The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography SUVMax in deciding on a computed tomography-guided lung biopsy in solid solitary pulmonary nodulesSUMMARY
OBJECTIVE: The aim of this study was to calculate a useful cut-off point of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography SUVMax value to decide on a computed tomography-guided percutaneous transthoracic needle biopsy for solitary pulmonary nodules of sizes between 11 and 20 mm.
METHODS: Between January 2015 and April 2020, patients with solitary pulmonary nodules who underwent computed tomography-guided percutaneous transthoracic needle biopsy were retrospectively reviewed, and those with solitary pulmonary nodules of 11–20 mm in diameter, who had undergone an 18F-fluorodeoxyglucose positron emission tomography/computed tomography examination before computed tomography-guided percutaneous transthoracic needle biopsy, were included in the study. A total of 76 patients who met the inclusion criteria were evaluated.
RESULTS: There was no distinguishing finding on the computed tomography examination (p>0.05). The SUVMax values of the malignant solid solitary pulmonary nodules were higher than the benign solitary pulmonary nodules (p<0.05).
CONCLUSION: The benign and malignant solid solitary pulmonary nodules between 11 and 20 mm have similar computed tomography features. 18F-fluorodeoxyglucose positron emission tomography/computed tomography is a useful imaging technique for distinguishing benign and malignant solitary pulmonary nodules. Notably, 4.85 SUVMax value can be used to decide on a computed tomography-guided percutaneous transthoracic needle biopsy procedure in solid solitary pulmonary nodules between 11 and 20 mm with excellent sensitivity and moderate specificity rates.
KEYWORDS:
Solitary pulmonary nodule; Biopsy; Needle; CT scans; Fluorodeoxyglucose F18
INTRODUCTION
A solitary pulmonary nodule (SPN) is a single, spherical, or oval-shaped radiopaque lesion smaller than 30 mm in diameter, which is completely surrounded by pulmonary parenchyma1. It was reported that changes in the diagnostic yield of computed tomography biopsy significantly altered preferences when the probability of malignancy was 10 or 30% of current smokers or ex-smokers2. The malignancy rate is approximately 30% for SPNs with a diameter of 21–30 mm and approximately 12% for those with a diameter of 11–20 mm3. The 5-year survival rate for lung cancer is approximately 15.6% since it is diagnosed in an advanced stage in most patients4. Therefore, the early diagnosis of malignant SPNs is critical to increase the survival of lung cancer patients.
CT-PTNB is a safe and effective minimally invasive procedure with high diagnostic accuracy5. Nodule size is one of the major risk factors for increased complication rates6. The smaller size of SPNs increases the failure rate of accessing the target lesion, the rate of insufficient tissue sampling, and the rate of false-negative results, and it is also linked to a higher complication rate7,8. Therefore, it may be difficult to decide on a CT-PTNB procedure due to the higher risk of complications and inadequate biopsy results, especially in SPNs under 20 mm. As an alternative to tissue sampling in managing solid SPNs larger than 8 mm, regardless of risk group, a 3-month thorax CT and/or PET/CT follow-up is recommended by the Fleischner Society guidelines9.
18F-FDG PET/CT is a metabolic imaging method routinely performed in oncology practice10. 18F-FDG PET/CT has been successfully used to investigate SPNs since 2000s11. In literature, although many publications have reported the role of 18F-FDG PET/CT, there is no consensus on the cut-off value of SUVMax in different size pulmonary nodules.
The aim of this study was to calculate a useful cut-off point of the 18F-FDG PET/CT SUVMax value to decide on a CT-PTNB for solid SPNs of sizes between 11 and 20 mm.
METHODS
This study conformed in accordance with the 2013 Declaration of Helsinki. The study was approved by the Ethics Committee of Gaziantep University (No: 2020/326). Written informed consent was obtained from all individual participants included in the study.
Patients
All biopsy procedures were decided considering the Fleischner Society 2013 and 2017 criteria9. Between January 2015 and April 2020, patients with SPNs who underwent CT-PTNB in the interventional radiology department of our hospital were retrospectively reviewed. A total of 112 patients with SPNs who had complete CT-PTNB reports were found in our interventional radiology database. In total, 36 of these patients were excluded from the study due to having SPNs larger than 20 mm in size (n=17), having subsolid nodules (n=13), or not undergoing an 18F-FDG PET/CT examination despite having SNPs of 11–20 mm in diameter (n=6). Finally, a total of 76 patients (53 males and 23 females, mean age 62.21±12.69 years), who met the inclusion criteria were evaluated.
Biopsy procedure
Biopsies were performed on patients with INR <1.5 and platelet count >50,000 K/μL. Positioning (supine, prone, or lateral) was adjusted based on SPN location for safe needle access. Using a Siemens CT (SOMATOM) with 20 mAs, 120 kV, 8×1.25 mm collimation, and 2.5 mm slice thickness, each procedure employed an 18-G cutting needle and a 17-G coaxial needle. At least three cuts were taken for adequate tissue sampling, and a post-procedural CT was conducted to check for complications such as pneumothorax or hemorrhage.
Diagnostic evaluation
CT-PTNB diagnoses were categorized as malignant, benign, unspecified (atypical cells), and non-diagnostic (insufficient tissue). Final diagnoses were confirmed via surgical resection, follow-up CT, or lab/pathology exams. A ≥20% reduction in nodule size on follow-up CT signified a benign SPN.
Computed tomography images
Diagnostic contrast-enhanced or non-contrast thorax CT images were reviewed by two radiologists, each with 5 years of experience, who were blinded to the pathologic diagnosis. The CT morphological features of the solid SPNs, nodule diameter (mm), nodule contour (smooth, lobulated, spiculated), localization, hilar lymphadenopathy (LAP), and emphysema were determined based on consensus.
18F-fluorodeoxyglucose positron emission tomography/computed tomography images
All 18F-FDG PET/CT images were routinely obtained after at least 6 h of fasting. The 18F-FDG PET/CT images from the skull base to the middle of the thigh were obtained approximately 1 h later in patients who received 18F-FDG once their serum glucose levels were <110 mg/dL. All collected data were transferred to dedicated workstations for post-processing, and the SUVMax values of the SPNs were calculated and noted separately.
Statistical analysis
Data were analyzed using SPSS 21.0 (IBM Corp., Armonk, NY, USA). Frequency distributions were provided for categorical variables, and means, standard deviations, medians, and IQRs for numerical variables. The Mann-Whitney U test, t-test, and chi-square test assessed differences between groups, while ROC analysis determined the SUVMax cut-off value. A p-value <0.05 indicated statistical significance.
RESULTS
Biopsy-based diagnosis and final diagnosis
Sufficient tissue was obtained for pathological examination in all patients except one with a 12 mm solid SPN in the right lower lobe. The coaxial CT-PTNB diagnoses were malignant (81.5%), benign (14.5%), unspecified (2.7%), and non-diagnostic (1.3%). Final diagnoses were malignant (81.5%), benign (17.2%), and missing (1.3%). Malignant diagnoses were confirmed by surgical resection, while benign findings were accepted as final (Table 1).
Coaxial computed tomography-guided percutaneous transthoracic needle biopsy and final diagnoses of the 76 solid solitary pulmonary nodules of 11–20 mm in diameter.
There was a statistically significant relationship between pathological diagnosis and gender. The malignancy rate was higher in males than in females (p=0.037). A statistically significant difference was also observed between the pathological diagnosis and the 18F-FDG PET/CT SUVMax median values. The median SUVMax value of the malignant SPNs was significantly higher than that of the benign SPNs (med-IQR 11.2–7 vs. 6.9–13.5, p=0.006). The patient age and the CT features of the SPNs (size, contour, and presence of hilar LAP and emphysema) were similar in benign and malign cases (p>0.05) (Table 2).
Comparison of the computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of the benign and malignant solid solitary pulmonary nodules.
The ROC curve analysis was performed to obtain a cut-off value for 18F-FDG PET/CT SUVMax indicating the malignancy risk of solid SPNs. According to the ROC analysis, two cut-off values were identified for SUVMax indicating malignancy risk: 7.05 and 4.85. At the cut-off value of 7.05, SUVMax had a sensitivity of 93.1% and specificity of 83.3%. At the cut-off value of 4.85, the sensitivity and specificity of SUVMax were calculated as 100 and 66.7%, respectively.
DISCUSSION
Although the diagnostic accuracy of CT-PTNB is very high in large nodules, in SPNs smaller than 20 mm, the diagnostic accuracy rates decrease, and reaching the target lesion with a needle can be challenging8,12. Another disadvantage of CT-guided biopsy in SPNs smaller than 20 mm is increased complication rates13. The likelihood of malignancy increases in large nodules, but nodule size does not exclude malignancy9. However, lipoid pneumonia, focal atelectasis, granulomatous inflammation, and progressive massive fibrosis, which are benign conditions, can also exhibit spiculated contours14. Although well-defined margins and a smooth contour may be a sign of benignity, pulmonary metastasis and 20% of primary lung malignancies have smooth contours15. Therefore, it becomes more challenging to decide on a biopsy procedure for SPNs smaller than 20 mm.
The role of 18F-FDG PET/CT is clearer in SPNs with a 20–30 mm size compared to SPNs of 11–20 mm in diameter due to the very low specificity, low spatial resolution, and partial volume effect16. Malignant nodules have higher 18F-FDG uptake values than benign nodules17,18. In other studies, the sensitivity and specificity of SUVMax ≥2.5 were reported as 77 and 85%, respectively, for>8 mm nodules, and as 95 and 46%, respectively, for those smaller than 30 mm19,20. While the efficiency of 18F-FDG PET/CT is rather limited in lung nodules with pure ground-glass opacity, the reliability of 18F-FDG PET/CT increases in nodules with a solid component larger than 5 mm21. Another factor may be related to the necrosis content of the nodule. Due to the smaller necrosis area in small nodules, the 18F-FDG uptake increases, and PET/CT gives a higher SUVMax value16. Therefore, a wide necrotic component of larger nodules may mislead the physicians based on low SUVMax values. Furthermore, this heterogeneity of lung nodules may make it difficult to determine a cut-off value for SUVMax to distinguish benign and malignant nodules at high sensitivity and specificity rates.
Chronic granulomatous inflammation may exhibit spiculated contours on CT similar to malignant SPNs, and this decreases the specificity of 18F-FDG PET/CT20,22. The sensitivity and specificity rates of 18F-FDG PET/CT decrease in pure GGNs and subsolid nodules that have a solid component smaller than 10 mm due to the low 18F-FDG uptake23. Dabrowska et al.18 investigated a cut-off value of 18F-FDG PET/CT to identify malignant SPNs in 71 patients. They determined that at a cut-off value of 2.1, SUVMax had 77% sensitivity and 92% specificity18. The SUVMax value may decrease to 1.25 in subsolid nodules, and the low SUVMax value of benign nodules creates an overlap zone for the SUVMax value in distinguishing benign and malignant SPNs16. This overlap zone reduces the specificity rates of 18F-FDG PET/CT.
The rates of major and overall complications of CT-PTNB are reported as 5.7% and 38.8%, respectively24. In addition, emphysema and needle path length are mentioned as the risk factors of pneumothorax13,25.
This study has certain limitations that should be noted. First, the small sample size of the study makes it difficult to interpret the data. Furthermore, due to the retrospective nature and single-center design of the study, the data may be subject to bias. Multicenter, prospective, randomized studies with larger samples are needed.
CONCLUSION
Solid pulmonary nodules of 11–20 mm often have similar CT features, complicating benign versus malignant differentiation. The 18F-FDG PET/CT, with an SUVMax threshold of 4.85, improves diagnostic accuracy and helps guide CT-guided biopsies. This threshold ensures high sensitivity and balanced specificity, supporting precise biopsy decisions and enhancing patient-centered care for small SPNs.
