Diagnostic Accuracy of 18F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis

doi:10.1016/j.acra.2013.09.015

Academic Radiology

Volume 21, Issue 1, January 2014, Pages 11-20

https://doi.org/10.1016/j.acra.2013.09.015 Get rights and content

Rationale and Objectives

To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions.

Methods and Materials

A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of ¹⁸F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR−) and diagnostic odds ratio (DOR) of ¹⁸F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient–based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed.

Results

Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92–97%), specificity 82% (95%CI: 76–88%), LR+ 5.3 (95%CI: 2.4–11.8), LR− 0.09 (95%CI: 0.05–0.14), DOR 74 (95%CI: 34–161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found.

Conclusions

¹⁸F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.

Section snippets

Methods

This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement that describes an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses (8).

Literature Search

The comprehensive computer literature search from PubMed/MEDLINE and Scopus databases revealed 540 articles. Reviewing titles and abstracts, 524 articles were excluded: 464 because they were not in the field of interest of this review, 8 because they were evaluating the diagnostic performance of ¹⁸F-FDG-PET or PET/CT in assessing pleural lesions in patients with history of cancer 13, 14, 15, 16, 17, 18, 19, 20, 35 because they were reviews or editorials, 15 because they case reports, and 2

Discussion

To the best of our knowledge, this systematic review and meta-analysis is the first to evaluate the diagnostic accuracy of ¹⁸F-FDG-PET or PET/CT in the differential diagnosis between malignant and benign pleural lesions. Several studies have used ¹⁸F-FDG-PET or PET/CT in this setting, reporting different values of sensitivity and specificity (Table 3). However, many of these studies have limited power, analyzing only relatively small numbers of patients. To derive more robust estimates of the

Conclusions

References (40)

N.R. Qureshi et al.
Imaging of pleural disease
Clin Chest Med
(2006)
M. Metintas et al.
Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases
Eur J Radiol
(2002)
M. Metintas et al.
Local recurrence of tumor at sites of intervention in malignant pleural mesothelioma
Lung Cancer
(2008)
G. Treglia et al.
Recent applications of nuclear medicine in diagnostics (first part)
Ital J Med
(2010)
B. Duysinx et al.
Contribution of positron emission tomography in pleural disease
Rev Mal Respir
(2010)
A. Liberati et al.
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration
J Clin Epidemiol
(2009)
N.C. Gupta et al.
Clinical role of F-18 fluorodeoxyglucose positron emission tomography imaging in patients with lung cancer and suspected malignant pleural effusion
Chest
(2002)
F. Bénard et al.
Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography
Chest
(1998)
B. Duysinx et al.
Evaluation of pleural disease with 18-fluorodeoxyglucose positron emission tomography imaging
Chest
(2004)
H. Yildirim et al.
Clinical value of fluorodeoxyglucose-positron emission tomography/computed tomography in differentiation of malignant mesothelioma from asbestos-related benign pleural disease: an observational pilot study
J Thorac Oncol
(2009)

U. Elboga et al.

The role of FDG PET-CT in differential diagnosis of pleural pathologies

Rev Esp Med Nucl Imagen Mol

(2012)

B. Feragalli et al.

Malignant pleural disease

Radiol Med

(2003)

R. Francis et al.

Novel molecular imaging in lung and pleural diseases

Respirology

(2011)

Oxford Center for Evidence-Based Medicine checklist for diagnostic studies appraisal. Available at:...

M. Egger et al.

Bias in meta-analysis detected by a simple, graphical test

BMJ

(1997)

S. Duval et al.

Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis

Biometrics

(2000)

J. Zamora et al.

Meta-DiSc: a software for meta-analysis of test accuracy data

BMC Med Res Methodol

(2006)

J.J. Erasmus et al.

FDG PET of pleural effusions in patients with non-small cell lung cancer

AJR Am J Roentgenol

(2000)

G.J. Schaffler et al.

Non-small cell lung cancer: evaluation of pleural abnormalities on CT scans with 18F FDG PET

Radiology

(2004)

J.S. Toaff et al.

Differentiation between malignant and benign pleural effusion in patients with extra-pleural primary malignancies: assessment with positron emission tomography-computed tomography

Invest Radiol

(2005)

Cited by (44)

A PET-CT score for discriminating malignant from benign pleural effusions
2023, Medicina Clinica
The results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions.
We conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021.
One hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV > 7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV > 4.5 (5 points) and cardiomegaly (−1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients.
PET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.
Los estudios PET-TAC previos en el análisis del derrame pleural son contradictorios. Nuestro objetivo es desarrollar una puntuación mediante PET-TAC para diferenciar entre derrames benignos y malignos.
Estudio prospectivo en pacientes con derrame pleural a los que se realizó una PET-TAC desde octubre de 2013 hasta octubre de 2019 (cohorte de referencia). Los datos analizados fueron: engrosamiento lineal; engrosamiento nodular; nódulos; masas; engrosamiento circunferencial; afectación pleural mediastínica y cisural; ganglios linfáticos torácicos; loculación pleural; consolidación; calcificación pleural; cardiomegalia; derrame pericárdico; derrame bilateral; masa pulmonar; metástasis hepáticas y otras neoplasias malignas extrapleurales. Se calculó el SUV de todos estos parámetros. Los resultados se validaron en una cohorte independiente.
Se incluyó a 199 pacientes en la cohorte de referencia (91 derrames malignos y 108 benignos). Los parámetros que mostraron más utilidad para discriminar ambos derrames y desarrollar una puntuación fueron: engrosamiento pleural nodular, nódulos pleurales con SUV > 7,5, masa pulmonar o malignidad extrapleural (10 puntos cada uno), ganglio en cadena mamaria con SUV > 4,5 (5 puntos) y cardiomegalia (–1 punto). Con un punto de corte > 9 en la cohorte de derivación, se estableció el diagnóstico de derrame pleural maligno con una sensibilidad del 87,9%, especificidad del 90,7%, valor predictivo positivo del 88,9%, valor predictivo negativo del 89,9% razón de verosimilitud positiva del 7,81 y razón de verosimilitud negativa del 0,106. Estos resultados fueron validados en una cohorte prospectiva independiente de 75 pacientes.
Una puntuación basada en PET-TAC proporciona información relevante para el diagnóstico del derrame pleural maligno.
Positron emission tomography-computed tomography (PET-CT) in suspected malignant pleural effusion. An updated systematic review and meta-analysis
2021, Lung Cancer
Citation Excerpt :
In subgroup analysis, the authors found no change in the diagnostic value of PET/PET-CT in patients with known malignancy, which is in contrast to parts of our results, probably due to considerable and unadjusted heterogeneity. Treglia et al concluded that FDG PET/PET-CT is an accurate diagnostic imaging method in the differential diagnosis between malignant and non-malignant pleural lesions including effusions [24]. The review included sixteen studies with 745 patients.
The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions.
A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned.
Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR + ) and negative likelihood ratio (LR-) of 9.9 (4.5–15.3) respectively 0.1 (0.1–0.2). There was considerable heterogeneity among studies.
In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias.
Clinical Trial Registration: The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020.
Updates in Pleural Imaging
2021, Clinics in Chest Medicine
Imaging of the Pleura: CT, MRI and PET
2021, Encyclopedia of Respiratory Medicine, Second Edition
Despite the development of thoracic ultrasound, there remains a crucial role for three-dimensional cross-sectional imaging in the investigation and management of pleura disease. Traditionally this has been in the form of computed tomography (CT) which has become established as a common imaging modality in routine standard practice, however the roles of magnetic resonance imaging (MRI) and positron emission tomography in imaging the pleura are increasing and becoming superiorly defined. The mechanisms, roles and utilities of all three modalities in common elements of pleural disease are explored in this article.
Medical thoracoscopy in respiratory medicine: The Liège University Hospital experience
2019, Revue des Maladies Respiratoires
L’incidence des maladies de la plèvre continue à augmenter à travers le monde. La thoracoscopie médicale demeure l’examen de référence dans l’exploration de la cavité pleurale.
Nous rapportons l’évaluation rétrospective, l’efficacité et les complications observées des 1024 thoracoscopies médicales adressées au CHU de Liège entre 2000 et 2017.
Cent pneumothorax, 400 atteintes pleurales bénignes et 501 malignes ont été colligées. L’indication première de la thoracoscopie demeure l’exploration d’une pleurésie exsudative lymphocytaire d’étiologie inconnue après thoracocentèse. Sa sensibilité diagnostique était de 99,2 % dans l’identification d’une pleuropathie maligne. Une pleurodèse au talc a été réalisée dans 69,5 % de la population globale et chez 66,1 % des atteintes pleurales solides ou liquidiennes. Un échec de pleurodèse a été observé dans 11 % des patients présentant un pneumothorax récidivant et chez 7,8 % des pleurésies néoplasiques talquées. Une mortalité de 0,6 % à 30 jours, un drainage prolongé dans 8,3 %, et 4,7 % de complications graves ont été colligés. Au total, 22/1024 (2,1 %) des thoracoscopies n’ont pu être réalisées en raison d’une fibrose pleurale non dissécable.
La thoracoscopie médicale est un examen simple et bien toléré. Elle présente une excellente rentabilité dans la prise en charge diagnostique et thérapeutique des maladies pleurales.
The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity.
We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017.
In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis.
The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis.
Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease.
Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy
2018, Lung Cancer
Citation Excerpt :
Recent meta-analyses have demonstrated a pooled sensitivity of 81% and specificity 74% for detecting PM, with considerable variation between studies [11]. Tumours with low metabolic activity, such as early stage epithelioid MPM are more likely to have a false negative PET-CT and false positives in patients with inflammatory pleuritis, TB pleuritis and previous pleurodesis are well recognised [12–14]. Efficient diagnosis is further complicated by the variable performance of pleural cytology, which has a mean sensitivity of 60% (depending on tumour type) but extremely low negative predictive value (NPV) in MPM, for which histological confirmation remains mandatory in most centres.
Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening.
60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma.
71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61–94%), specificity 83% (95% CI 68–91%), positive predictive value 68% (95% CI 47–84%), negative predictive value 92% (78–97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02).
ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.

View all citing articles on Scopus

View full text

Original InvestigationDiagnostic Accuracy of 18F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis

Rationale and Objectives

Methods and Materials

Results

Conclusions

Section snippets

Methods

Literature Search

Discussion

Conclusions

Clin Chest Med

Eur J Radiol

Lung Cancer

Ital J Med

Rev Mal Respir

J Clin Epidemiol

Chest

Chest

Chest

J Thorac Oncol

Rev Esp Med Nucl Imagen Mol

Malignant pleural disease

Radiol Med

Novel molecular imaging in lung and pleural diseases

Respirology

Bias in meta-analysis detected by a simple, graphical test

BMJ

Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis

Biometrics

Meta-DiSc: a software for meta-analysis of test accuracy data

BMC Med Res Methodol

FDG PET of pleural effusions in patients with non-small cell lung cancer

AJR Am J Roentgenol

Non-small cell lung cancer: evaluation of pleural abnormalities on CT scans with 18F FDG PET

Radiology

Differentiation between malignant and benign pleural effusion in patients with extra-pleural primary malignancies: assessment with positron emission tomography-computed tomography

Invest Radiol

Original Investigation
Diagnostic Accuracy of ¹⁸F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis