title: Early Detection of Lung Cancer with Meso Tetra (4-Carboxyphenyl) Porphyrin-Labeled Sputum.
abstract: BACKGROUND
  Early detection of lung cancer in high-risk individuals reduces mortality. Low-dose spiral computed tomography (LDCT) is the current standard but suffers from an exceedingly high false-positive rate (>96%) leading to unnecessary and potentially dangerous procedures. We, therefore, set out to develop a simple, noninvasive, and quantitative assay to detect lung cancer.
  
  
  METHODS
  This proof-of-concept study evaluated the sensitivity/specificity of the CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphenyl) porphyrin (TCPP)-labeled lung sputum samples and subjects' baseline characteristics were assessed for their predictive power by multivariable logistic regression. A receiver operating characteristic curve was constructed to evaluate the sensitivity/specificity of the CyPath assay.
  
  
  RESULTS
  RFCs were detectable in cancer subjects more often than in high-risk ones (p = 0.015), and their characteristics differed between cohorts. Two independent predictors of cancer were the mean of RFC average fluorescence intensity/area per subject (p < 0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall accuracy of 81% in the test population; false-positive rate of 40% and negative predictive value of 83%.
  
  
  CONCLUSIONS
  The tetra (4-carboxyphenyl) porphyrin -based CyPath assay correctly classified study participants into cancer or high-risk cohorts with considerable accuracy. Optimizing sputum collection, sample reading, and refining the classifier should improve sensitivity and specificity. The CyPath assay thus has the potential to complement LDCT screening or serve as a stand-alone approach for early lung cancer detection.
authors.affiliation: Radiology Associates of Albuquerque, Albuquerque, New Mexico.
authors.forename: Lara
authors.initials: L
authors.lastname: Patriquin
authors.affiliation: Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Merrick
authors.affiliation: Waterbury Pulmonary Associates, Waterbury, Connecticut.
authors.forename: David
authors.initials: D
authors.lastname: Hill
authors.affiliation: Quintiles Consulting, Rockville, Maryland.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Holcomb
authors.affiliation: Bioinfo, Plantagenet, ON, Canada.
authors.forename: Madeleine E
authors.initials: ME
authors.lastname: Lemieux
authors.affiliation: bioAffinity Technologies, Inc., San Antonio, Texas.
authors.forename: Gordon
authors.initials: G
authors.lastname: Bennett
authors.affiliation: bioAffinity Technologies, Inc., San Antonio, Texas.
authors.forename: Bijal
authors.initials: B
authors.lastname: Karia
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center in San Antonio, San Antonio, Texas.
authors.forename: Vivienne I
authors.initials: VI
authors.lastname: Rebel
authors.affiliation: Thoracic Surgery, Meridian Cancer Care, Jersey Shore University Medical Center, Neptune, New Jersey. Electronic address: TBauer@meridianhealth.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011166:Porphyrins / Q000378:metabolism*; D013183:Sputum / Q000166:cytology / Q000378:metabolism*; D036542:Tomography, Spiral Computed / Q000379:methods*
chemical_list: D011166:Porphyrins