REFERENCES
-
1 He R, Ming C, Lei Y, Chen W, Ye L, Li G, et al. Preoperative pulmonary nodule localization: a comparison of hook wire and Lung-pro-guided surgical markers. Clin Respir J. 2024;18(1):e13726. https://doi.org/10.1111/crj.13726
» https://doi.org/10.1111/crj.13726 -
2 Smith Z, Barnett SA, Gorelik A, Pascoe DM, Manser RL. Strategies for the management of solitary pulmonary nodules: a survey of patient preferences. Ann Thorac Surg. 2022;113(5):1670-5. https://doi.org/10.1016/j.athoracsur.2021.04.094
» https://doi.org/10.1016/j.athoracsur.2021.04.094 -
3 Harzheim D, Eberhardt R, Hoffmann H, Herth FJ. The solitary pulmonary nodule. Respiration. 2015;90(2):160-72. https://doi.org/10.1159/000430996
» https://doi.org/10.1159/000430996 -
4 Wood DE, Eapen GA, Ettinger DS, Hou L, Jackman D, Kazerooni E, et al. Lung cancer screening. J Natl Compr Canc Netw. 2012;10(2):240-65. https://doi.org/10.6004/jnccn.2012.0022
» https://doi.org/10.6004/jnccn.2012.0022 -
5 Hong T, Ji G, Sun T, Gui X, Ma T, Zhang H. CT-guided percutaneous transthoracic needle biopsy (PTNB): a thoracic surgeon's learning curve and experience summary. Thorac Cancer. 2023;14(7):673-82. https://doi.org/10.1111/1759-7714.14793
» https://doi.org/10.1111/1759-7714.14793 -
6 Goto M, Fukumoto K, Ichikawa Y, Tsubouchi H, Uchiyama M, Mori S. Pathologically confirmed spontaneous regression of small cell lung cancer after computed tomography-guided percutaneous transthoracic needle biopsy followed by surgery. Surg Case Rep. 2023;9(1):187. https://doi.org/10.1186/s40792-023-01759-9
» https://doi.org/10.1186/s40792-023-01759-9 -
7 Mazzone PJ, Lam L. Evaluating the patient with a pulmonary nodule: a review. JAMA. 2022;327(3):264-73. https://doi.org/10.1001/jama.2021.24287
» https://doi.org/10.1001/jama.2021.24287 -
8 Tian Y, Wang C, Yue W, Lu M, Tian H. Comparison of computed tomographic imaging-guided hook wire localization and electromagnetic navigation bronchoscope localization in the resection of pulmonary nodules: a retrospective cohort study. Sci Rep. 2020;10(1):21459. https://doi.org/10.1038/s41598-020-78146-z
» https://doi.org/10.1038/s41598-020-78146-z -
9 MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the fleischner society 2017. Radiology. 2017;284(1):228-43. https://doi.org/10.1148/radiol.2017161659
» https://doi.org/10.1148/radiol.2017161659 -
10 Wei Y, Ma L, Li P, Lu J, Ren J, Yan S, et al. FAPI compared with FDG PET/CT for diagnosis of primary and metastatic lung cancer. Radiology. 2023;308(2):e222785. https://doi.org/10.1148/radiol.222785
» https://doi.org/10.1148/radiol.222785 -
11 Zaman MU, Fatima N. 18FDG PET/CT and lung cancer: beaconhouse for treating oncologists. J Coll Physicians Surg Pak. 2023;33(12):1341-3. https://doi.org/10.29271/jcpsp.2023.12.1341
» https://doi.org/10.29271/jcpsp.2023.12.1341 -
12 Huang MD, Weng HH, Hsu SL, Hsu LS, Lin WM, Chen CW, et al. Accuracy and complications of CT-guided pulmonary core biopsy in small nodules: a single-center experience. Cancer Imaging. 2019;19(1):51. https://doi.org/10.1186/s40644-019-0240-6
» https://doi.org/10.1186/s40644-019-0240-6 - 13 Li X, Jin F, Zhou T, Ru Y, Gu F, Wang L, et al. Diagnostic accuracy of CT-guided percutaneous pulmonary biopsy for distinguishing benign and malignant solitary pulmonary nodules. Altern Ther Health Med. 2023;29(8):918-23. PMID: 37773650
-
