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. 2018 Aug 16;5(1):e182815. doi: 10.1001/jamaoncol.2018.2815

Table. Biomarker Phase 1 Studies on Exhaled Volatile Organic Compounds in Cancer.

Study Cancer Type Patients With Cancer, No. Patient Groups Cancer Stage Analytical Platform Sensitivity, % Specificity, % AUC STARD Score
Barash et al,14 2015 Breast 80 Healthy, benign, cancer NR GC-MS 78a 61a 0.79a 17
Li et al,15 2014 Breast 22 Healthy, benign, cancer I-IV GC-MS 68.2a 91.7a 0.902b 20
Mangler et al,16 2012 Breast 10 Healthy, cancer T1-T4 GC-MS NR NR NR 12
Peng et al,17 2010 Breast 14 Healthy, cancer I-II or unknown GC-MS NR NR NR 14
Phillips et al,18 2003 Breast 51 Healthy, benign, cancer NR GC-MS 88.2a 73.8a NR 18
Phillips et al,19 2006 Breast 51 Benign, cancer NR GC-MS 93.8a 84.6a 0.9a 13
Wang et al,20 2014 Breast 39 Healthy, benign, cancer NR GC-MS NR NR NR 14
Amal et al,21 2015 Ovarian 48 Healthy, benign, cancer I-IV or unknown GC-MS NR NR NR 14
Peng et al,17 2010 Prostate 13 Healthy, cancer I-II GC-MS NR NR NR 14
Guo et al,22 2015 Thyroid 39 Healthy, benign, cancer NR GC-MS 100a 100a 1.0a 13
Gruber et al,23 2014 Head and neck 22 Healthy, benign, cancer Mixed or unknown GC-MS NR NR NR 15
Hakim et al,24 2011 Head and neck 8 Healthy, cancer Mixed GC-MS NR NR NR 12
Bouza et al,25 2017 Oral cavity 26 Healthy, cancer I-IV GC-MS NR NR NR 11
Szabó et al,26 2015 Oral cavity 14 Healthy, cancer NR Portable GC NR NR NR 11
Altomare et al,27 2013 Colorectal 37 Healthy, cancer I-IV GC-MS 86a 83a 0.852a 20
Amal et al, 282016 Colorectal 65 Healthy, cancer I-IV or unknown GC-MS NR NR NR 20
Peng et al,17 2010 Colorectal 22 Healthy, cancer I-IV GC-MS NR NR NR 14
Wang et al,29 2014 Colorectal 20 Healthy, cancer NR GC-MS NR NR NR 13
Abela et al,30 2009 Esophagogastric 20 Healthy, cancer II-IV TDLS NR NR NR 14
Kumar et al,31 2013 Esophagogastric 18 Healthy, benign, cancer NR SIFT-MS NR NR 0.91 18
Kumar et al,32 2015 Esophagogastric 81 Healthy, benign, cancer Mixed SIFT-MS 86.7a 81.2a 0.87a 22
Amal et al,33 2013 Gastric 74b Healthy, benign, cancer I-IV or unknown GC-MS NR NR NR 15
Amal et al,34 2016 Gastric 99 Healthy, benign, cancer I-IV or unknown GC-MS NR NR NR 20
Xu et al,35 2013 Gastric 37 Healthy, benign, cancer I-IV or unknown GC-MS NR NR NR 21
Qin et al,36 2010 Liver 30 Healthy, benign, cancer I-IV GC-MS 83.3a 91.7a NR 18
Garcia et al,37 2014 Laryngeal 10 Healthy, cancer T1-T3 GC-MS NR NR NR 8
Bajtarevic et al,38 2009 Lung 220/65 Healthy, cancer NR PTR-MS/GC-MSc 80d 100d NR 11
Bousamra et al,39 2014 Lung 107 Healthy, benign, cancer Mixed FT-ICR-MS 28 100 0.86 13
Buszewski et al,40 2011 Lung 115 Healthy, cancer NR GC-MS NR NR NR 12
Buszewski et al,41 2012 Lung 29 Healthy, cancer NR GC-MS NR NR NR 5
Chen et al,42 2005 Lung 5 Healthy, cancer NR SAW sensor NR NR NR 6
Corradi et al,43 2015 Lung 71 Benign, cancer I-IV GC-MS NR NR NR 22
Crohns et al,44 2009 Lung 11 Healthy, cancer I-IV GC-MS NR NR NR 15
Deng et al,45 2004 Lung 10 Healthy, cancer I GC-MS NR NR NR 7
Feinberg et al,46 2016 Lung 22 Healthy, cancer III-IV PTR-MS NR NR NR 15
Filipiak et al,47 2014 Lung 36 Healthy, cancer NR GC-MS NR NR NR 12
Fu et al,48 2014 Lung 97 Healthy, benign, cancer I-IV FT-ICR-MS 89.8e 81.3e NR 10
Fuchs et al,49 2010 Lung 12 Healthy, cancer >T3 GC-MS 75f 95.8f NR 11
Gaspar et al,50 2009 Lung 18 Healthy, cancer NR GC-MS 100g 100g NR 5
Handa et al,51 2014 Lung 50 Healthy, cancer I-IV IMS 76 100 NR 17
Kischkel et al,52 2010 Lung 31 Healthy, cancer >T2 GC-MS NR NR NR 8
Li et al,53 2015 Lung 85 Healthy, benign, cancer I-IV or unknown FT-ICR-MS and GC-MS 96h 84h 0.962i 19
Ligor et al,54 2009 Lung 65 Healthy, cancer NR GC-MS 51 100 NR 12
Ligor et al,55 2015 Lung 123 Healthy, cancer III-IV GC-MS 63.5a 72.4a 0.65a 11
Ma et al,56 2014 Lung 13 Healthy, cancer III-IV GC × GC-FID NR NR NR 13
Ma et al,57 2015 Lung 10 Healthy, cancer NR GC-MS NR NR NR 5
Peled et al,58 2012 Lung 28 Benign, cancer Mixed GC-MS NR NR NR 13
Peng et al,59 2009 Lung 40 Healthy, cancer III-IV GC-MS NR NR NR 13
Peng et al,17 2010 Lung 16 Healthy, cancer I-IV GC-MS NR NR NR 14
Phillips et al,60 2003 Lung 67 Benign, cancer Mixed GC-MS 85.1a 80.5a NR 19
Phillips et al,61 2007 Lung 193 Healthy, cancer Mixed GC-MS 84.6a 80.0a 0.88a 18
Phillips et al,62 2008 Lung 193 Healthy, cancer Mixed GC-MS 84.5 81 0.9 15
Poli et al,63 2005 Lung 36 Healthy, benign, cancer I-II GC-MS 72.2 93.6 NR 16
Poli et al,64 2010 Lung 40 Healthy, cancer I-III GC-MS 90 92.1 NR 16
Rudnicka et al,65 2011 Lung 23 Healthy, cancer NR GC-TOF/MS NR NR NR 5
Sakumura et al,66 2017 Lung 107 Healthy, cancer I-IV GC-MS 95 89 NR 7
Schallschmidt et al,67 2016 Lung 37 Healthy, cancer NR GC-MS 100j 100j NR 10
Schumer et al,68 2015 Lung 156 Healthy, benign, cancer 0-IV Silicon chip-MS 95.5k 64.4k NR 14
Schumer et al,69 2016 Lung 31 Benign, cancer I-IV Silicon chip-MS NR NR NR 13
Skeldon et al,70 2006 Lung 12 Healthy, cancer NR TDLS NR NR NR 14
Song et al,71 2010 Lung 43 Healthy, cancer I-IV GC-MS 95.3l 85.4l 0.94l 13
Ulanowska et al,72 2011 Lung 127 Healthy, cancer NR GC-MS NR NR NR 10
Wang et al,73 2012 Lung 88 Healthy, benign, cancer I-IV GC-MS 96.47a 9.747a 0.949j,m 13
Wehinger et al,74 2007 Lung 17 Healthy, cancer I-V PTR-MS 0.54n 0.99n 0.95o 17
Zou et al,75 2014 Lung 79 Healthy, benign, cancer I-IV GC-MS NR NR 1.0a,m 22
de Gennaro et al,76 2010 Mesothelioma 13 Healthy, benign, cancer NR GC-MS NR NR NR 13

