Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling

Fiona J Gilbert, Scott Harris, Kenneth A Miles, Jonathan R Weir-McCall, Nagmi R Qureshi, Robert C Rintoul, Sabina Dizdarevic, Lucy Pike, Donald Sinclair, Andrew Shah, Rosemary Eaton, Andrew Clegg, Valerio Benedetto, James E Hill, Andrew Cook, Dimitrios Tzelis, Luke Vale, Lucy Brindle, Jackie Madden, Kelly Cozens, Louisa A Little, Kathrin Eichhorst, Patricia Moate, Chris McClement, Charles Peebles, Anindo Banerjee, Sai Han, Fat Wui Poon, Ashley M Groves, Lutfi Kurban, Anthony J Frew, Matthew E Callister, Philip Crosbie, Fergus V Gleeson, Kavitasagary Karunasaagarar, Osei Kankam, Steve George, Fiona J Gilbert, Scott Harris, Kenneth A Miles, Jonathan R Weir-McCall, Nagmi R Qureshi, Robert C Rintoul, Sabina Dizdarevic, Lucy Pike, Donald Sinclair, Andrew Shah, Rosemary Eaton, Andrew Clegg, Valerio Benedetto, James E Hill, Andrew Cook, Dimitrios Tzelis, Luke Vale, Lucy Brindle, Jackie Madden, Kelly Cozens, Louisa A Little, Kathrin Eichhorst, Patricia Moate, Chris McClement, Charles Peebles, Anindo Banerjee, Sai Han, Fat Wui Poon, Ashley M Groves, Lutfi Kurban, Anthony J Frew, Matthew E Callister, Philip Crosbie, Fergus V Gleeson, Kavitasagary Karunasaagarar, Osei Kankam, Steve George

Abstract

Background: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach.

Objectives: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies.

Design: Multicentre comparative accuracy trial.

Setting: Secondary or tertiary outpatient settings at 16 hospitals in the UK.

Participants: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included.

Interventions: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up.

Main outcome measures: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography.

Results: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51).

Limitations: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening.

Conclusions: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider.

Future work: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol.

Study registration: This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 17. See the NIHR Journals Library website for further project information.

Keywords: COST-EFFECTIVENESS; DCE-CT; DIAGNOSTIC ACCURACY TRIAL; DIAGNOSTIC IMAGING; LUNG CANCER; PET/CT; SOLITARY PULMONARY NODULE (SPN).

