Heart, Lung and Circulation

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification

Published:November 06, 2021DOI:


      Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification.


      From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results.


      Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura’s classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa’s classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005).


      In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.


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        • Ettinger D.S.
        • Wood D.E.
        • Aisner D.L.
        • Akerley W.
        • Bauman J.
        • Chirieac L.R.
        • et al.
        Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology.
        J Natl Compr Canc Netw. 2017; 15: 504-535
        • Gould M.K.
        • Donington J.
        • Lynch W.R.
        • Mazzone P.J.
        • Midthun D.E.
        • Naidich D.P.
        • 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: e93-e120S
        • Cho H.
        • Lee H.Y.
        • Kim J.
        • Kim H.K.
        • Choi J.Y.
        • Um S.W.
        • et al.
        Pure ground glass nodular adenocarcinomas: are preoperative positron emission tomography/computed tomography and brain magnetic resonance imaging useful or necessary?.
        J Thorac Cardiovasc Surg. 2015; 150: 514-520
        • Kim T.J.
        • Park C.M.
        • Goo J.M.
        • Lee K.W.
        Is there a role for FDG PET in the management of lung cancer manifesting predominantly as ground-glass opacity?.
        AJR Am J Roentgenol. 2012; 198: 83-88
        • Cheran S.K.
        • Nielsen N.D.
        • Patz J.E.F.
        False-negative findings for primary lung tumors on FDG positron emission tomography: staging and prognostic implications.
        AJR Am J Roentgenol. 2004; 182: 1129-1132
        • Nomori H.
        • Watanabe K.
        • Ohtsuka T.
        • Naruke T.
        • Suemasu K.
        • Uno K.
        Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images.
        Lung Cancer. 2004; 45: 19-27
        • Shim S.S.
        • Lee K.S.
        • Kim B.T.
        • Choi J.Y.
        • Chung M.J.
        • Lee E.J.
        Focal parenchymal lung lesions showing a potential of false-positive and false-negative interpretations on integrated PET/CT.
        AJR Am J Roentgenol. 2006; 186: 639-648
        • Iwano S.
        • Ito S.
        • Tsuchiya K.
        • Kato K.
        • Naganawa S.
        What causes false-negative PET findings for solid-type lung cancer?.
        Lung Cancer. 2013; 79: 132-136
        • Travis W.D.
        • Brambilla E.
        • Noguchi M.
        • Nicholson A.G.
        • Geisinger K.
        • Yatabe Y.
        • et al.
        International association for the study of lung cancer/American ThoracicSociety/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary.
        Proc Am Thorac Soc. 2011; 8: 381-385
        • Tabbò F.
        • Nottegar A.
        • Guerrera F.
        • Migliore E.
        • Luchini C.
        • Maletta F.
        • et al.
        Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma.
        Hum Pathol. 2018; 75: 167-178
        • Yu Y.
        • Jian H.
        • Shen L.
        • Zhu L.
        • Lu S.
        Lymph node involvement influenced by lung adenocarcinoma subtypes in tumor size ≤3 cm disease: a study of 2268 cases.
        Eur J Surg Oncol. 2016; 42: 1714-1719
        • Guerrera F.
        • Lococo F.
        • Evangelista A.
        • Rena O.
        • Ampollini L.
        • Vannucci J.
        Risk of recurrence in stage I adenocarcinoma of the lung: a multi-institutional study on synergism between type of surgery and type of nodal staging.
        J Thorac Dis. 2019; 11: 564-572
        • Baldelli E.
        • Bellezza G.
        • Haura E.B.
        • Crinó L.
        • Cress W.D.
