title: Accuracy of volatile urine biomarkers for the detection and characterization of lung cancer.
abstract: BACKGROUND
  The mixture of volatile organic compounds in the headspace gas of urine may be able to distinguish lung cancer patients from relevant control populations.
  
  
  METHODS
  Subjects with biopsy confirmed untreated lung cancer, and others at risk for developing lung cancer, provided a urine sample. A colorimetric sensor array was exposed to the headspace gas of neat and pre-treated urine samples. Random forest models were trained from the sensor output of 70% of the study subjects and were tested against the remaining 30%. Models were developed to separate cancer and cancer subgroups from control, and to characterize the cancer. An additional model was developed on the largest clinical subgroup.
  
  
  RESULTS
  90 subjects with lung cancer and 55 control subjects participated. The accuracies, reported as C-statistics, for models of cancer or cancer subgroups vs. control ranged from 0.795 - 0.917. A model of lung cancer vs. control built using only subjects from the largest available clinical subgroup (30 subjects) had a C-statistic of 0.970. Models developed and tested to characterize cancer histology, and to compare early to late stage cancer, had C-statistics of 0.849 and 0.922 respectively.
  
  
  CONCLUSIONS
  The colorimetric sensor array signature of volatile organic compounds in the urine headspace may be capable of distinguishing lung cancer patients from clinically relevant controls. The incorporation of clinical phenotypes into the development of this biomarker may optimize its accuracy.
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. mazzonp@ccf.org.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mazzone
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. wangx6@ccf.org.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Metabolomx, Mountainview, CA, USA. slim@isensesystems.com.
authors.forename: Sung
authors.initials: S
authors.lastname: Lim
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. choih@ccf.org.
authors.forename: Humberto
authors.initials: H
authors.lastname: Choi
authors.affiliation: National Jewish Health, Denver, CO, USA. JettJ@NJHealth.org.
authors.forename: James
authors.initials: J
authors.lastname: Jett
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA. avachani@mail.med.upenn.edu.
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. zhangq@ccf.org.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. beukemm@ccf.org.
authors.forename: Mary
authors.initials: M
authors.lastname: Beukemann
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Ave., A90, Cleveland, OH, 44195, USA. seeleym@ccf.org.
authors.forename: Meredith
authors.initials: M
authors.lastname: Seeley
authors.affiliation: Metabolomx, Mountainview, CA, USA. rmartino@isensesystems.com.
authors.forename: Ray
authors.initials: R
authors.lastname: Martino
authors.affiliation: Metabolomx, Mountainview, CA, USA. prhodes@isensesystems.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Rhodes
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D003124:Colorimetry / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D055549:Volatile Organic Compounds / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D055549:Volatile Organic Compounds