References

    1. Gilbert FJ, Harris S, Miles KA, Weir-McCall JR, Qureshi NR, Campbell Rintoul R, et al. Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules [published online ahead of print December 9 2021]. Thorax 2021.
    1. Cancer Research UK. Lung Cancer Incidence Statistics. URL: (accessed 25 September 2018).
    1. Tanner NT, Dai L, Bade BC, Gebregziabher M, Silvestri GA. Assessing the generalizability of the National Lung Screening Trial: comparison of patients with stage 1 disease. Am J Respir Crit Care Med 2017;196:602–8.
    1. Barnett PG, Ananth L, Gould MK, Veterans Affairs Positron Emission Tomography Imaging in the Management of Patients with Solitary Pulmonary Nodules (VA SNAP) Cooperative Study Group. Cost and outcomes of patients with solitary pulmonary nodules managed with PET scans. Chest 2010;137:53–9.
    1. NHS. NHS to Rollout Lung Cancer Scanning Trucks Across the Country. URL: (accessed 4 May 2019).
    1. Black C, Bagust A, Boland A, Walker S, McLeod C, De Verteuil R, et al. The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews. Health Technol Assess 2006;10(3).
    1. UK National Screening Committee. UK NSC Recommendation on Lung Cancer Screening. (accessed 31 December 2020).
    1. Callister ME, Baldwin DR, Akram AR, Barnard S, Cane P, Draffan J, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax 2015;70(Suppl. 2):ii1–ii54.
    1. 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;284:228–43.
    1. 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.
    1. National Institute for Health and Care Excellence (NICE). Lung Cancer: Diagnosis and Management. NICE guideline [NG122]. London: NICE; 2019.
    1. Li ZZ, Huang YL, Song HJ, Wang YJ, Huang Y. The value of 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules: a meta-analysis. Medicine 2018;97:e0130.
    1. Sim YT, Poon FW. Imaging of solitary pulmonary nodule – a clinical review. Quant Imaging Med Surg 2013;3:316–26.
    1. Cronin P, Dwamena BA, Kelly AM, Carlos RC. Solitary pulmonary nodules: meta-analytic comparison of cross-sectional imaging modalities for diagnosis of malignancy. Radiology 2008;246:772–82.
    1. Swensen SJ, Viggiano RW, Midthun DE, Müller NL, Sherrick A, Yamashita K, et al. Lung nodule enhancement at CT: multicenter study. Radiology 2000;214:73–80.
    1. Field JK, Duffy SW, Baldwin DR, Whynes DK, Devaraj A, Brain KE, et al. UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 2016;71:161–70.
    1. 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.
    1. Christensen JA, Nathan MA, Mullan BP, Hartman TE, Swensen SJ, Lowe VJ. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol 2006;187:1361–7.
    1. Herder GJ, Van Tinteren H, Comans EF, Hoekstra OS, Teule GJ, Postmus PE, et al. Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer. Thorax 2003;58:47–51.
    1. Gould MK, Sanders GD, Barnett PG, Rydzak CE, Maclean CC, McClellan MB, Owens DK. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724–35.
    1. Keith CJ, Miles KA, Griffiths MR, Wong D, Pitman AG, Hicks RJ. Solitary pulmonary nodules: accuracy and cost-effectiveness of sodium iodide FDG-PET using Australian data. Eur J Nucl Med Mol Imaging 2002;29:1016–23.
    1. Gambhir SS, Shepherd JE, Shah BD, Hart E, Hoh CK, Valk PE, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol 1998;16:2113–25.
    1. Shigeru K, Kiyoshi I, Masumi W, Hideo K, Shoichi K. Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[18F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small-cell lung carcinoma) in Japan. Chest 2000;117:346–53.
    1. Dietlein M, Weber K, Gandjour A, Moka D, Theissen P, Lauterbach KW, Schicha H. Cost-effectiveness of FDG-PET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany. Eur J Nucl Med 2000;27:1441–56.
    1. Gugiatti A, Grimaldi A, Rossetti C, Lucignani G, De Marchis D, Borgonovi E, Fazio F. Economic analyses on the use of positron emission tomography for the work-up of solitary pulmonary nodules and for staging patients with non-small-cell-lung-cancer in Italy. Q J Nucl Med Mol Imaging 2004;48:49–61.
    1. Comber LA, Keith CJ, Griffiths M, Miles KA. Solitary pulmonary nodules: impact of quantitative contrast-enhanced CT on the cost-effectiveness of FDG-PET. Clin Radiol 2003;58:706–11.
