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Year : 2016  |  Volume : 12  |  Issue : 8  |  Page : 304-308

A meta-analysis to evaluate the diagnostic value of dual-time-point F-fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis of pulmonary nodules

Department of Thoracic Surgery, Chinese PLA General Hospital, 100853 Beijing, China

Date of Web Publication22-Feb-2017

Correspondence Address:
Yuqi Wang
Department of Thoracic Surgery, Chinese PLA General Hospital, 100853 Beijing
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.200742

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 > Abstract 

Objectives: This meta-analysis aimed at evaluating the efficacy of dual-time-point (DTP) F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in diagnosing pulmonary nodules.
Methods: Using computer and manual search, the current research about the efficacy of DTP F-FDG PET/CT in diagnosing pulmonary nodules was collected. According to the evaluation criteria of Quality Assessment of Diagnostic Accuracy Studies Scale, the data from 13 studies were analyzed by Meta-DiSc software, and the sensitivity (Sen), specificity (Spe), diagnostic odds ratios (DOR), positive likelihood ratios (LR+), and negative likelihood ratios (LR) were summarized.
Results: A total of 13 articles were included in this study, involving 962 patients. The meta-analysis showed that the rough Sen of DTP PET/CT was 0.80 (95% confidence interval [CI] 0.76–0.84, I2 = 83.2%), the summary Spe was 0.75 (95% CI 0.71–0.79, I2 = 89.3%), the summary LR + and LR were 2.57 (95% CI 1.54–4.29) and 0.28 (95% CI 0.16–0.5), respectively, and DOR was 10.01 (95% CI 3.83–26.18).
Conclusion: DTP F-FDG PET/CT has similar Sen and Spe, with single-time-point PET/CT in diagnosing pulmonary nodules. Further high-quality research is required to explore the potential value of DTP F-FDG PET/CT.

Keywords: Dual-time-point positron emission tomography/computed tomography, fluorodeoxyglucose, lung neoplasms, meta-analysis, pulmonary nodules

How to cite this article:
Zhao M, Ma Y, Yang B, Wang Y. A meta-analysis to evaluate the diagnostic value of dual-time-point F-fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis of pulmonary nodules. J Can Res Ther 2016;12, Suppl S4:304-8

How to cite this URL:
Zhao M, Ma Y, Yang B, Wang Y. A meta-analysis to evaluate the diagnostic value of dual-time-point F-fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis of pulmonary nodules. J Can Res Ther [serial online] 2016 [cited 2022 Dec 8];12, Suppl S4:304-8. Available from: https://www.cancerjournal.net/text.asp?2016/12/8/304/200742

 > Introduction Top

It is difficult to differentially diagnose benign and malignant pulmonary nodules in chest imaging diagnosis, and it is closely related to clinical treatment and prognosis. Fluorodeoxyglucose (FDG) positron emission tomography (PET) has been affirmed in many kinds of malignant tumors, and FDG-PET is one of the most widely used clinical indications to evaluate the malignant lung nodules.[1] From the aspects of functional metabolism and anatomical morphology, it has high sensitivity (Sen) and specificity (Spe) that the characteristics of nodules are judged by the use of FDG PET/computed tomography (CT) imaging. Dual-time-point (DTP) PET/CT imaging is performed second time after the conventional imaging. The uptake of two lesions and the standard uptake value (SUV) were diagnosed. The diagnosis was made by the change of the intake of two lesions and SUV. The FDG intake of chronic inflammation and infection tissue cells in a certain period to reduce or change is not obvious. In general, increased glucose utilization can be observed in malignant cells;[2] this might be because the number of glucose transporter proteins,[3] enzyme levels of hexokinase, and phosphofructokinase promoting glycolysis increased.[4] DTP FDG PET imaging may have value in differentiating malignant from benign, and the Spe of FDG PET can be enhanced because different cells have different FDG uptake rates. The aim of this study was to comprehensively evaluate the diagnostic accuracy of DTP PET/CT for the evaluation of pulmonary nodules.

 > Methods Top

Search strategy

To identify eligible studies, we searched the PubMed, EMBASE, EBSCO, and Web of Knowledge databases. We limited the publication time from January 1995 to May 2016 and did the search by Boolean terms based on the combination of keywords: (positron emission tomography OR PET OR PET/CT OR PET-CT OR fluorodeoxyglucose OR FDG) AND (dual time point OR dual phase OR double phase OR delayed phase) AND (lung nodules OR pulmonary nodules). For additional studies, we screened references in the retrieved articles.

