Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial

  • Marco Spadafora
  • Leonardo Pace
  • Laura Evangelista
  • Luigi Mansi
  • Francesco Del Prete
  • Giorgio Saladini
  • Paolo Miletto
  • Stefano Fanti
  • Silvana Del Vecchio
  • Luca Guerra
  • Giovanna Pepe
  • Giuseppina Peluso
  • Emanuele Nicolai
  • Giovanni Storto
  • Marco Ferdeghini
  • Alessandro Giordano
  • Mohsen Farsad
  • Orazio Schillaci
  • Cesare Gridelli
  • Alberto Cuocolo
Original Article



Diagnosis of solitary pulmonary nodule (SPN) is an important public health issue and 18F-FDG PET/CT has proven to be more effective than CT alone. Pre-test risk stratification and clinical presentation of SPN could affect the diagnostic strategy. A relevant issue is whether thoracic segmental (s)-PET/CT could be implemented in patients with SPN. This retrospective multicenter study compared the results of FDG whole-body (wb)-PET/CT to those of s-PET/CT.


18F-FDG PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. The thoracic part of wb-PET/CT, considered s-PET/CT, was compared to wb-PET/CT. Clinical and PET/CT variables were investigated for SPN characterization as well as for identification of patients in whom s-PET/CT could be performed. Histopathology or follow-up data were used as a reference.


In the study population, 36% had malignant, 35% benign, and 29% indeterminate SPN. 18F-FDG uptake indicative of thoracic and extra-thoracic lesions was detectable in 13% and 3% of the patients. All patients with extra-thoracic metastases (n = 13) had thoracic lymph node involvement and highest 18F-FDG uptake at level of SPN (negative predictive value 100%). Compared to wb-PET/CT, s-PET/CT could save about 2/3 of 18F-FDG dose, radiation exposure or scan-time, without affecting the clinical impact of PET/CT.


Pre-test probability of malignancy can guide the diagnostic strategy of 18FDG-PET/CT in patients with SPN. In subjects with low-intermediate pretest probability s-PET/CT imaging might be planned in advance, while in those at high risk and with thoracic lymph node involvement a wb-PET/CT is necessary.


Pulmonary nodule 18F-fluorodeoxyglucose Segmental-PET/CT Extra-thoracic lesions 



We thank Christina A. Drace, Istituto Oncologico Veneto-IRCCS, Padova, Italia, for assistance in writing this manuscript.

