Lithuanian University of Health Sciences Faculty of medicine
Department of Nuclear medicine
The Value of Positron Emission Tomography (PET/CT) in Differential
Diagnosis of Solitary Pulmonary Nodules
(literature review)
Master thesis of the medical integrated master’s study programme of the medical academy’s faculty of medicine of the Lithuanian University of Health Sciences
Author: Gabriel Oshana
Supervisor: Prof.Ilona Kulakienė
Year of the thesis preparation: 2018-2020
Table of Contents
SUMMARY 3
CONFLICTS OF INTEREST 4
CLEARANCE ISSUED BY THE ETHICS COMMITTEE 5
ABBREVIATIONS 6
TERMS 7
INTRODUCTION 8
LITERATURE REVIEW METHODOLOGY AND METHODS 9
LITERATURE REVIEW 11
Results 18
DISCUSSION OF THE RESULTS 21
CONCLUSIONS 26
SUMMARY
Author’s name and surname: Gabriel Oshana
The title of the literature review: The Value of Positron Emission Tomography (PET/CT) in Differential Diagnosis of Solitary Pulmonary Nodules
The literature review aims to determine the value of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scan in the differential diagnosis of solitary pulmonary nodules.
The objective was to collect, review, and analyze studies conducted to determine the value of 18F-FDG-PET/CT in the differential diagnosis of solitary pulmonary nodules, and to determine the disorders behind false-positive results.
Methodology: PubMed database was systematically searched from 2013 to 2018 for studies of 18F-FDG-PET/CT in the differential diagnosis of Solitary pulmonary nodules (SPNs), and data on the sensitivity and specificity were collected and analyzed.
Study design: The following search terms were used “18F-FDG-PET/CT” OR “FDG-PET/CT” AND “solitary pulmonary nodules” AND “sensitivity” AND “specificity” AND “diagnosis”. Inclusion criteria involved, articles that were written in English language, patients with solitary pulmonary nodules were diagnosed by 18F-FDG-PET/CT imaging, and sensitivity and specificity values were presented. Exclusion criteria involved data that was not published, case reports, letters to the editor, abstracts, and review articles. Forty-four articles were found, of which eighteen were excluded, 26 articles were included.
Research results: Sensitivity values for 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules ranged from 64%-100%, and specificity ranged from 29%-96% in 26 publications, Majority causes of false-positive results were infective and inflammatory lesions.
CONFLICTS OF INTEREST
ABBREVIATIONS
1. SPN - solitary pulmonary nodule
2. 18F-FDG-PET/CT or 18F-FDG-PET/CT - 18-fluorodeoxyglucose-positron emission
tomography/computed tomography
3. SUVmax - maximum standardized uptake value 4. CECT - contrast-enhanced computed tomography 5. DTPI - dual-time point imaging
TERMS
INTRODUCTION
Solitary pulmonary nodules (SPNs) are round opaque lung lesions with a diameter of <3cm; they are surrounded by lung parenchyma without any associated disease of the lymph nodes, complete or partial collapse of the lung, or infection of the lungs [1]. Lung lesion >3 cm is a lung mass, bronchogenic carcinoma in origin until proven. SPNs are found approximately 0.2% to 2 % of all performed chest x-rays and around 10% to 40% of all computed tomography scans [2]. The use of Computed tomography has increased the findings of SPNs because of its higher resolution than conventional radiography [3]. The role of radiological imaging techniques in SPN diagnosis is to differentiate malignant from benign lesions to plan further management of the condition. Their morphological features differentiate benign and malignant lesions; however, some lesions display a combination of both features and do not present with specific clinical symptoms making diagnosis difficult [3]. It is essential to identify malignant and benign lesions early for successful treatment, management, and prognosis. A tissue biopsy sample is considered the best standard for SPN diagnosis; however, it is an invasive procedure, carries significant risks for the patients and requires skilled physicians for acquiring [3]. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is a hybrid noninvasive imaging that combines computed tomography
