title: Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma.
abstract: OBJECTIVE
  When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma.
  
  
  METHODS
  132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasm), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival.
  
  
  RESULTS
  Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P = 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD.
  
  
  CONCLUSIONS
  This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: A
authors.initials: A
authors.lastname: Terahara
authors.forename: A
authors.initials: A
authors.lastname: Niemierko
authors.forename: M
authors.initials: M
authors.lastname: Goitein
authors.forename: D
authors.initials: D
authors.lastname: Finkelstein
authors.forename: E
authors.initials: E
authors.lastname: Hug
authors.forename: N
authors.initials: N
authors.lastname: Liebsch
authors.forename: D
authors.initials: D
authors.lastname: O'Farrell
authors.forename: S
authors.initials: S
authors.lastname: Lyons
authors.forename: J
authors.initials: J
authors.lastname: Munzenrider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002817:Chordoma / Q000532:radiotherapy*; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017785:Photons / Q000627:therapeutic use; D016016:Proportional Hazards Models; D061766:Proton Therapy; D011879:Radiotherapy Dosage; D012737:Sex Factors; D019292:Skull Base Neoplasms / Q000532:radiotherapy*; D011522:Protons
chemical_list: D011522:Protons