Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

Purpose: When irradiating a tumor that abuts or displaces any normal struct ures, the dose constraints to those structures (if lower than the prescribe d dose) may cause dose inhomogeneity in the tumor volume at the tumor-criti cal 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 t he effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. Methods and Materials: 132 patients with skull base chordoma were treated w ith combined photon and proton irradiation between 1978 and 1993. This, stu dy reviews 115 patients whose dose-volume data and follow-up data are avail able. 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 ner ves and chiasm), the brain stem surface, and the brain stem center was limi ted to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evalua te several dose-volume parameters including the Equivalent Uniform Dose (EU D). We also analyzed several other patient and treatment factors in relatio n 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 signi ficant predictor for local control with the prognosis in males being signif icantly better than that in females (P = 0.004, hazard ratio = 2.3). In a C ox univariate analysis, with stratification by gender, the significant pred ictors for local control (at the probability level of 0.05) were EUD, the t arget volume, the minimum dose, and the D-5cc dose. The prescribed dose, hi stology, age, the maximum dose, the mean dose, the median dose, the D-90% d ose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the models including gender and EUD, or gender and t he target volume, or gender and the minimum target dose were significant. T he more biologically meaningful of these models is that of gender and EUD. Conclusion: This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target d ose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume. (C) 1999 Elsevier Science Inc.