with positron emission tomography to diagnose SPNs. It adds a radio-labeled tracer fluorodeoxyglucose (18F-FDG) that accumulates in malignant, infectious, inflammatory, autoimmune,
and granulomatous diseases to diagnose pulmonary nodules. It has been proven in some studies to be an adequate noninvasive procedure to distinguish between malignant and benign solitary pulmonary nodules with high sensitivity and high specificity [4]. On the other hand, other publications have reported low sensitivity, specificity values of18F-FDG-PET/CTin SPN diagnosis [5]. This variability
in sensitivity and specificity of 18F-FDG-PET/CT is mainly due to different disorders that cause
false-positive or false-negative results with inflammatory and infective lesions being the leading cause of false-positive results [5]. This literature review describes the classification, characteristics of SPNs, clinical evaluation of patients presenting with SPN, and the diagnostic performance of PET/CT in SPN diagnosis, by searching for, reviewing, and analyzing 26 related studies. To specify if
18F-FDG-PET/CT can replace the standard invasive method of SPN diagnosis and its clinical
LITERATURE REVIEW METHODOLOGY AND METHODS
AIM OF THE THESIS:The literature review aims to determine the value of18F-FDG-PET/CT scan in differentiating malignant from benign solitary pulmonary nodules.
OBJECTIVE OF THE THESIS:
1. Collect literature data aimed at determining the value of positron emission tomography (PET/CT) in the differential diagnosis of solitary pulmonary nodules
2. Analyze sensitivity and specificity results 3. Determine the cause of false-positive results
RESEARCH PLANNING (ORGANIZATION)
In this literature review, the classification, characteristics and the clinical evaluation of patients presenting with SPN are described. The value of PET/CT in the differential diagnosis of solitary pulmonary nodules is determined by searching for, reviewing, and analyzing 26 related studies.
PARTICIPANT SELECTION (POPULATION, SAMPLE)
patients had an 18F-FDG-PET/CT imaging examination performed; the articles presented with values of sensitivity specificity, and the articles were written in the English language. Exclusion criteria included data that was not published, case reports, letters to the editor, abstracts, and review articles. This study did not require ethical approval or patient consent since this literature review, is of previously published articles. The following information was collected from the articles, first author, year of publication, numbers of cases, sensitivity, specificity disorders of false- positives results.
METHODS OF DATA ANALYSIS
LITERATURE REVIEW
Characteristics and classification of solitary pulmonary nodules:
SPNs are classified into four groups; infectious, inflammatory diseases, vascular neoplasms, and malignancies group. The first step in diagnosing SPNs is evaluating their morphological characteristics; size, margin, density calcification, and enhancement features [3]. An example of a clinical presentation of characteristics typical to benign lesions would be, a smooth non-enhancing nodule 1cm in size with intra-nodular fat, in a 22-year-old patient. An example of a clinical presentation of a malignant lesion would be a speculated non-calcified nodule with enhancement, three cm in size found in a 64-year old male patient with a long history of smoking. However, sometimes some lesions present with a combination of typical benign and malignant features making diagnosis more challenging [3].
Clinical evaluation of the patients presenting with solitary pulmonary nodules:
artifact; hence it is not recommended for the evaluation of solitary pulmonary nodules [3]. The traditional noninvasive methods are not satisfactory in separating benign from malignant nodules because they only evaluate nodule morphology. The new noninvasive diagnostic techniques in the evaluation of SPNs are PET and PET／ CT [3]. Performance indicators of PET/CT value for SPN diagnosis are sensitivity and specificity. The percentages, causes of SPNs, heterogeneity of the patient population, PET techniques, number of undiagnosed patients in the studies vary, making comparison difficult.
Application value of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET／CT) in the Evaluation of Solitary Pulmonary Nodules
Garcia et al. [7] used FDG PET/CT to characterize 64 baseline lung nodules >10mm in size and 36 incidence nodules. The nodules were detected on low-dose CT screening in asymptomatic current or former smokers at high risk for lung cancer. Thirty-one malignant tumors were accurately identified by FDG PET/CT and were falsely negative in 6 patients. The sensitivity, specificity, of visual analysis to detect malignancy was 84% and 95%, respectively.
Zhao et al. [8] studied One hundred thirty-nine patients with solitary pulmonary lesions, 89 malignant, and 50 benign lesions. Maximum standardized uptake value (SUVmax) reflects the amount of 18F-FDG uptake by lesions to differentiate between benign and malignant nodules. However, this amount changes from different institutions. In this study, in cases with SUVmax ≥2.5, the false-positive rate was 16%. The false-negative rates were 17.6%, with SUVmax <2.5. The sensitivity and specificity of the method using (18)F-FDG uptake feature combined with SUVmax and the single SUV method were 88.7%/91.0%, and 73.4%, 80.6% respectively.
Veronesi et al. [9] analyzed 383 nodules, 196 of which were malignant. The sensitivity and specificity of PET-CT for differential diagnosis of SPNs were, respectively, 64%, 89%. Overall performance was lower for nodules found at annual repeat scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules.
Evangelista et al. [11] performed FDG PET/CT on fifty-nine patients with indeterminate lung nodules on CT for lesion characterization. Thirty-one patients reported with solitary pulmonary nodules. PET/CT reported 13 true positives, 12 true negatives, one false positive, and five false negatives. The sensitivity and specificity were 72% and 92%, respectively.
Opoka et al. [12] conducted a study on a group of 82 patients. Malignancy was documented in 40 patients (48.8%). SUV(max) values exceeding 2.5 were found in 38 cancer patients (true positives, TP) for which the mean value of SUV(max) was 9.1 (1-26.8). Forty-two lesions were documented as benign (51.2%). SUV(max) values equal to or less than 2.5 were found in 37 patients (true negatives, TN). False-negative results concerned two patients, with the final diagnosis of carcinoid and adenocarcinoma; false-positive results were obtained in 5 patients with various inflammatory lesions. The diagnostic value of PET-CT SUV(max) exceeding 2.5 in the prediction of neoplastic origin of solitary pulmonary lesions was sensitivity 95%, specificity 88%.
Sim et al. [13] correlated SUVmax value with the pathology of SPN and assessed diagnostic accuracy in differentiating malignant from a benign nodule, using 2.5 as threshold SUVmax. A total of 641 PET-CTs were performed for SPN characterization and staging; 186 patients (77 males, 109 females) with pathological confirmation were included, and 158 (85%) nodules were malignant: adenocarcinomas (n = 66), squamous cell carcinomas (n = 40), and metastases (n = 20) were the commonest. 28 lesions (15 %) were benign, including granuloma/chronic inflammation (n = 8), infection (n = 7), and hamartomas (n = 5). cutoff SUVmax of 2.5, yielded sensitivity 86.7 %, and specificity 50 %.
Sebro et al. [14] evaluated the performance of PET/CT for SPN diagnosis in an area of endemic granulomatous diseases using threshold maximum standardized uptake value (max SUV) of 2.5 as a cutoff level for malignancy. Sixty-one of seventy-two lesions were malignant. The false-negative rate was 4.9 %, and the false-positive rate was 54.5 %. The false negatives had a mean max SUV of 2.0, whereas the false positives had a mean max SUV of 5.6. Higher max SUV was significantly associated with increased risk of malignancy. A threshold max SUV of 2.5 had a sensitivity of 95.1 %, and a specificity of 45.5 %. In an area of endemic granulomatous disease, the PET/CT threshold max SUV of 2.5 retained a high sensitivity (95.1 %) for differentiating benign from malignant pulmonary lesions; however, the specificity (45.5) decreased due to increased false positives.
analyzed PET/CT studies by the 5-point visual scale of FDG uptake compared to blood pool and lung tissue, and CT characteristics were determined. PET/CT reported a sensitivity of 100% and specificity 29%.
