title: Severe dry eye syndrome after radiotherapy for head-and-neck tumors.
abstract: OBJECTIVE
  To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy.
  
  
  METHODS
  The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise.
  
  
  RESULTS
  Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p < .0001 and p < .0001, respectively) and dose per fraction (p ≤ .0001 and p = .0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses <45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES.
  
  
  CONCLUSIONS
  With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation.
authors.affiliation: Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL 32610-0385, USA. bhandn@shands.ufl.edu
authors.forename: Niranjan
authors.initials: N
authors.lastname: Bhandare
authors.forename: Vitali
authors.initials: V
authors.lastname: Moiseenko
authors.forename: William Y
authors.initials: WY
authors.lastname: Song
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.forename: M Tariq
authors.initials: MT
authors.lastname: Bhatti
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D015352:Dry Eye Syndromes / Q000209:etiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012737:Sex Factors