Kuku, SY; (2015) Radiation-Induced Bowel Injury (RIBI): Exploring potential predictive and prognostic factors and strategies to improve the management of women treated with Pelvic Radiation for Cervical and Endometrial Cancers: Cancer Survivorship: Improving Quality of Life after Treatment for Gynaecological Cancers. Doctoral thesis , UCL (University College London).

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Abstract

Introduction: The true incidence of radiation toxicity to the bowel remains unknown; in the UK, it has been reported that about 90% of patients who receive pelvic radiotherapy will have some change in their bowel function, and in up to 50% this affects their quality of life significantly (Andreyev, 2007). It is unclear why some cancer survivors develop significant symptoms that arise as a result of multiple functional, structural and physiological deficiencies related to radiation injury. Aims: There is a need to identify tissue specific biomarkers of normal tissue injury and identify those patients who might be at risk of severe injury to the bowel. In this thesis, I sought to investigate the true incidence and presentation of RIBI in a London Cancer Centre. I then developed a template for a scoring model to explore how reporting of symptoms in the clinical setting might be improved. After investigating the use of cell-cycle markers as a marker of (chemo)-radiosensitivity, I then utilised these markers in colonic crypt cells to attempt to link the proliferative status after exposure to radiation to symptom presentation and severity. Methods and Results: A retrospective cohort study revealed 152 women treated for cervical and endometrial cancer with symptoms of RIBI, which were clustered into 3 groups using factor analysis. Exploratory and Confirmatory Factor Analysis was used to test a novel scoring model template. Immunostaining in 35 cervical tumour samples with the cell-cycle markers Mcm2, Geminin, and Ki67 did not find expression of these markers were linked to (chemo)-radiosensitivity and tumour response. These markers were used to assess proliferation in colo-rectal crypt cells and showed decreased expression in all layers suggesting a loss of proliferative capacity after radiation. Conclusions: Young patients with cervical cancer are more likely to develop significant symptoms of RIBI. Our simple scoring tool validated on a prospective cohort could provide invaluable data to improve management of women with bowel symptoms after radiation. Further work exploring proliferation in colonic crypt cells after radiation exposure could identify women at greater risk of radiation injury.

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