Application value of single time point imaging (STPI) and dual time point imaging (DTPI) 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET／ CT) in the evaluation of Solitary Pulmonary Nodules
In the evaluation of SPN by 18F-FDG PET/CT, SUV (Standardized Uptake Value) ≥2.5 is frequently used as a cutoff point of a criterion for malignancy. However, FDG is not tumor-specific; some benign lesions such as pulmonary tuberculosis, inflammatory lesions can have high FDG uptake [3]. Moreover, many malignant tumors, such as well-differentiated adenocarcinoma and bronchoalveolar carcinoma, may show only minimal uptake [13]. Some authors have claimed that dual-phase 18F-FDG PET ／ CT scan can improve the accuracy of FDG PET because it shows increased SUV overtime in malignant lesions and decreased or stable SUV overtime in benign lesions. Chen et al. [5] retrospectively reviewed SPN patients who received early and delayed (18)F-FDG PET/CT at 60min and 180min post-injection in granuloma-endemic regions. The study included one-hundred-forty-nine patients. Blinded interpretations performed by physicians were based on single-time point imaging (STPI) PET/CT, dual-time point imaging (DTPI) PET/CT images, and CT images, respectively, and gave a three 5-point visual scale score. The differences of sensitivity, and specificity, between STPI PET/CT sensitivity 82%, specificity 65%, and DTPI PET/CT sensitivity 79%, specificity 71% were not significantly different in visual interpretation. Using SUVmax > 2.5 g/ml, sensitivity was 83% and specificity 48% for STPI PET/CT and 85% sensitivity, 38% specificity for DTPI PET/CT. In granuloma-endemic regions, the differential diagnosis of solitary pulmonary nodules by DTPI PET/CT AND STPI PET/CT, by quantitative analysis and visual interpretation methods showed no significant difference in PET/CT performance.
Comparison of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) with other imaging techniques in the evaluation of solitary pulmonary nodules
In a study by Dabrowska et al. [19], 71 patients were included in the final analysis and were scheduled for contrast-enhanced computed tomography (CECT) and FDG-PET/CT. Twenty-two nodules (31%) were malignant, whereas forty-nine nodules were benign. For discriminating between benign and malignant lesions, an enhancement indicator of 19 Hounsfield unit by CECT was 19 Hounsfield units, the sensitivity, specificity, were 100%, 37%. With the SUV max of 2.1 as the optimal cutoff value for SPN diagnosis, the sensitivity, specificity were 77%, and 92%. The diagnostic accuracy of FDG-PET/CT was higher than that of CECT. The advantage of CECT was its high sensitivity.
Ohno et al. [20] compared the performance of dynamic perfusion area-detector computed tomography, dynamic magnetic resonance imaging, and 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules. There were 218 nodules; all nodules underwent dynamic magnetic resonance imaging, FDG PET/CT, dynamic perfusion area-detector computed tomography, micro bacterial, and pathologic examinations. The specificity of perfusion area-detector computed tomography was significantly higher than those of dynamic magnetic resonance imaging and FDG-PET/CT in the diagnosis of solitary pulmonary nodules of 83%, 68%, and 28%, respectively. Sensitivity values did not significantly differ with values of 93%, 92%, and 90% for perfusion area-detector computed tomography, dynamic magnetic resonance imaging, and PET/CT, respectively.
Results
Sensitivity values for 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules ranged from 46% to 100% in 26 publications. Specificity ranged from 13% to 97%. The majority causes of false-positive results in studies that mentioned the cause of false-positive results were infective and inflammatory diseases, specifically tuberculosis and inflammation-induced granuloma structures.
Study characteristics
Results of sensitivity and specificity of 2441 nodules were collected and analyzed. Solitary pulmonary nodules in the collected studies were <3cm in diameter, surrounded by normal lung tissue, and were diagnosed by histology or follow-up. Maximum standardized uptake values (SUVmax) differed among studies.
