title: Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer.
abstract: OBJECTIVE
  In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients.
  
  
  METHODS
  Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram <-950, RA950) were measured. Patients were classified into three subgroups based on qualitative and quantitative COPD and tumour-specific imaging phenotypes: (1) tumour-specific ventilation defects (TSD), (2) tumour-specific and other ventilation defects without emphysema (TSDV), and, (3) tumour-specific and other ventilation defects with emphysema (TSDVE).
  
  
  RESULTS
  Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = .02) and FEV1/FVC (p = .04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA950, p < .001). There were significant relationships for whole-lung VDP (p < .05), but not RECIST or tumour-lobe VDP measurements with pulmonary function and exercise measurements. Preliminary analysis for non-tumour burden ventilation abnormalities using Reader-operator-characteristic (ROC) curves reflected a 94% classification rate for smoking pack-years, 93% for FEV1/FVC and 82% for RA950. ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV1/FVC (0.92/0.80/4.6/0.3), RA950 (0.92/0.80/4.6/0.3) and RECIST (0.58/0.80/2.9/1.1).
  
  
  CONCLUSIONS
  In this prospectively planned interim-analysis of a larger clinical trial, NSCLC patients were classified based on COPD imaging phenotypes. A proof-of-concept evaluation showed that FEV1/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy.
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, London, Canada; Department of Medical Biophysics, The University of Western Ontario, London, Canada.
authors.forename: Khadija
authors.initials: K
authors.lastname: Sheikh
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, London, Canada; Department of Medical Biophysics, The University of Western Ontario, London, Canada.
authors.forename: Dante P I
authors.initials: DP
authors.lastname: Capaldi
authors.affiliation: Department of Oncology, The University of Western Ontario, London, Canada.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hoover
authors.affiliation: Department of Oncology, The University of Western Ontario, London, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.affiliation: Department of Oncology, The University of Western Ontario, London, Canada.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Yaremko
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, London, Canada; Department of Medical Biophysics, The University of Western Ontario, London, Canada; Department of Oncology, The University of Western Ontario, London, Canada.
authors.forename: Grace
authors.initials: G
authors.lastname: Parraga
keywords: COPD; Cancer; Functional magnetic resonance imaging; Lung; Phenotype; Radiotherapy