Selection criteria

Following are selection criteria involved in this study: (i) to evaluate lung nodules, we use DTP 18 F-FDG PET/CT versus single-time-point imaging; (ii) the reference standards are histopathological analysis and clinical or imaging follow-up; (iii) we calculated absolute numbers of true positive (TP), true negative (TN), false positive (FP), false negative (FN) to construct 2 × 2 tables; (iv) to limit data, we exclude conference abstracts, case reports, letters, and reviews, and we also exclude studies in which patients fewer than 10 or data were unavailable to construct 2 × 2 tables. Furthermore, we also excluded duplicate studies.

Data extraction and quality assessment

The same reviewers conducted a literature search that included data extraction of studies and resolved discrepancies by discussion. For each article, we extracted data about the characteristics of studies, patients, and imaging techniques for the following items: investigators, study population description, publication year, study design (prospective or retrospective), patient registration, modality type. In addition, the absolute numbers of TP, FP, FN, and TN for each included study were extracted at the level of each patient, lesion level, or both.

The quality assessment of the included study in this paper was based on the assessment scale of diagnostic accuracy studies (QUADAS).[5] The QUADAS tool scale includes 14 items, each of which is “yes,” “no,” or “unclear.”

Statistical analysis

For patient-based and lesion-based analysis, we calculated the pooled Sen, Spe, diagnostic odds ratio (DOR), positive likelihood ratio (LR +), negative likelihood ratio (LR), and their 95% confidence intervals (CIs). The summary receiver-operating characteristic (SROC) curves were constructed to assess the interaction between Sen and Spe. In addition, the area under the curve (AUC) and the Q* index were also obtained. Finally, a Z-test was performed to find whether the Sen, Spe, DOR, or the Q* index was significantly different between these two techniques. P < 0.05 was considered statistically significant. The statistical analyses were performed using Meta-DiSc version 1.4 software (The Ramón y Cajal Hospital, Madrid, Spain.).

 > Results Top

Literature search and study description

After the computerized search and a wide range of references, we identified 124 relevant articles. After reviewing the titles and abstracts, 98 were excluded because of their irrelevant topics: (i) not about pulmonary nodules but about another disease; (ii) not about DTP F-FDG PET/CT but about other imaging technique. Another 13 studies were excluded because they contained no original data, for example, reviews, case reports, or letters. After reviewing the full report, the reasons for exclusion could be listed as follows: insufficient data available for the derivation of 2 × 2 tables (n = 10); duplicate studies (n = 2); and other radiotracers used (n = 1). Finally, 13 studies were included in this meta-analysis. Thirteen other studies were excluded. The thirteen studies did not contain raw data. In this study, reasons of exclusion were listed as follows: for 2 × 2 table data export deficiency (n = 10); repetitive studies (n = 2); and other tracers used (n = 1). Finally, 13 studies are included in this meta-analysis [Figure 1].
Figure 1: Selection process

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The characteristics of the including study are shown in [Table 1]. A total of 962 patients were included in the analysis, ranging aged from 32 to 87 years. Four studies were enrolled patients prospectively, and nine studies were enrolled retrospectively. In addition, the patient selection in two studies did not report their age information. The median time of the image was 60 min (range, 45–65 min) after early scanning and 120 min injection (range, 110–180 min) on delayed scan in most studies.
Table 1: The characteristics of the included studies

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Quality assessment

Methodological quality using QUADAS tool consists of nine projects which are evaluated, including representative spectra,[1] clear choice standard,[2] acceptable reference standard (item 3), disease progression verify (item 5),[4] same benchmark index measuring outcomes (item 6), bias (item 7), with the test index detailed reference standard.[8],[9] Detailed results are shown in [Table 2].
Table 2: Quality assessment

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Summary of diagnostic accuracy