Table 1. Characteristics of the studies of 18-fluorodeoxyglucose-positron emission tomography/computed tomographyin the Evaluation of Solitary Pulmonary Nodules
№ Author Year N Sensitivity (%) Specificity (%)
9. Van Gómez López et al. [17] 2015 55 97.5 13.1 10. Veronesi et al. [9] 2015 378 64.0 89.0 11. Li et al. [10] 2014 298 80.2 38.0 12. Evangelista et al. [11] 2014 31 72.0 92.0 13. Opoka et al. [12] 2014 82 95.0 88.0 14. Sim et al. [13] 2013 186 86.7 50.0 15. Sebro et al. [14] 2013 72 95.1 45.5
№, number; N, number of nodules; TP, true-positive; FP, false-positive; TN, true-negative; FN, false-negative.
Table 2. Characteristics of the studies of single time point imaging (STPI) and dual time point imaging (DTPI) 18-fluorodeoxyglucose-positron emission tomography/computed tomography in the evaluation of Solitary Pulmonary Nodules
№ Author Year N Sensitivity (%) Specificity (%)
1. Chen et al. [5] STPI 2016 149 82 65 2. Chen et al. [5] DTPI 2016 149 79 71 3. Demir et al. [18] STPI 2014 48 94 77 4. Demir et al. [18] DTPI 2014 48 100 80
Table 3. Characteristics of the studies comparing 18-fluorodeoxyglucose-positron emission tomography/computed tomography with other imaging techniques in the evaluation of solitary pulmonary nodules
№ Author Year N Sensitivity (%) Specificity (%)
3. Ohno et al. [15] 18F-FDG PET／CT 2015 218 90 28 4. Ohno et al. [20] CT 2015 218 93 83 5. Ohno et al. [20] MRI 2015 218 92 68 6. Ren et al. [21] 18F-FDG PET ／CT 2017 267 80.4 68.1 7. Ren et al. [21] 18F-FDG PET ／ CT + thin CT 2017 267 91.4 79.5
Table 4. Most common causes of false positive results of 18-fluorodeoxyglucose-positron emission tomography/computed tomography scan
№ Author Most common
pathology of false positive results Total number of false-positive results Median SUVmax value
1. Chen et al. [5] Tuberculosis and
granuloma 25 >2.5
2. Zhao et al. [8] Inflammatory
pseudotumor 29 >2.5
3. Opoka et al. [12] Inflammatory
lesions 5 >2.5
4. Sim et al.[13] Chronic
inflammation and granuloma
14 >2.5
5. Sebro et al. [14] Tuberculosis and
coccidioidmycosis 6 >2.5
6 Wang et al. [22] Tuberculosis 15 >2.5
7 Li et al. [10] Granulomatous
inflammation 31 >2.5
DISCUSSION OF THE RESULTS
Malignant nodules can progress and spread quickly, a highly sensitive test to diagnose it early is of critical importance to avoid fatal outcomes. Also, benign nodules are prevalent, their identification is critical to avoid invasive biopsy procedures that put patients at risk of infection and bleeding, and it could reduce costs of unnecessary procedures, hence a highly specific test that could identify benign lesions is as essential [3]. The review of 18F-FDG-PET/CT in the diagnosis of SPNs of 20 studies for 2441 nodules had a sensitivity ranging from 64% to 100% and a specificity of 29% to 96%. Since of its higher acceptable overall sensitivity, 18F-FDG-PET/CT can be used by physicians when ruling out malignancy. A negative result of 18F-FDG-PET/CT diagnosing malignancy in a suspected patient, can rule out malignancy, and avoid the necessity to perform invasive biopsy procedures on benign nodules. However, a positive 18F-FDG-PET/CT can not prove malignancy, and a biopsy procedure is needed to prove its true nature [5]. The specificity of 18F-FDG-PET/CT is intermediate, and its value does not encourage its use for ruling in malignancy in a suspected nodule. 18F-FDG-PET/CT is able to identify a substantial amount of true positive and true negative patients; however, it does result in false-positive and false-negative findings [8]. Out of 125 false-positive results from seven studies, infective inflammatory diseases were the most common disorder manifesting as malignant nodules. Specifically, tuberculosis and inflammatory conditions causing granuloma formation. All false-positive lesions shared an SUVmax value > 2.5 with malignant nodules, proving the semiquantitative method of PET/CT interpretation must be interpreted with caution when tested positive for malignancy. False-positive results, if not detected, can result in unnecessary treatment, management, and procedures [3]. False-negative results might cause mortality from undiagnosed proliferating cancer. Out of the included studies, the diagnostic performance of PET/CT for the evaluation of SPN varied due to method of PET/CT interpretation, areas endemic of granulomatous diseases, such as research conducted by Li et al. [4] where PET/CT reported high false-positive 31 and false negative 43 results with a sensitivity and specificity of 80.2% and 38.% respectively.