        • Deng J.
        • et al.
        Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors.
        Oncotarget. 2015; 6: 32368-32379
        • Guerrera F.
        • Tabbò F.
        • Bessone L.
        • Maletta F.
        • Gaudiano M.
        • Ercole E.
        • et al.
        The influence of tissue ischemia time on RNA integrity and patient-derived xenografts (PDX) engraftment rate in a non-small cell lung cancer (NSCLC) Biobank.
        PLoS One. 2016; 11: e0145100
        • Lococo F.
        • Galeone C.
        • Formisano D.
        • Bellafiore S.
        • Filice A.
        • Annunziata T.
        • et al.
        18F-fluorodeoxyglucose positron emission tomographic scan in solid-type p-stage-I pulmonary adenocarcinomas: what can produce false-negative results?.
        Eur J Cardiothorac Surg. 2017; 51: 667-673
        • Nakamura H.
        • Saji H.
        • Shinmyo T.
        • Tagaya R.
        • Kurimoto N.
        • Koizumi H.
        • et al.
        Close association of IASLC/ATS/ERS lung adenocarcinoma subtypes with glucose-uptake in positron emission tomography.
        Lung Cancer. 2015; 87: 28-33
        • Yoshizawa A.
        • Motoi N.
        • Riely G.J.
        • Sima C.S.
        • Gerald W.L.
        • Kris M.G.
        Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases.
        Modern Pathol. 2011; 24: 653-664
        • Guerrera F.
        • Errico L.
        • Evangelista A.
        • Filosso P.L.
        • Ruffini E.
        • Lisi E.
        • et al.
        Exploring atage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection.
        Eur J Cardiothorac Surg. 2015; 47: 1037-1043
        • Hallett W.A.
        • Marsden P.K.
        • Cronin B.F.
        • O’Doherty M.J.
        Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer.
        Eur J Nucl Med. 2001; 28: 919-922
        • Wu H.B.
        • Wang L.
        • Wang Q.S.
        • Han Y.J.
        • Li H.S.
        • Zhou W.L.
        • et al.
        Adenocarcinoma with BAC features presented as the nonsolid nodule is prone to be false negative on 18F-FDG PET/CT.
        Biomed Res Int. 2015; 2015: 243681
        • Grogan E.L.
        • Deppen S.A.
        • Ballman K.V.
        • Andrade G.M.
        • Verdial F.C.
        • Aldrich M.C.
        • et al.
        Accuracy of fluorodeoxyglucose-positron emission tomography within the clinical practice of the American College of Surgeons Oncology Group Z4031 trial to diagnose clinical stage I non-small cell lung cancer.
        Ann Thorac Surg. 2014; 97: 1142-1148
        • Higashi K.
        • Ueda Y.
        • Seki H.
        • Yuasa K.
        • Oguchi M.
        • Noguchi T.
        • et al.
        Fluorine-18-FDG. PET imaging is negative in bronchioloalveolar lung carcinoma.
        J Nucl Med. 1998; 39: 1016-1020
        • Awab A.
        • Hamadani M.
        • Peyton M.
        • Brown B.
        False-negative PET scan with bronchioloalveolar carcinoma: an important diagnostic caveat.
        Am J Med Sci. 2007; 334: 311-313
        • Truini A.
        • Santos Pereira P.
        • Cavazza A.
        • Spagnolo P.
        • Nosseir S.
        • Longo L.
        • et al.
        Classification of different patterns of pulmonary adenocarcinomas.
        Expert Rev Respir Med. 2015; 9: 571-586
        • Penzo M.
        • Ludovini V.
        • Treré D.
        • Siggillino A.
        • Vannucci J.
        • Bellezza G.
        • et al.
        Dyskerin and TERC expression may condition survival in lung cancer patients.
        Oncotarget. 2015; 6: 21755-21760
        • Kadota K.
        • Colovos C.
        • Suzuki K.
        • Rizk N.P.
        • Dunphy M.P.
        • Zabor E.C.
        • et al.
        FDG-PET SUVmax combined with IASLC/ATS/ERS histologic classification improves the prognostic stratification of patients with stage I lung adenocarcinoma.
        Ann Surg Oncol. 2012; 19: 3598-3605