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Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma

Kumar, Sacheen MRCS; Huang, Juzheng PhD; Abbassi-Ghadi, Nima MRCS; Mackenzie, Hugh A. MRCS; Veselkov, Kirill A. PhD; Hoare, Jonathan M. PhD, FRCP; Lovat, Laurence B. PhD, FRCP; Španěl, Patrik PhD; Smith, David PhD, FRS; Hanna, George B. PhD, FRCS

doi: 10.1097/SLA.0000000000001101
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Objective: The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls.

Background: The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies.

Methods: A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs.

Results: Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs—pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal—were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ± 0.01 and 0.87 ± 0.03, respectively.

Conclusions: Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.

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*Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK

Department of Medicine, Imperial College London, St Mary's Hospital, London, UK

Department of Surgery and Interventional Science, National Medical Laser Centre, University College London, London, UK

§J. Heyrovsky Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Hartshill, UK.

Reprints: George B Hanna, PhD, FRCS, Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Wing, St Mary's Hospital, London W2 1NY, UK. E-mail: g.hanna@imperial.ac.uk.

Disclosure: Supported by the Imperial National Institute for Health Research Biomedical Research Centre, Rosetrees Trust and The Stoneygate Trust (M261CD1), and the Imperial College Junior Fellowship Research Program. The authors declare no conflicts of interest.

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