Background: Growing numbers of patients with cancer are surviving following treatment with pelvic radiotherapy. Eighty per cent will experience acute gastrointestinal (GI) toxicity during treatment and 50% will subsequently have a change in their bowel habit which will affect their quality of life. The main project in this thesis aims to determine whether delivery of a gastrointestinal bundle of care will decrease GI acute toxicity and late effects of pelvic chemoradiotherapy. Additional work in the thesis evaluated the newer technique of Volumetric Modulated Arc Therapy (VMAT) which delivers decreased dose to the organs at risk on planning scans. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects. There is no internationally accepted patient reported outcome measure to capture this toxicity data and this issue was addressed using Rasch analysis in a third project. Methods: A randomised controlled trial was performed. Patients who were scheduled to undergo potentially curative chemoradiotherapy for cervix and bladder cancers were recruited and randomised. The treatment group received dietetic input and if they developed lower GI symptoms they underwent investigations and treatment for bile acid malabsorption, small bowel bacterial overgrowth and lactose intolerance. The control group received standard care. Patients who were to undergo VMAT to treat gynaecological malignancy completed patient-reported outcomes at baseline, end of treatment and one year. The rates of patient-reported toxicity were compared with those of a historical cohort and were correlated with the volume of small bowel which was irradiated. Thirdly the technique of Rasch analysis was used to evaluate the Common Terminology Criteria for Adverse Events derived patient reported outcome to measure pelvic toxicity of gynaecological cancer treatments. Results: It was feasible and acceptable to deliver a GI care bundle to patients undergoing chemotherapy and pelvic radiotherapy. All patients' data were available for analysis for the primary outcome and 29 patients' data were available at the 1 year time point. GI toxicity at 6 weeks was predicted by the trial group, suggesting that the intervention benefited the patients in terms of GI toxicity at 6 weeks. It is not yet clear whether this benefit is maintained at the 1 year time point. The frequencies of acute and late GI toxicity reported by patients undergoing VMAT were similar to that of a historical cohort who received conformal therapy. There was not a strong association between the volume of small bowel which was irradiated and the toxicity which was reported suggesting that other factors are involved in the development of toxicity. Rasch analysis of the pelvic symptom questionnaire demonstrated the main issue to be response dependency. When this was accounted for by grouping items into sub-tests the questionnaire could be made to be unidimensional and showed high reliability in a symptomatic population. Conclusion: GI intervention holds promise as a measure to reduce the acute toxicity and late effects of pelvic radiotherapy. Although newer radiotherapy techniques appear to decrease the dose delivered to the small bowel this does not translate to a reduction in patient-reported toxicity. The measurement of toxicity is complex and patient-reported outcome measures should be developed with techniques such as Rasch analysis to ensure meaningful data is available to guide further developments to reduce GI toxicity secondary to pelvic radiotherapy.

Background: Pelvic radiotherapy is a well-established treatment for pelvic malignancies, with 30,000 patients per year in the UK receiving radical pelvic radiotherapy either alone or in combination with other oncological treatments. 80% develop acute gastrointestinal (GI) symptoms and 50% develop chronic GI symptoms and in parallel to improvements in survival, increasing numbers of patients are living to develop the long term consequences of treatment. Despite this, less than 20% of patients who develop chronic GI symptoms are ever referred to a gastroenterologist. Aims: 1. To determine the current practice of clinical oncologists and gastroenterologists with respect to management of chronic GI symptoms following pelvic radiotherapy in 2 parallel national surveys. 2. To determine whether specialist gastroenterological management of chronic GI symptoms following pelvic radiotherapy based on a structured algorithmic approach identifies GI diagnoses and improves outcomes. 3. To determine whether a GI care bundle comprising nutritional assessment and intervention and investigation of GI symptoms and subsequent treatment of diagnoses found is feasible and acceptable to patients. Findings: There is no formal robust screening for GI symptoms, low referral rates, patchy services, use of ineffective treatments and inadequate expertise. Oncologists underestimate the problem and under refer. Gastroenterologists are seeing low numbers of patients and lack expertise. Both groups state that a regional multidisciplinary service for patients with GI symptoms following pelvic radiotherapy would be desirable. Patients who develop GI symptoms following pelvic radiotherapy present with multiple symptoms (median 8) and thorough structured evaluation identified multiple potentially treatable diagnoses, with 28 patients (55%) having ≥2 causes for their GI symptoms. Half of diagnoses were unrelated to previous cancer treatment. Common diagnoses included radiation proctopathy, bile acid malabsorption, diverticulosis and colonic polyps. A clinically and statistically significant improvement in GI symptoms was found in parallel to GI intervention using inflammatory bowel disease questionnaire (IBDQ) (p=0.014), Vaizey incontinence questionnaire (VIQ) (p<0.0005) and the Common Terminology Criteria for Adverse Events (CTCAE) pelvic symptom questionnaire rectum-bowel subset (p=0.001). Initial data show that GI and nutritional intervention during pelvic chemoradiotherapy is both feasible and acceptable to patients. Conclusions: There is inadequate care and services for this patient group in the UK. GI intervention using a structured algorithmic approach is of benefit in terms of identifying potentially treatable diagnoses and improving symptoms. GI intervention during pelvic radiotherapy is feasible and acceptable to patients and ongoing work will determine the benefit of this intervention in terms of symptom control in the short and long term and cost benefit. A programme of mechanistic and clinical research is required to improve the understanding of this scenario.

An uncommon case with semi-spheric perivesical calcification after pelvic radiotherapy is reported and the possible pathogenesis of this phenomenon is discussed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.