title: Detection of cancer through exhaled breath: a systematic review.
abstract: BACKGROUND
  Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of adherence at virtually no risk in population-based screening. In this review, we summarize the current evidence of exhaled breath analysis for cancer detection using standard analysis techniques and electronic nose.
  
  
  METHODS
  Relevant studies were identified searching Pubmed and Web of Science databases until April 30, 2015. Information on breath test performance, such as sensitivity and specificity, was extracted together with volatile compounds that were used to discriminate cancer patients from controls. Performance of different breath analysis techniques is provided for various cancers together with information on methodological issues, such as breath sampling protocol and validation of the results.
  
  
  RESULTS
  Overall, 73 studies were included, where two-thirds of the studies were conducted on lung cancer. Good discrimination usually required a combination of multiple biomarkers, and area under the receiver operating characteristic curve or accuracy reached levels of 0.9 or higher in multiple studies. In 25% of the reported studies, classification models were built and validated on the same datasets. Huge variability was seen in different aspects among the studies.
  
  
  CONCLUSIONS
  Analyses of exhaled breath yielded promising results, although standardization of breath collection, sample storage and data handling remain critical issues. In order to foster breath analysis implementation into practice, larger studies should be implemented in true screening settings, paying particular attention to standardization in breath collection, consideration of covariates, and validation in independent population samples.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Agne
authors.initials: A
authors.lastname: Krilaviciute
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jonathan Alexander
authors.initials: JA
authors.lastname: Heiss
authors.affiliation: Faculty of Medicine, University of Latvia, Digestive Diseases Center GASTRO, and Riga East University Hospital, Riga, Latvia.
authors.forename: Marcis
authors.initials: M
authors.lastname: Leja
authors.affiliation: Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Juozas
authors.initials: J
authors.lastname: Kupcinskas
authors.affiliation: Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Hossam
authors.initials: H
authors.lastname: Haick
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001944:Breath Tests / Q000379:methods*; D045853:Exhalation; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor
keywords: VOC; breath analysis; cancer detection; systematic review; volatile organic compound