Retrospective cohort Patient based 0.14 mCi/kg FDG, uptake 60 min 35–40 mCi 99m Tc MDP, 3-h delay McNemar PET/CT
BS, bone scintigraphy; CT, computed tomography; DPD, diphosphono-propane-dicarbon acid; FDG, 18 F-fluorodeoxyglucose; HMDP, hydroxymethane diphosphonate; MDP, methylene diphosphonate; PET, positron emission tomography; SPECT, single-photon emission computed tomography.
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Methodologic Quality Assessment
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Table 3
Quality Assessment of the Seven Diagnostic Studies Included in the Present Review
Study Year IV Criteria EV Criteria Total IV Score Total EV Score % of Maximum Score IV1 IV2 IV3 IV4 IV5 IV6 EV1 EV2 EV3 EV4 EV5 EV6 Bury et al 1998 + + − − − − + + + + + + 2 6 67 Hsia et al 2002 + − − − − − + + + + − + 1 5 50 Gayed et al 2003 + − − − − − − + + + − + 1 4 42 Cheran et al 2004 + − − − − − + + + + + + 1 6 58 Takenaka et al 2009 + + − − − + − + + + + + 3 5 67 Song et al 2009 + + − − − − + + + + − + 2 5 58 Min et al 2009 + + − − − − + + + + − + 2 5 58
EV, external validity; IV, internal validity; +, score 1; −, score 0.
The full total score was 12, and the percentage of the maximum score was calculated as (total IV score + total EV score)/12 × 100%.
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Diagnostic Accuracy of FDG-PET or PET/CT
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Assessment of Publication Bias and Study Heterogeneity
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Table 4
Covariates of Metaregression Assessing Heterogeneity in Patient-based PET/CT or PET and BS
Possible Confounder Univariate Coefficient (Standard Error)P FDG-PET/CT or PET Year of publication 0.139 (0.0870) .2082 PET/CT performance 1.073 (0.6131) .1783 Sample size 0.406 (0.9030) .6831 Study design −2.343 (1.6923) .2602 BS Year of publication 0.109 (0.0687) .2106 Sample size −0.721 (0.8697) .4682 Study design −1.958 (1.1954) .2000
BS, bone scintigraphy; CT, computed tomography; FDG, 18 F-fluorodeoxyglucse; PET, positron emission tomography.
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Discussion
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Conclusions
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