Compliance with ethical standards

Conflict of interest


Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Callister ME, Baldwin DR, Akram AR, Barnard S, Cane P, Draffan J, et al. British Thoracic Society pulmonary nodule guideline development group; British Thoracic Society standards of care committee. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015;70(Suppl 2):ii1–ii54.Google Scholar
  2. 2.
    Goldstraw P, Crowley JJ. The International Association for the Study of Lung Cancer international staging project on lung cancer. J Thorac Oncol. 2006;1:281–6.CrossRefGoogle Scholar
  3. 3.
    Sim YT, Poon FW. Imaging of solitary pulmonary nodule-a clinical review. Quant Imaging Med Surg. 2013;3:316–26.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Huang B, Law MWM, Khong PL. Whole-body PET/CT scanning: estimation of radiation dose and cancer risk. Radiology. 2009;251:166–74.CrossRefPubMedGoogle Scholar
  5. 5.
    Brix G, Lechel U, Glatting G, Ziegler SI, Münzing W, Müller SP, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med. 2005;46:608–13.Google Scholar
  6. 6.
    Yi CA, Lee KS, Kim BT, Choi JY, Kwon OJ, Kim H, et al. Tissue characterization of solitary pulmonary nodule: comparative study between helical dynamic CT and integrated PET/CT. J Nucl Med. 2006;47:443–50.Google Scholar
  7. 7.
    Al-Ameri A, Malhotra P, Thygesen H, Plant PK, Vaidyanathan S, Karthik S, et al. Risk of malignancy in pulmonary nodules: a validation study of four prediction models. Lung Cancer. 2015;89:27–30.Google Scholar
  8. 8.
    Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013;143(5 Suppl):e93S–e120S.Google Scholar
  9. 9.
    MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner society. Radiology. 2005;237:395–400.Google Scholar
  10. 10.
    National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.Google Scholar
  11. 11.
    Tasdemir B, Urakci Z, Dostbil Z, Unal K, Simsek FS, Teke F, et al. Effectiveness of the addition of the brain region to the FDG-PET/CT imaging area in patients with suspected or diagnosed lung cancer. Radiol Med. 2016;121:218–24.Google Scholar
  12. 12.
    Sullivan R, Peppercorn J, Sikora K, Zalcberg J, Meropol NJ, Amir E, et al. Delivering affordable cancer care in high-income countries. Lancet Oncol. 2011;12:933–80.Google Scholar
  13. 13.
    Einstein AJ. Effects of radiation exposure from cardiac imaging. How good are the data? J Am Coll Cardiol. 2012;59:553–65.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    International Commission on Radiological Protection (ICRP) Strategic Plan for 2016–2020. Accessed March 1, 2017.
  15. 15.
    Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumor imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.Google Scholar
  16. 16.
    Delbeke D, Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med. 2006;47:885–95.Google Scholar
  17. 17.
    Spadafora M, Pace L, Mansi L. Segmental 18F-FDG-PET/CT in a single pulmonary nodule: a better cost/effectiveness strategy. Eur J Nucl Med Mol Imaging. 2017;44:1–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Spadafora M, Evangelista L, Gridelli C, Cuocolo A. Alternative imaging strategy of solitary pulmonary nodule by FDG PET/CT: can be imagined a tailored PET? Eur J Radiol. 2017;90:188–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Spadafora M, Pace L, Mansi L. The delicate balance between present and future. Eur J Nucl Med Mol Imaging. 2017;44:346–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Hustinx R. How to scan who: the delicate balance between selecting the patient and selecting the imaging protocol. Eur J Nucl Med Mol Imaging. 2017;44:5–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Evangelista L, Spadafora M, Pace L, Mansi L, Cuocolo A. Italian tailored assessment of lung indeterminate accidental nodule by proposing a segmental PET/computed tomography (s-PET/CT): Rationale and study design of a retrospective, multicenter trial. Curr Radiopharm 2018;11(1):46–49.Google Scholar
  22. 22.
    McWilliams A, Tammemagi MC, Mayo JR, Roberts H, Liu G, Soghrati K, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med. 2013;369:910–9.Google Scholar
  23. 23.
    ICRP. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37:1–332.Google Scholar
  24. 24.
    Horeweg N, van Rosmalen J, Heuvelmans MA, van der Aalst CM, Vliegenthart R, Scholten ET, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol. 2014;15:1332–41.Google Scholar
  25. 25.
    Kagna O, Solomonov A, Keidar Z, Bar-Shalom R, Fruchter O, Yigla M, et al. The value of FDG-PET/CT in assessing single pulmonary nodules in patients at high risk of lung cancer. J Nucl Med Mol Imaging. 2009;36:997–1004.Google Scholar
  26. 26.
    Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. International Association for the Study of Lung Cancer International Staging Committee. The IASLC Lung Cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.Google Scholar
  27. 27.
    Iskandrian AE, Dilsizian V, Garcia EV, Beanlands RS, Cerqueira M, Soman P, et al. Myocardial perfusion imaging: lessons learned and work to be done-update. J Nucl Cardiol. 2018;25:39–52.Google Scholar
  28. 28.
    Siegel JA, Pennington CW, Sacks B. Subjecting radiologic imaging to the linear no-threshold hypothesis: a non sequitur of non-trivial proportion. J Nucl Med. 2017;58:1–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Iglehart JK. Health insurers and medical-imaging policy: a work in progress. N Engl J Med. 2009;360:1030–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Patz EF Jr, Pinsky P, Gatsonis C, Sicks JD, Kramer BS, Tammemägi MC, et al. Over-diagnosis manuscript writing team over-diagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med. 2014;174:269–74.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marco Spadafora
    • 1
    • 2
  • Leonardo Pace
    • 3
  • Laura Evangelista
    • 4
  • Luigi Mansi
    • 5
  • Francesco Del Prete
    • 2
  • Giorgio Saladini
    • 4
  • Paolo Miletto
    • 2
  • Stefano Fanti
    • 6
  • Silvana Del Vecchio
    • 7
  • Luca Guerra
    • 8
  • Giovanna Pepe
    • 9
  • Giuseppina Peluso
    • 10
  • Emanuele Nicolai
    • 11
  • Giovanni Storto
    • 12
  • Marco Ferdeghini
    • 13
  • Alessandro Giordano
    • 14
  • Mohsen Farsad
    • 15
  • Orazio Schillaci
    • 16
    • 17
  • Cesare Gridelli
    • 18
  • Alberto Cuocolo
    • 7
  1. 1.Struttura Complessa di Medicina NucleareOspedale del MareNapoliItaly
  2. 2.Struttura Complessa di Medicina NucleareOspedale San Giuseppe MoscatiAvellinoItaly
  3. 3.Dipartimento di Medicina, Chirurgia e Odontoiatria “Scuola Medica Salernitana”Università degli Studi di SalernoSalernoItaly
  4. 4.SSD Medicina Nucleare e Imaging MolecolareIstituto Oncologico Veneto IOV – IRCCSPadovaItaly
  5. 5.Centro Interuniversitario di Ricerca per lo Sviluppo SostenibileNapoli-RomaItaly
  6. 6.Servizio di Medicina Nucleare, Policlinico S. Orsola MalpighiUniversità degli Studi di BolognaBolognaItaly
  7. 7.Dipartimento di Scienze Biomediche AvanzateUniversità degli Studi di Napoli Federico IINapoliItaly
  8. 8.Unità di Medicina Nucleare, Ospedale San GerardoUniversità di Milano BicoccaMonzaItaly
  9. 9.Unità di Medicina Nucleare, Cancer CenterHumanitas Research HospitalRozzanoItaly
  10. 10.Unità di Medicina Nucleare, Dipartimento delle ImmaginiMedicina Futura IOSAcerraItaly
  11. 11.Unità di Medicina Nucleare, Dipartimento delle ImmaginiSDN-IRCCSNapoliItaly
  12. 12.Unità di Medicina NucleareCentro di Riferimento Oncologico della Basilicata-IRCCSRionero in VultureItaly
  13. 13.Unità di Medicina Nucleare, Dipartimento delle ImmaginiOspedale Universitario Integrato di VeronaVeronaItaly
  14. 14.Istituto di Medicina NucleareUniversità Cattolica del Sacro CuoreRomaItaly
  15. 15.Dipartimento di Medicina NucleareOspedale di BolzanoBolzanoItaly
  16. 16.Dipartimento di Biomedicina e PrevenzioneUniversità Tor VergataRomaItaly
  17. 17.Servizio di Medicina NucleareIRCCS-NeuromedPozzilliItaly
  18. 18.Divisione di Oncologia MedicaOspedale San Giuseppe MoscatiAvellinoItaly

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