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Improving lung cancer diagnosis by combining exhaled-breath data and clinical parameters

Sharina Kort, Marjolein Brusse-Keizer, Jan Willem Gerritsen, Hugo Schouwink, Emanuel Citgez, Frans de Jongh, Jan van der Maten, Suzy Samii, Marco van den Bogart, Job van der Palen
ERJ Open Research 2020 6: 00221-2019; DOI: 10.1183/23120541.00221-2019
Sharina Kort
1Dept of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
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  • ORCID record for Sharina Kort
  • For correspondence: s.kort@mst.nl
Marjolein Brusse-Keizer
2Medical School Twente, Medisch Spectrum Twente, Enschede, the Netherlands
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Jan Willem Gerritsen
3The eNose Company, Zutphen, the Netherlands
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Hugo Schouwink
1Dept of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
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Emanuel Citgez
1Dept of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
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Frans de Jongh
1Dept of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
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Jan van der Maten
4Dept of Pulmonary Medicine, Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands
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Suzy Samii
5Dept of Pulmonary Medicine, Deventer Ziekenhuis, Deventer, the Netherlands
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Marco van den Bogart
6Dept of Pulmonary Medicine, Bernhoven Uden, Uden, the Netherlands
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Job van der Palen
2Medical School Twente, Medisch Spectrum Twente, Enschede, the Netherlands
7Dept of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands
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Figures

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  • FIGURE 1
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    FIGURE 1

    Flow chart showing the different groups. NSCLC: non-small cell lung cancer.

  • FIGURE 2
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    FIGURE 2

    Combined receiver operating characteristic curve showing four predictive algorithms: logistic regression clinical variables, single Aeonose value, extended artificial neural network (ANN) and logistic regression including Aeonose value.

Tables

  • Figures
  • TABLE 1

    Clinical characteristics of subjects

    Confirmed NSCLCTotal control groupSuspected, proven negativeHealthy volunteerp-value
    Subjects n1381435984
    Age years67.1±9.162.1±7.065.2±8.859.8±4.3<0.001¶
    Males80 (58.0%)58 (40.6%)31 (52.5%)27 (32.1%)<0.001+
    Smoking status
     Current smokers49 (35.5%)19 (13.3%)13 (22.0%)6 (7.1%)<0.001+
     Ex-smokers82 (59.4%)76 (53.1%)32 (54.2%)44 (52.4%)
     Never-smokers7 (5.1%)48 (33.6%)14 (23.7%)34 (40.5%)
    Smoking exposure pack-years
     07 (5.1%)48 (33.6%)14 (23.7%)34 (40.5%)
     1–2030 (21.7%)53 (37.1%)18 (30.5%)35 (41.7%)<0.001+
     21–4053 (38.4%)25 (17.5%)17 (28.8%)8 (9.5%)
     >4048 (34.8%)17 (11.9%)10 (16.9%)7 (8.3%)
    COPD66 (47.8%)22 (15.4%)21 (35.6%)1 (1.2%)<0.001+
    BMI kg·m−225.6±4.625.9±4.826.9±5.925.2±3.80.104
    Type of NSCLC
     Adenocarcinoma88 (63.8%)
     Squamous cell carcinoma41 (29.7%)
     Large cell carcinoma4 (2.9%)
     NOS5 (3.6%)
    NSCLC stage#
     I25 (14.5%)
     II15 (10.8%)
     III39 (28.3%)
     IV64 (46.4%)

    Data are presented as mean±sd or n (%), unless otherwise stated. NSCLC: non-small cell lung cancer; BMI: body mass index; NOS: not otherwise specified.#: according to the seventh edition of the American Joint Committee on Cancer TNM staging system; ¶: after Games–Howell correction, there was a significant difference between healthy volunteers and confirmed NSCLC and healthy volunteers and suspected, proven negative subjects; +: after Holm–Bonferroni correction, there was a significant difference between healthy volunteers and confirmed NSCLC and suspected proven negative subjects.

    • TABLE 2

      Results of the univariate and multivariate logistic regression analyses for diagnosing lung cancer

      VariableUnivariate analysisMultivariate analysisβ#
      Sex2.01 (1.26–3.20)1.42 (0.76–2.58)0.34
      Age1.08 (1.05–1.11)1.05 (1.02–1.09)0.05
      BMI0.99 (0.94–1.04)−
      Smoking status−
       Current smoker17.49 (6.79–45.06)
       Ex-smoker7.56 (3.23–17.69)
       Never smokedRef.
      Smoking exposure pack-years
       0Ref.Ref.
       1–203.88 (1.56–9.65)3.48 (1.25–9.66)1.25
       21–4014.77 (5.89–37.04)10.20 (3.66–28.46)2.32
       >4019.36 (7.36–50.91)11.69 (4.04–33.87)2.46
      COPD4.90 (2.80–8.58)2.29 (1.18–4.43)0.83
      Diabetes mellitus0.70 (0.30–1.64)−
      Aeonose classification value [13]24.20 (9.71–60.33)12.67 (4.48–35.83)2.54

      Data are presented as odds ratio (95% confidence interval) unless otherwise stated. β: regression coefficient. BMI: body mass index; −: not added to the multivariate model. #: constant −5.54.

      • TABLE 3

        Diagnostic performance of the three investigated prediction models

        Positive/negativeOptimal cut-offSensitivitySpecificityPPVNPVAUC-ROC (95% CI)
        Clinical variables only138/1430.3293.5%50.0%64.5%88.8%0.80 (0.75–0.85)
        Aeonose result only138/143−0.3894.2%44.1%61.9%88.7%0.75 (0.69–0.81)
        Multivariate logistic regression model138/1430.2795.7%59.7%69.5%92.5%0.86 (0.81–0.90)
        Extended ANN138/143−0.6594.2%49.0%64.0%89.7%0.84 (0.79–0.89)

        PPV: positive predictive value; NPV: negative predictive value; AUC-ROC: area under the receiver operating curve; ANN: artificial neural network.

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        Improving lung cancer diagnosis by combining exhaled-breath data and clinical parameters
        Sharina Kort, Marjolein Brusse-Keizer, Jan Willem Gerritsen, Hugo Schouwink, Emanuel Citgez, Frans de Jongh, Jan van der Maten, Suzy Samii, Marco van den Bogart, Job van der Palen
        ERJ Open Research Jan 2020, 6 (1) 00221-2019; DOI: 10.1183/23120541.00221-2019

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        Improving lung cancer diagnosis by combining exhaled-breath data and clinical parameters
        Sharina Kort, Marjolein Brusse-Keizer, Jan Willem Gerritsen, Hugo Schouwink, Emanuel Citgez, Frans de Jongh, Jan van der Maten, Suzy Samii, Marco van den Bogart, Job van der Palen
        ERJ Open Research Jan 2020, 6 (1) 00221-2019; DOI: 10.1183/23120541.00221-2019
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