Diagnostic models for fever of unknown origin based on 18F-FDG PET/CT: a prospective study in China

Jia Chen, MingYou Xing, Dong Xu, NaNa Xie, WenCong Zhang, QiuRong Ruan, JianXin Song, Jia Chen, MingYou Xing, Dong Xu, NaNa Xie, WenCong Zhang, QiuRong Ruan, JianXin Song

Abstract

Background: This study aims to analyze the 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) characteristics of different causes of fever of unknown origin (FUO) and identify independent predictors to develop a suitable diagnostic model for distinguishing between these causes. A total of 524 patients with classical FUO who underwent standard diagnostic procedures and PET/CT were prospectively studied. The diagnostic performance of PET/CT imaging was analyzed, and relevant clinical parameters that could improve diagnostic efficacy were identified. The model was established using the data of 369 patients and the other 155 patients comprised the validation cohort for verifying the diagnostic performance of the model.

Results: The metabolic characteristics of the "hottest" lesion, the spleen, bone marrow, and lymph nodes varied for various causes. PET/CT combined with clinical parameters achieved better discrimination in the differential diagnosis of FUO. The etiological diagnostic models included the following factors: multisite metabolic characteristics, blood cell counts, inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and lactate dehydrogenase), immunological indicators (interferon gamma release assay, antinuclear antibody, and anti-neutrophil cytoplasm antibody), specific signs (weight loss, rash, and splenomegaly), and age. In the testing cohort, the AUCs of the infection prediction model, the malignancy diagnostic model, and the noninfectious inflammatory disease prediction model were 0.89 (95% CI 0.86-0.92), 0.94 (95% CI 0.92-0.97), and 0.95 (95% CI 0.93-0.97), respectively. The corresponding AUCs for the validation cohort were 0.88 (95% CI 0.82-0.93), 0.93 (95% CI 0.89-0.98), and 0.95 (95% CI 0.92-0.99), respectively.

Conclusions: 18F-FDG PET/CT has a certain level of sensitivity and accuracy in diagnosing FUO, which can be further improved by combining it with clinical parameters. Diagnostic models based on PET/CT show excellent performance and can be used as reliable tools to discriminate the cause of FUO. Trial registration This study (a two-step method apparently improved the physicians' level of diagnosis decision-making for adult patients with FUO) was registered on the website http://www.clinical-trials.gov on January 14, 2014, with registration number NCT02035670.

Keywords: 18F-FDG PET/CT; Clinical parameters; Diagnostic model; FUO.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
a ROC curve of SUVmax and the maximum SUVmax of the spleen, bone marrow, and lymph node in diagnosing infection. b ROC curve of SUVmax and the maximum SUVmax of the spleen, bone marrow, and lymph node in diagnosing malignancy. c ROC curve of SUVmax and the maximum SUVmax of the spleen, bone marrow, and lymph node in diagnosing NIID
Fig. 2
Fig. 2
a ROC curve of the infection prediction model. b ROC curve of the malignancy prediction model. c ROC curve of the NIID prediction model
Fig. 3
Fig. 3
a ROC curve of the infection model in the validation cohort. b ROC curve of the malignancy model in the validation cohort. c ROC curve of the NIID model in the validation cohort