Abbreviations: AUC, area under the curve; FT-ICR-MS, Fourier transform–ion cyclotron resonance–mass spectrometry; GC, gas chromatography; GC × GC-FID, comprehensive 2-dimensional gas chromatography with flame ionization detector; GC-MS, gas chromatography–mass spectrometry; GC-TOF/MS, gas chromatography time-of-flight mass spectrometry; IMS, ion mobility spectrometry; MS, mass spectrometry; NR, not reported; PTR-MS, proton transfer reaction–mass spectrometry; SAW, surface acoustic wave; SIFT-MS, selected ion flow tube mass spectrometry; STARD, Standards for Reporting of Diagnostic Accuracy Studies.

a

Data derived from a validated model (cancer vs healthy control and/or benign disease).

b

Data derived from nonvalidated model for all 4 compounds.

c

Compounds reported to have a negative alveolar gradient, suggesting that they were of exogenous origin.

d

Compound(s) not found to be significantly different between patients with cancer and controls.

e

Includes patients presented in an earlier publication by Xu et al.35

f

The cutoff for statistical significance was considered at P < .017.

g

PTR-MS, n = 220; GC-MS, n = 65.

h

Compounds detected by PTR-MS.

i

Data are based on the 21 compounds determined by GC-MS.

j

Compounds considered to be of exogenous origin.

k

Only compounds with positive alveolar gradients were reported.

l

Sensitivity and specificity determined from patients with 2 or more of the 4 volatile organic compounds considered as diagnostic for the presence of cancer.

m

For pentanal only.

n

Two volatile organic compounds that were used in the model were not reported.

o

Data are for patients with cancer vs all those without cancer.