title: Regional radiation dose susceptibility within the parotid gland: effects on salivary loss and recovery.
abstract: OBJECTIVE
  Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study.
  
  
  METHODS
  Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman's rank correlation coefficients, local linear regression) and parametric (least-sum of squares, least-median of squares) techniques.
  
  
  RESULTS
  Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (DL,  45 Gy) + min (DR,  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A3m = 0.0604 Gy(-1) and A1y = 0.0379 Gy(-1). Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose-response dimorphism were observed.
  
  
  CONCLUSIONS
  Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a population's mean recovery will exceed 20%-30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Haley
authors.initials: H
authors.lastname: Clark
authors.affiliation: Oral Oncology/Dentistry, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Hovan
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California-San Diego, La Jolla, California 92093.
authors.forename: Vitali
authors.initials: V
authors.lastname: Moiseenko
authors.affiliation: Department of Medical Physics, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada.
authors.forename: Jonn
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reinsberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D010306:Parotid Gland / Q000503:physiopathology / Q000528:radiation effects*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D020127:Recovery of Function; D012463:Saliva / Q000378:metabolism; D014987:Xerostomia / Q000209:etiology* / Q000503:physiopathology; D055815:Young Adult