Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases

Background and purpose: Acute radiotherapy reactions are commonly underestimated and under-reported in the literature. Our aim was to evaluate the incidence and risk factors for acute reactions during postoperative radiotherapy in endometrial cancer patients. Material and methods: Performed was detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. Two hundred forty seven patients (78%) received both intracavitary (BRT) and external beam irradiation (EBRT), 49 patients (15%) received only BRT and 21 patients (7%) - only EBRT. BRT included radium (Ra) or cesium (Cs). The mean total dose at 0.5 cm for Ra and Cs was 50.5±10.3 Gy and 48.4±15.0 Gy, respectively, and the mean dose rate - 0.47±0.06 Gy/h and 1.42±0.41 Gy/h, respectively. Mean EBRT dose in the ICRU reference point was 49.0±3.7 Gy given in fractions of 1.54-2.49 Gy (mean 2.0±0.17 Gy). Radiotherapy and Oncology Group classification system was employed to score acute reactions. The impact of patient- and treatment-related factors on the risk of acute bowel and urinary bladder reactions was assessed with uni- and multivariate tests. Results: Acute radiotherapy reactions of any grade occurred in 265 patients (84%) including bowel complications in 66% and urinary bladder complications in 36%. There were 21 severe (grade 3 or 4) reactions, all but one seen in the patients treated with combined EBRT and BRT. Higher total dose (P=0.024), higher EBRT dose (P=0.022) and higher age (P=0.026) were correlated with increased acute bowel toxicity in univariate analysis. Multivariate analysis showed that higher EBRT dose (P=0.015) and older age (P=0.016) were independently correlated with the risk of acute bowel events. Higher total dose (P=0.009), BRT dose (P=0.029), BRT dose rate (P=0.004), EBRT fraction size (P=0.007), the use of Cs BRT (P=0.001) and lower parity (P=0.041) were correlated with increased risk of acute bladder toxicity in univariate test. Multivariate analysis demonstrated that the independent risk factors for acute bladder events were BRT dose rate (P=0.002) and low parity (P=0.042) and there was a trend for EBRT dose (P=0.076). In multivariate analysis there was no impact of other clinical factors (FIGO stage, diabetes mellitus, hypertension, prior abdominal surgery) on the risk of acute bowel and/or bladder reactions nor was the impact of surgery-to-radiotherapy interval, overall radiotherapy time and overall treatment time. Conclusions: The risk of acute reactions depends both on treatment-related (BRT dose rate, EBRT dose) and patient-related factors (age, parity). Precise treatment prescription, planning and verification are of paramount concern. Further studies are warranted to evaluate the impact of extrinsic and intrinsic factors associated with acute normal tissue injury