Determination and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy.

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D50 = 68.4 Gy, gamma = 6.55, s = 0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit = 61.0%, the area under the ROC curve = 0.84 and chi2 test = 0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.