    1. Tsushima Y, Endo K. Analysis models to assess cost effectiveness of the four strategies for the work-up of solitary pulmonary nodules. Med Sci Monit 2004;10:MT65–MT72.
    1. Lejeune C, Al Zahouri K, Woronoff-Lemsi MC, Arveux P, Bernard A, Binquet C, Guillemin F. Use of a decision analysis model to assess the medicoeconomic implications of FDG PET imaging in diagnosing a solitary pulmonary nodule. Eur J Health Econ 2005;6:203–14.
    1. Pauls S, Buck AK, Halter G, Mottaghy FM, Muche R, Bluemel C, et al. Performance of integrated FDG-PET/CT for differentiating benign and malignant lung lesions – results from a large prospective clinical trial. Mol Imaging Biol 2008;10:121–8.
    1. Chang CY, Tzao C, Lee SC, Cheng CY, Liu CH, Huang WS, et al. Incremental value of integrated FDG-PET/CT in evaluating indeterminate solitary pulmonary nodule for malignancy. Mol Imaging Biol 2010;12:204–9.
    1. Bisdas S, Spicer K, Rumboldt Z. Whole-tumor perfusion CT parameters and glucose metabolism measurements in head and neck squamous cell carcinomas: a pilot study using combined positron-emission tomography/CT imaging. AJNR Am J Neuroradiol 2008;29:1376–81.
    1. Orlacchio A, Schillaci O, Antonelli L, D’Urso S, Sergiacomi G, Nicolì P, Simonetti G. Solitary pulmonary nodules: morphological and metabolic characterisation by FDG-PET-MDCT. Radiol Med 2007;112:157–73.
    1. 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.
    1. Ohno Y, Koyama H, Takenaka D, Nogami M, Maniwa Y, Nishimura Y, et al. Dynamic MRI, dynamic multidetector-row computed tomography (MDCT), and coregistered 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/CT: comparative study of capability for management of pulmonary nodules. J Magn Reson Imaging 2008;27:1284–95.
    1. Dabrowska M, Zukowska M, Krenke R, Domagała-Kulawik J, Maskey-Warzechowska M, Bogdan J, et al. Simplified method of dynamic contrast-enhanced computed tomography in the evaluation of indeterminate pulmonary nodules. Respiration 2010;79:91–6.
    1. Ohno Y, Koyama H, Matsumoto K, Onishi Y, Takenaka D, Fujisawa Y, et al. Differentiation of malignant and benign pulmonary nodules with quantitative first-pass 320-detector row perfusion CT versus FDG PET/CT. Radiology 2011;258:599–609.
    1. Ohno Y, Nishio M, Koyama H, Fujisawa Y, Yoshikawa T, Matsumoto S, Sugimura K. Comparison of quantitatively analyzed dynamic area-detector CT using various mathematic methods with FDG PET/CT in management of solitary pulmonary nodules. AJR Am J Roentgenol 2013;200:W593–602.
    1. Marom E, Bruzzi J, Truong M. Extrathoracic PET/CT findings in thoracic malignancies. J Thorac Imaging 2006;21:154–66.
    1. Qureshi NR, Rintoul RC, Miles KA, George S, Harris S, Madden J, et al. Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study. BMJ Open Respir Res 2016;3:e000156.
    1. National Institute for Health and Care Excellence. Guide to the Methods of Technology Appraisal 2013. URL: (accessed 25 September 2018).
    1. Gohagan JK, Marcus PM, Fagerstrom RM, Pinsky PF, Kramer BS, Prorok PC, et al. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9–15.
    1. Blanchon T, Bréchot JM, Grenier PA, Ferretti GR, Lemarié E, Milleron B, et al. Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR). Lung Cancer 2007;58:50–8.
    1. Alonzo TA, Pepe MS, Moskowitz CS. Sample size calculations for comparative studies of medical tests for detecting presence of disease. Stat Med 2002;21:835–53.
    1. Barrington SF, MacKewn JE, Schleyer P, Marsden PK, Mikhaeel NG, Qian W, et al. Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma. Ann Oncol 2011;22:739–45.
    1. Qureshi NR, Shah A, Eaton RJ, Miles K, Gilbert FJ, Sputnik investigators. Dynamic contrast enhanced CT in nodule characterization: how we review and report. Cancer Imaging 2016;16:16.
    1. McInnes MDF, Moher D, Thombs BD, McGrath TA, Bossuyt PM, Clifford T, et al. Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: the PRISMA-DTA statement. JAMA 2018;319:388–96.
    1. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529–36.
    1. Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw 2015;67:48.
