title: Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region.
abstract: OBJECTIVE
  To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated.
  
  
  METHODS
  One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate <25% of the preradiotherapy flow rate.
  
  
  RESULTS
  The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%-40% to 90-100% in patients with a mean parotid dose of 35-45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%-100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD(50) (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve (m = 0.45 at 1 year postradiotherapy).
  
  
  CONCLUSIONS
  This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).
authors.affiliation: Department of Radiotherapy, University Hospital Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands. JR@radcl.ruu.nl
authors.forename: J M
authors.initials: JM
authors.lastname: Roesink
authors.forename: M A
authors.initials: MA
authors.lastname: Moerland
authors.forename: J J
authors.initials: JJ
authors.lastname: Battermann
authors.forename: G J
authors.initials: GJ
authors.lastname: Hordijk
authors.forename: C H
authors.initials: CH
authors.lastname: Terhaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000378:metabolism / Q000528:radiation effects*; D011336:Probability; D011446:Prospective Studies; D011836:Radiation Tolerance; D011880:Radiotherapy Planning, Computer-Assisted; D012463:Saliva / Q000378:metabolism*; D014057:Tomography, X-Ray Computed