title: Dietary Flaxseed in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation.
abstract: OBJECTIVE
  The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury (RILI), which may be prevented by the anti-inflammatory and anti-oxidant properties of Flaxseed (FS), impedes its maximum benefit.
  
  
  METHODS
  Patients with LA-NSCLC requiring definitive RT were randomized to one FS or control muffin daily from start to 2 weeks after RT. Blood and urine were collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane) and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dGuo). Tolerability was defined as consuming ≥ 75% of the intended muffins and no ≥ grade 3 gastrointestinal toxicities.
  
  
  RESULTS
  Fourteen patients (control,7; FS,7) were enrolled. The tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control, respectively. Mean percentages of intended number of muffins consumed were 37% versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were detectable. There was a trend towards decreased rates of pneumonitis in FS.
  
  
  CONCLUSIONS
  This is the first study to report FS bioavailability and quantify oxidative stress markers in NSCLC patients. FS in the administered muffin formulation did not meet tolerability criteria. Given the promising mechanism of FS as a radioprotectant, further investigations should focus on the optimal method for administration of FS.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Abigail T
authors.initials: AT
authors.lastname: Berman
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Turowski
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Cengel
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Farnese
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Basel-Brown
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Clementina
authors.initials: C
authors.lastname: Mesaros
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Blair
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lawson
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA.
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Rengan
keywords: 8-oxo dGuo; Esophagitis; Fibrosis; Flaxseed; Isoprostane; Lignan; Non-small cell lung cancer; Pneumonitis; RILI; Radiation; Radiation induced lung injury