title: Feasibility and potential utility of multicomponent exhaled breath analysis for predicting development of radiation pneumonitis after stereotactic ablative radiotherapy.
abstract: BACKGROUND
  In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors.
  
  
  METHODS
  Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters.
  
  
  RESULTS
  Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development.
  
  
  CONCLUSIONS
  The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.
authors.affiliation: Department of Radiation Oncology, Billerica, MA.
authors.forename: Jayaji M
authors.initials: JM
authors.lastname: Moré
authors.affiliation: Department of Radiation Oncology, Billerica, MA.
authors.forename: Neville C W
authors.initials: NCW
authors.lastname: Eclov
authors.affiliation: Department of Radiation Oncology, Billerica, MA.
authors.forename: Melody P
authors.initials: MP
authors.lastname: Chung
authors.affiliation: Department of Radiation Oncology, Billerica, MA.
authors.forename: Jacob F
authors.initials: JF
authors.lastname: Wynne
authors.affiliation: Center for Atmospheric and Environmental Chemistry, Aerodyne Research Inc., Billerica, MA.
authors.forename: Joanne H
authors.initials: JH
authors.lastname: Shorter
authors.affiliation: Center for Atmospheric and Environmental Chemistry, Aerodyne Research Inc., Billerica, MA.
authors.forename: David D
authors.initials: DD
authors.lastname: Nelson
authors.affiliation: Department of Radiation Oncology, Billerica, MA; School of Nursing, University of Pennsylvania, Philadelphia, PA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Hanlon
authors.affiliation: Kos Partners, Burlingame, CA.
authors.forename: Robert
authors.initials: R
authors.lastname: Burmeister
authors.affiliation: Kos Partners, Burlingame, CA.
authors.forename: Peter
authors.initials: P
authors.lastname: Banos
authors.affiliation: Department of Radiation Oncology, Billerica, MA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Maxim
authors.affiliation: Department of Radiation Oncology, Billerica, MA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA. Electronic address: BWLoo@Stanford.edu.
authors.forename: Billy W
authors.initials: BW
authors.lastname: Loo
authors.affiliation: Department of Radiation Oncology, Billerica, MA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address: diehn@Stanford.edu.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000032:analysis; D002248:Carbon Monoxide / Q000032:analysis; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009589:Nitrogen Oxides / Q000032:analysis; D009609:Nitrous Oxide / Q000032:analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000209:etiology*; D016634:Radiosurgery / Q000009:adverse effects*
chemical_list: D009589:Nitrogen Oxides; D002245:Carbon Dioxide; D002248:Carbon Monoxide; D009609:Nitrous Oxide