Statistical results are shown in [Figure 2]. Overall Spe was 0.75 (0.71 to 0.79) and Overall Sen was 0.80 (0.76 to 0.84) in this study of patient data. The Sen and Spe of DTP PET/CT were significantly higher than those of STP imaging (P < 0.05) [Figure 2]a and [Figure 2]b. The summary LR + and LR were 2.57 (95% CI 1.54–4.29) and 0.28 (95% CI 0.16–0.5), respectively, and DOR was 10.01 (95% CI 3.83–26.18) in [Figure 2]c,[Figure 2]d,[Figure 2]e.
Figure 2: (a) Pooled specificity, (b) pooled sensitivity,(c) pooled LR+,(d) pooled LR, (e) pooled diagnostic odds ratio

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The SROC curves are shown in [Figure 3]. For DTP PET/CT, the AUC and Q* index were 0.8426 and 0.7742, respectively, and for STP imaging, these values were 0.0543 and 0.0506, respectively. The AUC and Q* index of DTP were higher than those of STP (P < 0.05).
Figure 3: Summary receiver-operating characteristic curve

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 > Discussion Top

DTP 18 F-FDG PET/CT imaging is used to identify benign and malignant lung nodules on the basis of the diagnosis of malignant tumor cells on the peak of 18 F-FDG uptake in 4–5 h.[19] Malignant tumor in the standard scan minimum 45–60 after second time of delay scanning, the focus of the SUV should be increased, while the benign lesions SUV should reduce or increase is not obvious.[20] However, the clinical value of DTP 18 F-FDG PET/CT imaging in the differential diagnosis of pulmonary nodules has been controversial. The efficacy of dual-phase PET/CT in the diagnosis of pulmonary nodules was not significantly superior to that of single-phase PET/CT compared with previous studies, and the results were similar to those of previous studies.[21],[22],[23],[24] In this paper, the causes of heterogeneity may be due to the small sample size, size of the lesion, degree of malignancy, FDG activity, time of the examination, and so on. In addition, the different methods and standards of image analysis and the setting of threshold value and reference standard can also produce heterogeneity. Limitations or potential bias of this study: this paper included fewer articles, only 13 articles, the sample size was small; this paper only includes the English literature, there may be language bias; included in the study of the scanning parameters, delay time, and other technical aspects of the difference, if the use of a unified scanning scheme, the results will be more convincing; FDG is not tumor specific, and its intake is influenced by many factors, such as the level of plasma glucose, the height of the patient, and the weight of the patient; in this paper, the impact of large sample study at meta-analysis is larger than that of small sample, which also has potential bias.