Sensitivity and specificity are statistical measures calculated for a binary classification test to group the outcomes of the test and inform about a diagnostic performance of the test. 18F-FDG-PET/CT is the diagnostic test in question for grouping solitary pulmonary nodules into malignant and benign lesions. In a clinical setting, sensitivity and specificity value are compared to the accuracy of a "gold standard" test [25]. The best standard test considered the most reliable since it can correctly identify people who have the disease, which is known as sensitivity, and can correctly identify people who do not have the disease known as specificity. The "gold standard" of solitary pulmonary nodule diagnosis is a tissue biopsy sample that is obtained surgically or by percutaneous resection; however, these techniques are invasive and put the patient at significant risks such as pneumonia, pneumothorax, severe bleeding and wound infection [3]. Clinical application of a binary test depends on its sensitivity and specificity, a test with high sensitivity when tests negative can rule out the examined disease—a highly specific test when tests positive can rule in the tested disease [25]. Research study, sensitivity and specificity values of 18F-FDG-PET/CT varied with some studies reporting a high sensitivity and a low specificity of 18F-FDG-PET/CT, such as that conducted by Gibson et al. [15]. Other studies reported a low sensitivity and a high specificity, such as that conducted by Veronesi et al. [9]. Zhao et al. [4] reported both high sensitivity and specificity, while Evangelista et al. [11] reported lower sensitivity specificity. Studies that indicated high sensitivity suggest that 18F-FDG-PET/CT can rule out malignancy when it tests negative; however, studies with low sensitivity contradict this conclusion. Studies that show 18F-FDG-PET/CT as a highly specific indicator that when tested positive 18F-FDG-PET/CT can confirm malignancy; however, studies with low specificity contradict this recommendation. Based on sensitivity and specificity results, the value of 18F-FDG-PET/CT in SPN diagnosis is variable; however, because of its overall higher sensitivity, its diagnostic value is that it can reduce the number of biopsies on benign solitary pulmonary nodules.
Limitations of 18F-FDG-PET/CT in SPN diagnoses
A test with a sensitivity of 70% can correctly identify 70% of the people who have the disease. It can not, however, identify the remaining 30%, which will be the false-negative group. On the other hand, a test with a 70% specificity is capable of identifying 70% of the people who do not have the disease; the remaining 30% will be the false-positive group [25]. Since the results of sensitivity and specificity are not 100%, false-positive, and false-negative results are inevitable, as sensitivity increases, false-positive rates increase, causing a lower specificity, and as specificity increases, false-negative rate increase lowering sensitivity. Sensitivity contains no information on false-positive rates, so if a test that has a sensitivity of 90% is positive, that does not mean that there is a probability of 90% to have the disease since there could be false positive outcomes [25]. In included studies, Sebro et al. [14] reported 95.1% sensitivity and six false-positive results out of seventy-two nodules. Chen et al. [5] reported sensitivity 82%, specificity 65%, and 25 false-positives. Zhao et al. [8] reported sensitivity 88.7%, specificity 91%, and 29 false-positives. Opoka et al. [12] reported sensitivity 95%, specificity 88%, and 5 false-positives. Sim et al. [13] reported sensitivity 86.7%, specificity 50%, and 14 false-positives.