References

    1. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine. 1961;40:1–30. doi: 10.1097/00005792-196102000-00001.
    1. Petersdorf RG. Fever of unknown origin. An old friend revisited. Arch Intern Med. 1992;152(1):21–22. doi: 10.1001/archinte.1992.00400130047001.
    1. Durack DT, Street AC. Fever of unknown origin—reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35–51.
    1. Wright WF, Auwaerter PG. Fever and fever of unknown origin: review, recent advances, and lingering dogma. Open Forum Infect Dis. 2020;7(5):ofaa132. doi: 10.1093/ofid/ofaa132.
    1. Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015;128(10):1138.e1–1138.e15. doi: 10.1016/j.amjmed.2015.06.001.
    1. Haidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022;386(5):463–477. doi: 10.1056/NEJMra2111003.
    1. Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med. 2003;253(3):263–275. doi: 10.1046/j.1365-2796.2003.01120.x.
    1. Yan YJ, Chen CY, Liu YY, et al. Application of machine learning for the prediction of etiological types of classic fever of unknown origin. Front Public Health. 2021;9:800549. doi: 10.3389/fpubh.2021.800549.
    1. Xu T, Wang L, Wu S, et al. Utility of a simple scoring system in differentiating bacterial infections in cases of fever of unknown origin. Clin Infect Dis. 2020;71(Suppl 4):S409–S415. doi: 10.1093/cid/ciaa1520.
    1. Efstathiou SP, Pefanis AV, Tsiakou AG, et al. Fever of unknown origin: discrimination between infectious and non-infectious causes. Eur J Intern Med. 2010;21(2):137–143. doi: 10.1016/j.ejim.2009.11.006.
    1. Letertre S, Fesler P, Zerkowski L, et al. Place of the 18F-FDG-PET/CT in the diagnostic workup in patients with classical fever of unknown origin (FUO) J Clin Med. 2021;10(17):3831. doi: 10.3390/jcm10173831.
    1. Ergül N, Halac M, Cermik TF, et al. The diagnostic role of FDG PET/CT in patients with fever of unknown origin. Mol Imaging Radionucl Ther. 2011;20(1):19–25. doi: 10.4274/MIRT.20.04.
    1. Tokmak H, Ergonul O, Demirkol O, Cetiner M, Ferhanoglu B. Diagnostic contribution of (18)F-FDG-PET/CT in fever of unknown origin. Int J Infect Dis. 2014;19:53–58. doi: 10.1016/j.ijid.2013.10.009.
    1. Wang Q, Li YM, Li Y, et al. 18F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study. Eur J Nucl Med Mol Imaging. 2019;46(1):159–65. doi: 10.1007/s00259-018-4121-1.
    1. Wang WX, Cheng ZT, Zhu JL, et al. Combined clinical parameters improve the diagnostic efficacy of 18F-FDG PET/CT in patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO): a prospective study in China. Int J Infect Dis. 2020;93:77–83. doi: 10.1016/j.ijid.2020.01.030.
    1. Hung BT, Wang PW, Su YJ, et al. The efficacy of 18F-FDG PET/CT and 67Ga SPECT/CT in diagnosing fever of unknown origin. Int J Infect Dis. 2017;62:10–17. doi: 10.1016/j.ijid.2017.06.019.
    1. Gafter-Gvili A, Raibman S, Grossman A, et al. [18F] FDG-PET/CT for the diagnosis of patients with fever of unknown origin. Q J Med. 2015;108(4):289–298. doi: 10.1093/qjmed/hcu193.
    1. Schönau V, Vogel K, Englbrecht M, et al. The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study. Ann Rheum Dis. 2018;77(1):70–77. doi: 10.1136/annrheumdis-2017-211687.
    1. Georga S, Exadaktylou P, Petrou I, et al. Diagnostic value of 18F-FDG-PET/CT in patients with FUO. J Clin Med. 2020;9(7):2112. doi: 10.3390/jcm9072112.
    1. Bleeker-Rovers CP, Vos FJ, Mudde AH, et al. A prospective multicenter study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin. Eur J Nucl Med Mol Imaging. 2007;34(5):694–703. doi: 10.1007/s00259-006-0295-z.
    1. Pereira AM, Husmann L, Sah BR, et al. Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin. Nucl Med Commun. 2016;37(1):57–65. doi: 10.1097/MNM.0000000000000395.
    1. Jamar F, Buscombe J, Chiti A, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54(4):647–658. doi: 10.2967/jnumed.112.112524.
    1. Hess S, Hansson SH, Pedersen KT, et al. FDG-PET/CT in infectious and inflammatory diseases. PET Clin. 2014;9(4):497–519. doi: 10.1016/j.cpet.2014.07.002.
    1. Vaidyanathan S, Patel CN, Scarsbrook AF, et al. FDG PET/CT in infection and inflammation—current and emerging clinical applications. Clin Radiol. 2015;70(7):787–800. doi: 10.1016/j.crad.2015.03.010.
    1. Kouijzer IJE, Mulders-Manders CM, Bleeker-Rovers CP, et al. Fever of unknown origin: the value of FDG-PET/CT. Semin Nucl Med. 2018;48(2):100–107. doi: 10.1053/j.semnuclmed.2017.11.004.
    1. Besson FL, Chaumet-Riffaud P, Playe M, et al. Contribution of 18F-FDG PET in the diagnostic assessment of fever of unknown origin (FUO): a stratification-based meta-analysis. Eur J Nucl Med Mol Imaging. 2016;43(10):1887–1895. doi: 10.1007/s00259-016-3377-6.
    1. Sioka C, Assimakopoulos A, Fotopoulos A. The diagnostic role of (18)F fluorodeoxyglucose positron emission tomography in patients with fever of unknown origin. Eur J Clin Invest. 2015;45(6):601–608. doi: 10.1111/eci.12439.
    1. Takeuchi M, Dahabreh IJ, Nihashi T, et al. Nuclear imaging for classic fever of unknown origin: meta-analysis. J Nucl Med. 2016;57(12):1913–1919. doi: 10.2967/jnumed.116.174391.
    1. Wright WF, Auwaerter PG, Dibble EH, et al. Imaging a fever-redefining the role of 2-deoxy-2-[18F] fluoro-D-glucose-positron emission tomography/computed tomography in fever of unknown origin investigations. Clin Infect Dis. 2021;72(7):1279–1286. doi: 10.1093/cid/ciaa1220.
    1. Wu ZH, Xing MY, Wei S, et al. Establishment of a predictive model related to pathogen invasion for infectious diseases and its diagnostic value in fever of unknown origin. Curr Med Sci. 2018;38(6):1025–1031. doi: 10.1007/s11596-018-1979-x.
    1. Chinese Society of Nuclear Medicine (2014) Basic requirements of clinical quality control and quality assurance on SPECT(/CT) and PET/ CT (2014 edition). Chin J Nucl Med Mol Imaging. 2014;8(6):343–448. (Chinese)
    1. Hu TD, Wang SP, Huang L, et al. A clinical-radiomics nomogram for the preoperative prediction of lung metastasis in colorectal cancer patients with indeterminate pulmonary nodules. Eur Radiol. 2019;29(1):439–449. doi: 10.1007/s00330-018-5539-3.
    1. Chen XF, Tang YY, Mo YK, et al. A diagnostic model for coronavirus disease 2019(COVID-19) based on radiological semantic and clinical features: a multi-center study. Eur Radiol. 2020;30(9):4893–4902. doi: 10.1007/s00330-020-06829-2.
    1. Zhou GY, Zhou Y, Zhong CJ, et al. Retrospective analysis of 1,641 cases of classic fever of unknown origin. Ann Transl Med. 2020;8(11):690. doi: 10.21037/atm-20-3875.
    1. Zhao MZ, Ruan QR, Xing MY, et al. A diagnostic tool for identification of etiologies of fever of unknown origin in adult patients. Curr Med Sci. 2019;39(4):589–596. doi: 10.1007/s11596-019-2078-3.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere