Determinants of Small Bowel Toxicity in Postoperative Pelvic Irradiation for Gynaecological Malignancies

Background: Patients treated with postoperative radiotherapy for endometrial and cervical carcinomas from 1981 to 2000 were retrospectively analysed in order to assess the rate of late small bowel toxicity. Patients and Methods: Eight hundred and six patients had received pelvic irradiation, with total doses of 40-55 Gy. The mean age was 57 years. Three hundred and eighteen patients had been treated for cervical and 488 for endometrial cancer; 46 had diabetes and 22 vascular diseases; 141 had a history of smoking and 367 were previously submitted to surgery for benign diseases. A CT treatment plan had been applied in 285 patients; 256 had been treated by arc moving therapy, 232 with 2 opposed beams (AP-PA) and 318 with 3 or 4 coplanar beams. Three hundred and forty-six were treated with X photons of 10 MV or more, 202 with 4-5 MV and 258 with cobalt gamma rays. Personalized blocks had been used in 389. Thirty-four women had received chemotherapy. Five hundred and eighty-four had been treated with dose fractions of 180 cGy or more and 56 had received a boost with brachytherapy or external beams. Eighty-one had needed treatment discontinuation due to acute small bowel toxicity. Results: The median follow-up was 70 months. Thirty five patients had bowel obstructions, after a median time of 31 months. The 5- and 10-year toxicity rates were 4 and 7%. Uni- and multivariate comparisons identified age, acute toxicity and dose fraction as predictors for complications. Conclusion: Postoperative pelvic irradiation with standard techniques for gynaecological carcinomas results in tolerable rates of clinically significant late bowel damage, while older patients suffering from significant acute toxicity seem to be at higher risk. Postoperative radiation therapy, alone or associated with chemotherapy (CHT), is a powerful modality for the treatment of tumours and, nowadays is widely applied in gynaecological carcinomas. Unfortunately, surgery followed by pelvic irradiation at standard doses (45-50 Gy in 25-28 daily fractions) is associated with morbid consequences, either during or after the completion of treatment, due to exposure of the small bowel. The small intestine is the most vulnerable organ in the pelvis and small bowel damage is the most important toxicity in postoperative pelvic irradiation, both as frequency and as clinical consequences. Late radiation injury to this organ, although relatively rare, is a serious side-effect entailing significant morbidity and mortality. According to the literature, the exact rate of severe late small bowel toxicity remains controversial, with a wide range (1-25%) and an accepted average of 5% (1-7). Several risk factors emerged from historical data, although a clear provisional model has not yet been defined (1, 5-14). Individual variations (previous laparotomies, vascular diseases, history of diabetes, inflammatory pelvic disease, age), surgical parameters (development of adhesions, unsuccessful reperitonealisation) and radiation-related factors (total dose, volume of bowel included, fractionation schedule, irradiation technique, association with chemotherapy) contribute to the toxicity pathway. The variety of involved primaries and treatments creates much confusion over the risk factors; the diffuse habit of accumulating small and large bowel toxicity and the use of different scoring systems add to the problem. Moreover, the analysis of radiation side- effects, in particular late effects, in published papers seems to suffer from statistical underpower and from differences in scoring systems. Bowel damage analysis usually included both small bowel and rectal toxicity, so that comparison between results is difficult. The aim of this work was to determine the frequency of severe late damage, limited to the small bowel, in a mono-institutional population of patients treated with postoperative pelvic radiotherapy after radical hysterectomy and to try to highlight patient, primary disease and treatment factors that can predispose to radiation injury.