Causes of false-positive results
main cause of false-positive results with median SUVmax value >2.5. Sim et al. [13] reported chronic inflammation and granuloma as the main cause of false-positive results with median SUVmax value >2.5. In the research studies, the main cause of false-positive results fell into the infective and inflammatory group of benign solitary pulmonary nodules. Also, there was an overlap in the metabolic uptake of infective/inflammatory conditions and malignant nodules with no significant difference between their average SUVmax values.
Qualitative and semiquantitative assessment of SPN
interpretation by semiquantitative and qualitative analysis methods. The American College of chest physicians, recommends chest computed tomography scans every (3, 6, 12, and 24 months) to monitor a benign diagnosis of negative PET/CT scans for solid nodules ≥ 8mm with 5-65% of malignancy and biopsy intervention for malignancy confirmation of positive PET/CT scans [26].
Enhancement of PET/CT performance
Dual-time point imagine (DTPI) versus single-time point imaging (STPI)
A proposed method of PET/CT evaluation enhancement is by incorporating dual time point imaging versus single time point imaging the difference between the two is that dual time imaging adds an imaging scan at a late stage after FDG injection. In contrast, in single time point imaging, only one image is obtained after a specified time of FDG injection. In order to obtain a better glucose metabolic tissue activity, SUVmax measured once tissue uptake of FDG reaches its maximal point. Images obtained after 1 hour of FDG injection do not display full absorption of FDG by tissues; this could limit the semiquantitative value of SUVmax, and lead to false-negative results [3]. The change of SUVmax between the initial image and later image differentiates between benign and malignant nodules. In a study reported by Chen et al. [13], an increase of >10% of SUVmax value between the first scan at 60 minutes and second scan at 180 minutes after FDG injection was a criterion for malignancy. Based on this criterion, the study reported a sensitivity of 82% and specificity of 48% compared to STPI visual interpretation based on the degree and distribution of FDG uptake by the lesion. The sensitivity and specificity of which were 83% and 65%, respectively. The study concluded that DTPI PET/CT was not beneficial in differentiating benign from malignant nodules.
CONCLUSIONS
REFERENCES
1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246:697–722.
2. Dabrowska M, Kolasa A, Zukowska M, Lesiński J, Domagała-Kulawik J, Maskey-Warzechowska M, et al. [Analysis of solitary pulmonary nodules found in chest radiograms]. Pneumonol Alergol Pol. 2009;77:37–42.
3. Sim YT, Poon FW. Imaging of solitary pulmonary nodule—a clinical review. Quant Imaging Med Surg. 2013;3:316–26.
4. Zhao L, Tong L, Lin J, Tang K, Zheng S, Li W, et al. Characterization of solitary pulmonary nodules with 18F-FDG PET/CT relative activity distribution analysis. Eur Radiol. 2015;25:1837–44. 5. Chen S, Li X, Chen M, Yin Y, Li N, Li Y. Limited diagnostic value of Dual-Time-Point (18)F-FDG PET/CT imaging for classifying solitary pulmonary nodules in granuloma-endemic regions both at visual and quantitative analyses. Eur J Radiol. 2016;85:1744–9.
6. Ambrosini V, Nicolini S, Caroli P, Nanni C, Massaro A, Marzola MC, et al. PET/CT imaging in different types of lung cancer: An overview. European Journal of Radiology. 2012;81:988–1001. 7. Garcia-Velloso MJ, Bastarrika G, de-Torres JP, Lozano MD, Sanchez-Salcedo P, Sancho L, et al. Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT. Lung Cancer. 2016;97:81–6.
8. Zhao M, Chang B, Wei Z, Yu H, Tian R, Yuan L, et al. The role of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT. World J Surg Oncol. 2015;13:271. 9. Veronesi G, Travaini LL, Maisonneuve P, Rampinelli C, Bertolotti R, Spaggiari L, et al. Positron emission tomography in the diagnostic work-up of screening-detected lung nodules. Eur Respir J. 2015;45:501–10.
10. Li S, Zhao B, Wang X, Yu J, Yan S, Lv C, et al. Overestimated value of (18)F-FDG PET/CT to diagnose pulmonary nodules: Analysis of 298 patients. Clin Radiol. 2014;69:352-357.
11. Evangelista L, Panunzio A, Polverosi R, Pomerri F, Rubello D. Indeterminate lung nodules in cancer patients: pretest probability of malignancy and the role of 18F-FDG PET/CT. AJR Am J Roentgenol. 2014;202:507–14.
13. Sim YT, Goh YG, Dempsey MF, Han S, Poon FW. PET-CT evaluation of solitary pulmonary nodules: correlation with maximum standardized uptake value and pathology. Lung. 2013;191:625–32.
14. Sebro R, Aparici CM, Hernandez-Pampaloni M. FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease. Ann Nucl Med. 2013;27:400–5.
15. Gibson G, Kumar AR, Steinke K, Bashirzadeh F, Roach R, Windsor M, et al. Risk stratification in the investigation of pulmonary nodules in a high-risk cohort: positron emission tomography/computed tomography outperforms clinical risk prediction algorithms. Internal Medicine Journal. 2017;47:1385–92.
16. Perandini S, Soardi GA, Larici AR, del Ciello A, Rizzardi G, Solazzo A, et al. Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation. Eur Radiol. 2017;27:2042–6.
17. van Gómez López O, García Vicente AM, Honguero Martínez AF, Jiménez Londoño GA, Vega Caicedo CH, León Atance P, et al. (18)F-FDG-PET/CT in the assessment of pulmonary solitary nodules: comparison of different analysis methods and risk variables in the prediction of malignancy. Transl Lung Cancer Res. 2015;4:228–35.
18. Demir Y, Polack BD, Karaman C, Ozdoğan O, Sürücü E, Ayhan S, et al. The diagnostic role of dual-phase (18)F-FDG PET/CT in the characterization of solitary pulmonary nodules. Nucl Med Commun. 2014;35:260–7.
19. Dabrowska M, Krenke R, Korczynski P, Maskey-Warzechowska M, Zukowska M, Kunikowska J, et al. Diagnostic accuracy of contrast-enhanced computed tomography and positron emission tomography with 18-FDG in identifying malignant solitary pulmonary nodules. Medicine (Baltimore). 2015;94:e666.
20. Ohno Y, Nishio M, Koyama H, Seki S, Tsubakimoto M, Fujisawa Y, et al. Solitary pulmonary nodules: Comparison of dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic first-pass contrast-enhanced MR imaging, and FDG PET/CT. Radiology. 2015;274:563–75.
21. Ren Y-Y, Li Y-C, Wu H-B, Wang Q-S, Han Y-J, Zhou W-L, et al. [Combined use of thin-section CT and 18F-FDG PET/CT for characterization of solitary pulmonary nodules]. Nan Fang Yi Ke Da Xue Xue Bao. 2017;37:283–9.
23. Şahin E, Kara A, Elboğa U. Contribution of nonattenuation-corrected images on FDG-PET/CT in the assessment of solitary pulmonary nodules. Radiol Med. 2016;121:944–9.
24. Lin K-H, Lee R-C, Liu R-S, Chang C-Y. The prognostic value of tumor shadow disappearance rate on integrated PET/CT evaluation of solitary pulmonary nodules with low glucose metabolism. Nucl Med Commun. 2016;37:356–62.
25. Parikh R, Mathai A, Parikh S, Chandra Sekhar G, Thomas R. Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol. 2008;56:45–50.
