title: Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study.
abstract: BACKGROUND
  The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.
  
  
  METHODS
  Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, gamma-glutamyl transpeptidase, 8-isoprostagladin F2alpha and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.
  
  
  RESULTS
  Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.
  
  
  CONCLUSIONS
  Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0316 Oslo, Norway. a.k.sakhi@medisin.uio.no
authors.forename: Amrit K
authors.initials: AK
authors.lastname: Sakhi
authors.forename: Kjell M
authors.initials: KM
authors.lastname: Russnes
authors.forename: Magne
authors.initials: M
authors.lastname: Thoresen
authors.forename: Nasser E
authors.initials: NE
authors.lastname: Bastani
authors.forename: Anette
authors.initials: A
authors.lastname: Karlsen
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Smeland
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000532:radiotherapy*; D002338:Carotenoids / Q000032:analysis / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D011379:Prognosis; D011446:Prospective Studies; D020266:Radiotherapy, Conformal; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002338:Carotenoids