 > Conclusion Top

Dual-phase PET/CT in the diagnosis of pulmonary nodules is similar to the single-time PET/CT; there were no obvious advantages; conventional differential diagnosis of lung benign and malignant nodules is not recommended to use a dual-phase PET/CT. we need higher quality and large sample research to further explore the potential of the dual-phase PET/CT.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Rohren EM, Turkington TG, Coleman RE, editors. Clinical Applications of PET in Oncology. “Application and Research Progress of Molecular Nuclear Medicine in the Diagnosis and Treatment of Tumor” Academic Exchange Meeting of Research and Methodology of Research and Methodology of Tumor Molecular Markers in China; 2006.  Back to cited text no. 1
Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Mazière B. FDG accumulation and tumor biology. Nucl Med Biol 1998;25:317-22.  Back to cited text no. 2
Flier JS, Mueckler MM, Usher P, Lodish HF. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 1987;235:1492-5.  Back to cited text no. 3
Monakhov NK, Neistadt EL, Shavlovskil MM, Shvartsman AL, Neifakh SA. Physicochemical properties and isoenzyme composition of hexokinase from normal and malignant human tissues. J Natl Cancer Inst 1978;61:27-34.  Back to cited text no. 4
Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529-36.  Back to cited text no. 5
Alkhawaldeh K, Bural G, Kumar R, Alavi A. Impact of dual-time-point (18) F-FDG PET imaging and partial volume correction in the assessment of solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2008;35:246-52.  Back to cited text no. 6
Cloran FJ, Banks KP, Song WS, Kim Y, Bradley YC. Limitations of dual time point PET in the assessment of lung nodules with low FDG avidity. Lung Cancer 2010;68:66-71.  Back to cited text no. 7
Xiu Y, Bhutani C, Dhurairaj T, Yu JQ, Dadparvar S, Reddy S, et al. Dual-time point FDG PET imaging in the evaluation of pulmonary nodules with minimally increased metabolic activity. Clin Nucl Med 2007;32:101-5.  Back to cited text no. 8
Suga K, Kawakami Y, Hiyama A, Sugi K, Okabe K, Matsumoto T, et al. Dual-time point 18F-FDG PET/CT scan for differentiation between 18F-FDG-avid non-small cell lung cancer and benign lesions. Ann Nucl Med 2009;23:427-35.  Back to cited text no. 9
Schillaci O, Travascio L, Bolacchi F, Calabria F, Bruni C, Cicciò C, et al. Accuracy of early and delayed FDG PET-CT and of contrast-enhanced CT in the evaluation of lung nodules: A preliminary study on 30 patients. Radiol Med 2009;114:890-906.  Back to cited text no. 10
Sathekge MM, Maes A, Pottel H, Stoltz A, van de Wiele C. Dual time-point FDG PET-CT for differentiating benign from malignant solitary pulmonary nodules in a TB endemic area. S Afr Med J 2010;100:598-601.  Back to cited text no. 11
Núñez R, Kalapparambath A, Varela J. Improvement in sensitivity with delayed imaging of pulmonary lesions with FDG-PET. Rev Esp Med Nucl 2007;26:196-207.  Back to cited text no. 12
Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18F-FDG PET for the evaluation of pulmonary nodules. J Nucl Med 2002;43:871-5.  Back to cited text no. 13
Chen CJ, Lee BF, Yao WJ, Cheng L, Wu PS, Chu CL, et al. Dual-phase 18F-FDG PET in the diagnosis of pulmonary nodules with an initial standard uptake value less than 2.5. AJR Am J Roentgenol 2008;191:475-9.  Back to cited text no. 14
Laffon E, de Clermont H, Begueret H, Vernejoux JM, Thumerel M, Marthan R, et al. Assessment of dual-time-point 18F-FDG-PET imaging for pulmonary lesions. Nucl Med Commun 2009;30:455-61.  Back to cited text no. 15
Macdonald K, Searle J, Lyburn I. The role of dual time point FDG PET imaging in the evaluation of solitary pulmonary nodules with an initial standard uptake value less than 2.5. Clin Radiol 2011;66:244-50.  Back to cited text no. 16
Lan XL, Zhang YX, Wu ZJ, Jia Q, Wei H, Gao ZR. The value of dual time point (18) F-FDG PET imaging for the differentiation between malignant and benign lesions. Clin Radiol 2008;63:756-64.  Back to cited text no. 17
Kim IJ, Kim SJ, Kim YS, Lee TH, Jeong YJ. Characterization of pulmonary lesions with low F-18 FDG uptake using double phase F-18 FDG PET/CT: Comparison of visual and quantitative analyses. Neoplasma 2009;56:33-9.  Back to cited text no. 18
Hamberg LM, Hunter GJ, Alpert NM, Choi NC, Babich JW, Fischman AJ. The dose uptake ratio as an index of glucose metabolism: Useful parameter or oversimplification? J Nucl Med 1994;35:1308-12.  Back to cited text no. 19
Chen CJ, Lee BF, Yao WJ, Cheng L, Wu PS, Chu CL, et al. Dual-phase 18F-FDG PET in the diagnosis of pulmonary nodules with an initial standard uptake value less than 2.5. AJR Am J Roentgenol 2008;191:475-9.  Back to cited text no. 20
Jennison RF, Komrower GM. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions. JAMA 2001;285:914-24.  Back to cited text no. 21
Zhang L, Wang Y, Lei J, Tian J, Zhai Y. Dual time point 18FDG-PET/CT versus single time point 18FDG-PET/CT for the differential diagnosis of pulmonary nodules: A meta-analysis. Acta Radiol 2013;54:770-7.  Back to cited text no. 22
Barger RL Jr., Nandalur KR. Diagnostic performance of dual-time 18F-FDG PET in the diagnosis of pulmonary nodules: A meta-analysis. Acad Radiol 2012;19:153-8.  Back to cited text no. 23
Lin YY, Chen JH, Ding HJ, Liang JA, Yeh JJ, Kao CH. Potential value of dual-time-point 18F-FDG PET compared with initial single-time-point imaging in differentiating malignant from benign pulmonary nodules: A systematic review and meta-analysis. Nucl Med Commun 2012;33:1011-8.  Back to cited text no. 24


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

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