LATE COMPLICATIONS AFTER POSTOPERATIVE RADIOTHERAPY IN ENDOMETRIAL CANCER - ANALYSIS OF 317 CONSECUTIVE CASES WITH APPLICATION OF LINEAR-QUADRATIC MODEL

Purpose: To evaluate the incidence and risk factors for late complicat ions after postoperative radiotherapy in endometrial cancer patients. Methods and Material: We performed a detailed retrospective analysis o f 317 endometrial cancer patients given postoperative radiotherapy. A total of 247 patients (78%) received both intracavitary (BRT) and exte rnal beam irradiation (XRT); 49 patients (15%) received only BRT, and 21 (7%) only XRT. BRT included radium (Ra) and cesium (Cs). The mean d ose rate for both isotopes at 0.5 cm from the applicator surface was 0 .47 +/- 0.06 and 1.42 +/- 0.41 Gy/h, and the mean total dose was 50.5 +/- 10.3 and 48.4 +/- 15.0 Gy, respectively. Mean BRT dose at 0.5 cm w as 50.1 +/- 11.7 Gy (range 14.5-71.0). Mean XRT dose in the Internatio nal Commission on Radiation Units and Measurements (ICRU) reference po int was 49.0 +/- 3.7 Gy (range 22.0-66.0) given in fractions of 1.54-2 .49 Gy (mean 2.0 +/- 0.17) with a two- or four-field technique. Follow -up ranged from 4 to 21 years (median 7.3). Normalized total dose (NTD ) including XRT and BRT doses was calculated based on a linear quadrat ic equation. Results: Five-year overall survival rate was 75%, and 5-y ear disease-free survival (censored for noncancer deaths) was 81%. Lat e radiotherapy complications of any grade occurred in 158 patients (51 %), including bowel complications in 41% and urinary bladder complicat ions in 21%. A total of 37 grade 3 or 4 complications were observed in 33 patients (11%), of whom 32 were treated with both XRT and BRT. Sev ere bowel and/or urinary bladder complications occurred in 24 patients : in 14 of 72 patients (19.4%) who received XRT and Cs BRT, and in 10 of 172 patients (6.0%) applied XRT and Ra BRT. The higher proportion o f severe bowel and/or bladder complications in the former group was du e to the particularly frequent rate of these events (30.0%) in a subse t of 47 patients who received XRT combined with Cs BRT at the dose rat e of 1.7 Gy/h and the total BRT dose of 60 Gy. Higher NTD, XRT fractio n dose, BRT dose rate, Cs BRT, two-field XRT technique, short overall radiotherapy time, and older are were correlated with increased late-e vent risk in univariate analysis. Multivariate Cox analysis demonstrat ed that the independent risk factors for late bowel complications were NTD (p = 0.000) and BRT dose rate (p = 0.036), whereas for bladder co mplications they were BRT dose rate (p = 0.005) and XRT fraction dose (p = 0.041). Neither clinical factor (age, parity, prior abdominal sur gery, FIGO stage, diabetes mellitus, or hypertension) nor the surgery- to-radiotherapy interval, nor overall radiotherapy time was independen tly associated with the risk of late bladder or bowel complications. C onclusions: The risk of late complications after postoperative radioth erapy in endometrial cancer depends mainly on treatment-related factor s: NTD, BRT dose rate, and XRT fraction dose. The use of combined XRT and BRT increases the risk of late effects. NTD calculations including BRT dose rate and XRT fraction dose enable estimation of radiobiologi cally equivalent dose and can decrease the risk of mistakes when the r adiotherapy regimen is changed. (C) 1998 Elsevier Science Inc.