    1. Harbord RM, Egger M, Sterne JAC. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 2006;25:3443–57.
    1. Basso Dias A, Zanon M, Altmayer S, Sartori Pacini G, Henz Concatto N, Watte G, et al. Fluorine 18-FDG PET/CT and diffusion-weighted MRI for malignant versus benign pulmonary lesions: a meta-analysis. Radiology 2019;290:525–34.
    1. Ducharme J, Goertzen AL, Patterson J, Demeter S. Practical aspects of 18F-FDG PET when receiving 18F-FDG from a distant supplier. J Nucl Med Technol 2009;37:164–9.
    1. Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programmes. 4th edn. Oxford: Oxford University Press; 2015.
    1. Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al. Review of guidelines for good practice in decision-analytic modelling in health technology assessment. Health Technol Assess 2004;8(36).
    1. Higgins JPT, Green S. Crochane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Updated March 2011. London: The Cochrance Collaboration; 2011.
    1. Deppen SA, Davis WT, Green EA, Rickman O, Aldrich MC, Fletcher S, et al. Cost-effectiveness of initial diagnostic strategies for pulmonary nodules presenting to thoracic surgeons. Ann Thorac Surg 2014;98:1214–22.
    1. Reitsma JB, Rutjes AWS, Whiting P, Vlassov VV, Leeflang MMG, Deeks JJ. Chapter 9: Assessing Methodological Quality. In Deeks JJ, Bossuyt PM, Gatsonis C, editors. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Version 1.0.0. London: The Cochrane Collaboration, 2009. URL: (accessed 25 September 2018).
    1. Cummings S, Lillington G, Richard R. Managing solitary pulmonary nodules. Am Rev Respir Dis 1986;134:453–60.
    1. Steele JD, Buell P. Asymptomatic solitary pulmonary nodules. Host survival, tumor size, and growth rate. J Thorac Cardiovasc Surg 1973;65:140–51.
    1. Beck JR, Kassirer JP, Pauker SG. A convenient approximation of life expectancy (the ‘DEALE’). I. Validation of the method. Am J Med 1982;73:883–8.
    1. Beck JR, Pauker SG, Gottlieb JE, Klein K, Kassirer JP. A convenient approximation of life expectancy (the ‘DEALE’). II. Use in medical decision-making. Am J Med 1982;73:889–97.
    1. Ohno Y, Hatabu H, Takenaka D, Higashino T, Watanabe H, Ohbayashi C, Sugimara K. CT-guided transthoracic needle aspiration biopsy of small (≤ 20 mm) solitary pulmonary nodules. Am J Roentgenol 2003;180:1665–9.
    1. Doubilet P, Begg CB, Weinstein MC, Braun P, McNeil BJ. Probabilistic sensitivity analysis using Monte Carlo Simulation. A practical approach. Med Decis Making 1985;5:157–77.
    1. Anderson R. Systematic reviews of economic evaluations: utility or futility? Health Econ 2010;19:350–64.
    1. Kielhorn A, Graf von der Schulenburg JM. The Health Economics Handbook. Auckland: Adis International Ltd; 2000.
    1. Department of Health and Social Care. NHS Reference Costs 2017/18. URL: (accessed 25 September 2018).
    1. Han Y, Kim HJ, Kong KA, Kim SJ, Lee SH, Ryu YJ, et al. Diagnosis of small pulmonary lesions by transbronchial lung biopsy with radial endobronchial ultrasound and virtual bronchoscopic navigation versus CT-guided transthoracic needle biopsy: a systematic review and meta-analysis. PLOS One 2018;13:e0191590.
    1. Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med 2011;155:137–44.
    1. Zhao J, Yorke ED, Li L, Kavanagh BD, Li XA, Das S, et al. Simple factors associated with radiation-induced lung toxicity after stereotactic body radiation therapy of the thorax: a pooled analysis of 88 studies. Int J Radiat Oncol Biol Phys 2016;95:1357–66.
    1. National Institute for Health and Care Excellence (NICE) Guideline Updates Team. Lung Cancer Update: Evidence Reviews for the Clinical and Cost Effectiveness of Different Radiotherapy Regimens with Curative Intent for NSCLC. NICE Guideline NG122: Evidence Reviews. London: NICE; 2019.
    1. London Cancer Alliance. LCA Acute Oncology Clinical Guidelines. London: London Cancer Alliance; 2014.
    1. Joint Formulary Committee. British National Formulary (online). London: BMJ Group and Pharmaceutical Press. URL: (accessed 15 July 2019).
    1. Paix A, Noel G, Falcoz PE, Levy P. Cost-effectiveness analysis of stereotactic body radiotherapy and surgery for medically operable early stage non small cell lung cancer. Radiother Oncol 2018;128:534–40.
    1. Echevarria C, Gray J, Hartley T, Steer J, Miller J, Simpson AJ, et al. Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation. Thorax 2018;73:713–22.
    1. Curtis L, Burns A. Unit Costs of Health and Social Care 2018. Canterbury: Personal Social Services Research Unit, University of Kent; 2018.
    1. Accordino MK, Wright JD, Buono D, Neugut AI, Hershman DL. Trends in use and safety of image-guided transthoracic needle biopsies in patients with cancer. J Oncol Pract 2015;11:e351–9.
    1. Ben-Aharon O, Magnezi R, Leshno M, Goldstein DA. Median survival or mean survival: which measure is the most appropriate for patients, physicians, and policymakers? Oncologist 2019;24:1469–78.
    1. Office for National Statistics. National Life Tables. Newport: Office for National Statistics; 2018.
    1. Khakwani A, et al. P2.16-21 Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage 1 non-small cell lung cancer in England. J Thorac Oncol 2018;13:S839.
    1. Rosen JE, Keshava HB, Yao X, Kim AW, Detterbeck FC, Boffa DJ. The natural history of operable non-small cell lung cancer in the National Cancer Database. Ann Thorac Surg 2016;101:1850–5.
    1. Kind P, Hardman G, Macran S. UK Population Norms for EQ-5D. Centre for Health Economics discussion paper 172. York: Centre for Health Economics, University of York; 1999.
    1. Doyle S, Lloyd A, Walker M. Health state utility scores in advanced non-small cell lung cancer. Lung Cancer 2008;62:374–80.
    1. Brindle L, Dowswell G, James EP, Clifford S, Ocansey L, Hamilton W, Banerjee A. Using a Participant-completed Questionnaire to Identify Symptoms that Predict Chest and Respiratory Disease (IPCARD): A Feasibility Study. 2015. URL: (accessed 25 September 2018).
    1. Brindle L, Pope C, Corner J, Leydon G, Banerjee A. Eliciting symptoms interpreted as normal by patients with early-stage lung cancer: could GP elicitation of normalised symptoms reduce delay in diagnosis? Cross-sectional interview study. BMJ Open 2012;2:e001977.
    1. Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J 2009;34:380–6.
    1. Hamilton W, Peters TJ, Round A, Sharp D. What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study. Thorax 2005;60:1059–65.
    1. Cassidy A, Myles JP, van Tongeren M, Page RD, Liloglou T, Duffy SW, Field JK. The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer 2008;98:270–6.
    1. Hamilton W. The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients. Br J Cancer 2009;101(Suppl. 2):80–6.
    1. Kadota K, Colovos C, Suzuki K, Rizk NP, Dunphy MP, Zabor EC, 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;19:3598–605.
    1. Lee KS, Yi C, Jeong SY, Jeong YJ, Kim S, Chung MJ, et al. Solid or partly solid solitary pulmonary nodules: their characterization using contrast wash-in and morphologic features at helical CT. Chest 2007;131:1516–25.
    1. Swensen SJ, Morin RL, Schueler BA, Brown LR, Cortese DA, Pairolero PC, Brutinel WM. Solitary pulmonary nodule: CT evaluation of enhancement with iodinated contrast material – a preliminary report. Radiology 1992;182:343–7.
    1. The National Lung Screening Trial Research, Team. Results of initial low-dose computed tomographic screening for lung cancer. New Engl J Med 2013;368:1980–91.
    1. 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.
    1. Leeflang MMG, Rutjes AWS, Reitsma JB, Hooft L, Bossuyt PMM. Variation of a test’s sensitivity and specificity with disease prevalence. Can Med Assoc J 2013;185:E537–44.
    1. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409.
    1. Goodman A. NELSON Trial: ‘Call to Action’ for Lung Cancer CT Scanning of High-risk Individuals. The ASCO Post; 2018. URL: (accessed 4 May 2019).
    1. National Lung Screening Trial Research Team. Lung cancer incidence and mortality with extended follow-up in the National Lung Screening Trial. J Thorac Oncol 2019;14:1732–42.
    1. De Koning H, Van Der Aalst C, Ten Haaf K, Oudkerk M. PL02.05 Effects of volume CT lung cancer screening: mortality results of the NELSON randomised-controlled population based trial. J Thorac Oncol 2018;13:S185.
    1. Crosbie PA, Balata H, Evison M, Atack M, Bayliss-Brideaux V, Colligan D, et al. Implementing lung cancer screening: baseline results from a community-based ‘Lung Health Check’ pilot in deprived areas of Manchester. Thorax 2019;74:405–9.
    1. Swensen SJ, Brown LR, Colby TV, Weaver AL. Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material. Radiology 1995;194:393–8.
    1. Yamashita K, Matsunobe S, Tsuda T, Nemoto T, Matsumoto K, Miki H, Konishi J. Solitary pulmonary nodule: preliminary study of evaluation with incremental dynamic CT. Radiology 1995;194:399–405.
    1. Swensen SJ, Brown LR, Colby TV, Weaver AL, Midthun DE. Lung nodule enhancement at CT: prospective findings. Radiology 1996;201:447–55.
    1. Potente G, Iacari V, Caimi M. The challenge of solitary pulmonary nodules: HRCT evaluation. Comput Med Imaging Graph 1997;21:39–46.
    1. Zhang M, Kono M. Solitary pulmonary nodules: evaluation of blood flow patterns with dynamic CT. Radiology 1997;205:471–8.
    1. Kim JH, Kim HJ, Lee KH, Kim KH, Lee HL. Solitary pulmonary nodules: a comparative study evaluated with contrast-enhanced dynamic MR imaging and CT. J Comput Assist Tomogr 2004;28:766–75.
    1. Choi EJ, Jin GY, Han YM, Lee YS, Kweon KS. Solitary pulmonary nodule on helical dynamic CT scans: analysis of the enhancement patterns using a computer-aided diagnosis (CAD) system. Korean J Radiol 2008;9:401–8.
    1. Bayraktaroglu S, Savaş R, Basoglu OK, Cakan A, Mogulkoc N, Cagirici U, Alper H. Dynamic computed tomography in solitary pulmonary nodules. J Comput Assist Tomogr 2008;32:222–7.
    1. Bai RJ, Cheng XG, Qu H, Shen BZ, Han MJ, Wu ZH. Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density. Chin Med J 2009;122:541–7.
    1. Jiang NC, Han P, Zhou CK, Zheng JL, Shi HS, Xiao J. Dynamic enhancement patterns of solitary pulmonary nodules at multi-detector row CT and correlation with vascular endothelial growth factor and microvessel density. Ai Zheng 2009;28:164–9.
    1. Li Y, Yang ZG, Chen TW, Yu JQ, Sun JY, Chen HJ. First-pass perfusion imaging of solitary pulmonary nodules with 64-detector row CT: comparison of perfusion parameters of malignant and benign lesions. Br J Radiol 2010;83:785–90.
    1. Shu SJ, Liu BL, Jiang HJ. Optimization of the scanning technique and diagnosis of pulmonary nodules with first-pass 64-detector-row perfusion VCT. Clin Imaging 2013;37:256–64.
    1. Ribeiro SM, Ruiz RL, Yoo HH, Cataneo DC, Cataneo AJ. Proposal to utilize simplified Swensen protocol in diagnosis of isolated pulmonary nodule. Acta Radiol 2013;54:757–64.
    1. Ye XD, Ye JD, Yuan Z, Li WT, Xiao XS. Dynamic CT of solitary pulmonary nodules: comparison of contrast medium distribution characteristic of malignant and benign lesions. Clin Transl Oncol 2014;16:49–56.
    1. Baldwin DR, Eaton T, Kolbe J, Christmas T, Milne D, Mercer J, et al. Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions? Thorax 2002;57:817–22.
    1. Gupta S, Krishnamurthy S, Broemeling LD, Morello FA Jr, Wallace MJ, Ahrar K, et al. Small (≤ 2-cm) subpleural pulmonary lesions: short-versus long-needle-path CT-guided biopsy–comparison of diagnostic yields and complications. Radiol 2005;234:631–7.
    1. Hayashi N, Sakai T, Kitagawa M, Kimoto T, Inagaki R, Ishii Y, Noriki S, Imamura Y. CT-guided biopsy of pulmonary nodules less than 3 cm: usefulness of the spring-operated core biopsy needle and frozen-section pathologic diagnosis. AJR Am J Roentgenol 1998;170:329–31.
    1. Jin KN, Park CM, Goo JM, Lee HJ, Lee Y, Kim JI, et al. Initial experience of percutaneous transthoracic needle biopsy of lung nodules using C-arm cone-beam CT systems. Eur Radiol 2010;20:2108–15.
    1. Ohno Y, Hatabu H, Takenaka D, Imai M, Ohbatashi C, Sugimura K. Transthoracic CT-guided biopsy with multiplanar reconstruction image improves diagnostic accuracy of solitary pulmonary nodules. Eur J Radiol 2004;51:160–8.
    1. Romano M, Griffo S, Gentile M, Mainenti PP, Tamburrini O, Iaccarino V, et al. CT guided percutaneous fine needle biopsy of small lung lesions in outpatients. Safety and efficacy of the procedure compared to inpatients. Radiol Med 2004;108:275–82.
