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

Ming Zhao; Yongfu Ma; Bo Yang; Yuqi Wang

doi:10.4103/0973-1482.200742

ORIGINAL ARTICLE

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

Ming Zhao, Yongfu Ma, Bo Yang, Yuqi Wang
Department of Thoracic Surgery, Chinese PLA General Hospital, 100853 Beijing, China

Date of Web Publication

22-Feb-2017

Correspondence Address:
Yuqi Wang
Department of Thoracic Surgery, Chinese PLA General Hospital, 100853 Beijing
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0973-1482.200742

> 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 2021 Mar 7];12:304-8. Available from: https://www.cancerjournal.net/text.asp?2016/12/8/304/200742

> Introduction

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

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

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

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

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

Nil.

Conflicts of interest

There are no conflicts of interest.

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