14 Wu W, Gu L, Zhang Y, Huang X, Zhou W. Pulmonary nodule clinical trial data collection and intelligent differential diagnosis for medical internet of things. Contrast Media Mol Imaging. 2022;2022:2058284. https://doi.org/10.1155/2022/2058284
» https://doi.org/10.1155/2022/2058284 -
15 Kim TJ, Kim CH, Lee HY, Chung MJ, Shin SH, Lee KJ, et al. Management of incidental pulmonary nodules: current strategies and future perspectives. Expert Rev Respir Med. 2020;14(2):173-94. https://doi.org/10.1080/17476348.2020.1697853
» https://doi.org/10.1080/17476348.2020.1697853 -
16 Tang K, Wang L, Lin J, Zheng X, Wu Y. The value of 18F-FDG PET/CT in the diagnosis of different size of solitary pulmonary nodules. Medicine (Baltimore). 2019;98(11):e14813. https://doi.org/10.1097/MD.0000000000014813
» https://doi.org/10.1097/MD.0000000000014813 -
17 Koster EJ, Engen-van Grunsven ACH, Bussink J, Frielink C, Geus-Oei LF, Kusters B, et al. [18F]FDG Uptake and expression of immunohistochemical markers related to glycolysis, hypoxia, and proliferation in indeterminate thyroid nodules. Mol Imaging Biol. 2023;25(3):483-94. https://doi.org/10.1007/s11307-022-01776-4
» https://doi.org/10.1007/s11307-022-01776-4 -
18 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(15):e666. https://doi.org/10.1097/MD.0000000000000666
» https://doi.org/10.1097/MD.0000000000000666 -
19 Evangelista L, Panunzio A, Cervino AR, Vinante L, Al-Nahhas A, Rubello D, et al. Indeterminate pulmonary nodules on CT images in breast cancer patient: the additional value of 18F-FDG PET/CT. J Med Imaging Radiat Oncol. 2012;56(4):417-24. https://doi.org/10.1111/j.1754-9485.2012.02408.x
» https://doi.org/10.1111/j.1754-9485.2012.02408.x -
20 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(4):400-5. https://doi.org/10.1007/s12149-013-0695-7
» https://doi.org/10.1007/s12149-013-0695-7 -
21 Evangelista L, Panunzio A, Scagliori E, Sartori P. Ground glass pulmonary nodules: their significance in oncology patients and the role of computer tomography and 18F-fluorodeoxyglucose positron emission tomography. Eur J Hybrid Imaging. 2018;2(1):2. https://doi.org/10.1186/s41824-017-0021-z
» https://doi.org/10.1186/s41824-017-0021-z -
22 Yan N, Sugihara F, Hayashi N, Sasaki T, Ishii Y, Hayashi H, et al. Pulmonary mediastinal actinomycosis with "pound cake sign" on magnetic resonance imaging mimicking an infiltrative malignant tumor: a case report. Radiol Case Rep. 2024;19(8):3334-8. https://doi.org/10.1016/j.radcr.2024.05.001
» https://doi.org/10.1016/j.radcr.2024.05.001 -
23 Tsunezuka Y, Shimizu Y, Tanaka N, Takayanagi T, Kawano M. Positron emission tomography in relation to Noguchi's classification for diagnosis of peripheral non-small-cell lung cancer 2 cm or less in size. World J Surg. 2007;31(2):314-7. https://doi.org/10.1007/s00268-006-0475-9
» https://doi.org/10.1007/s00268-006-0475-9 -
24 Heerink WJ, Bock GH, Jonge GJ, Groen HJ, Vliegenthart R, Oudkerk M. Complication rates of CT-guided transthoracic lung biopsy: meta-analysis. Eur Radiol. 2017;27(1):138-48. https://doi.org/10.1007/s00330-016-4357-8
» https://doi.org/10.1007/s00330-016-4357-8 -
25 Shin B, Kim SB, Kim CW, Park IH, Lee WY, Byun CS. Risk factors related to the recurrence of pneumothorax in patients with emphysema. J Thorac Dis. 2020;12(10):5802-10. https://doi.org/10.21037/jtd-20-1557B
» https://doi.org/10.21037/jtd-20-1557B
Publication Dates
-
Publication in this collection
02 May 2025 -
Date of issue
2025
History
-
Received
08 July 2024 -
Accepted
08 Dec 2024