    1. Santambrogio L, Nosotti M, Bellaviti N, Pavoni G, Radice F, Caputo V. CT-guided fine-needle aspiration cytology of solitary pulmonary nodules: a prospective, randomized study of immediate cytologic evaluation. Chest 1997;112:423–5.
    1. Tsukada H, Satou T, Iwashima A, Souma T. Diagnostic accuracy of CT-guided automated needle biopsy of lung nodules. AJR Am J Roentgenol 2000;175:239–43.
    1. Wagnetz U, Menezes RJ, Boerner S, Paul NS, Wagnetz D, Keshavjee S, et al. CT screening for lung cancer: implication of lung biopsy recommendations. AJR Am J Roentgenol 2012;198:351–8.
    1. Westcott JL, Rao N, Colley DP. Transthoracic needle biopsy of small pulmonary nodules. Radiol 1997;202:97–103.
    1. Wang W, Yu L, Wang Y, Zhang Q, Chi C, Zhan P, Xu C. Radial EBUS versus CT-guided needle biopsy for evaluation of solitary pulmonary nodules. Oncotarget 2018;9:15122–31.
    1. Xu C, Yuan Q, Chi C, Zhang Q, Wang Y, Wang W, et al. Computed tomography-guided percutaneous transthoracic needle biopsy for solitary pulmonary nodules in diameter less than 20 mm. Medicine 2018;97:e0154.
    1. Liu M, Huang J, Xu Y, He X, Li L, Lü Y, et al. MR-guided percutaneous biopsy of solitary pulmonary lesions using a 1.0-T open high-field MRI scanner with respiratory gating. Eur Radiol 2017;27:1459–66.
    1. Liu S, Li C, Yu X, Liu M, Fan T, Chen D, et al. Diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy of solitary pulmonary nodules. Cardiovasc Intervent Radiol 2015;38:416–21.
    1. Sa YJ, Kim JJ, Kim YD, Sim SB, Moon SW. A new protocol for concomitant needle aspiration biopsy and localization of solitary pulmonary nodules. J Cardiothorac Surg 2015;10:104.
    1. Yang W, Sun W, Li Q, Yao Y, Lv T, Zeng J, et al. Diagnostic accuracy of CT-guided transthoracic needle biopsy for solitary pulmonary nodules. PLOS ONE 2015;10:e0131373.
    1. Lee KJ, Han YM, Jin GY, Song JS. Predicting factors for conversion from fluoroscopy guided percutaneous transthoracic needle biopsy to cone-beam CT guided percutaneous transthoracic needle biopsy. J Korean Soc Radiol 2015;73:216–24.
    1. Kaaki S, KIdane B, Srinathan S, Tan L, Buduhan G. Is tissue still the issue? Lobectomy for suspicious lung nodules without confirmation of malignancy. J Surgi Oncol 2018;117:977–84.
    1. Lu R, Mei J, Zhao D, Jiang Z, Xiao H, Wang M, Ma N. Concomitant thoracoscopic surgery for solitary pulmonary nodule and atrial fibrillation. Interact Cardiovasc Thorac Surg 2018;26:402–6.
    1. Yang SM, Wang ML, Hung MH, Hsu HH, Cheng YJ, Chen JS. Tubeless uniportal thoracoscopic wedge resection for peripheral lung nodules. Ann Thorac Surg 2017;103:462–8.
    1. Li S, Jiang L, Ang KL, Chen H, Dong Q, Yang H, et al. New tubeless video-assisted thoracoscopic surgery for small pulmonary nodules. Eur J Cardiothorac Surg 2017;51:689–93.
    1. Qi H, Wan C, Zhang L, Wang J, Song Z, Zhang R, et al. Early effective treatment of small pulmonary nodules with video-assisted thoracoscopic surgery combined with CT-guided dual-barbed hookwire localization. Oncotarget 2017;8:38793–801.
    1. Müller J, Putora PM, Scheider T, Zeisel C, Brutsche M, et al. Handheld Single Photon Emission Computed Tomography (handheld SPECT) navigated video-assisted thoracoscopic surgery of computer tomography-guided radioactively marked pulmonary lesions. Interact Cardiovasc Thorac Surg 2016;23:345–50.
    1. Ghaly G, Kamel M, Nasar A, Paul S, Lee PC, Port JL, et al. Video-assisted thoracoscopic surgery Is a safe and effective alternative to thoracotomy for anatomical segmentectomy in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg 2016;101:465–72.
    1. Gill RR, Zheng Y, Barlow JS, Jayender J, Girard EE, Hartigan PM, et al. Image-guided video assisted thoracoscopic surgery (iVATS) – phase I–II clinical trial. J Surg Oncol 2015;112:18–25.
    1. Ren M, Meng Q, Zhou W, Kong F, Yang B, Yuan J, et al. Comparison of short-term effect of thoracoscopic segmentectomy and thoracoscopic lobectomy for the solitary pulmonary nodule and early-stage lung cancer. Onco Targets Ther 2014;7:1343–7.
    1. Cho J, Ko SJ, Kim SJ, Lee YJ, Park JS, Cho YJ, et al. Surgical resection of nodular ground-glass opacities without percutaneous needle aspiration or biopsy. BMC Cancer 2014;14:838.

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