ESTRO 2024 - Abstract Book

S5286 ESTRO 2024 1 University of Aberdeen, Rowett Institute, Aberdeen, United Kingdom. 2 University of Aberdeen, Institute of Medical Sciences, Aberdeen, United Kingdom. 3 Taipei Medical University Shuang-Ho Hospital, Department of General Medicine, New Taipei City, Taiwan Radiobiology - Normal tissue radiobiology

Purpose/Objective:

In the UK and other parts of the world, cases of pelvic malignancies are on the rise in the elderly. As many as 120,000 new cases of pelvic cancers (including anal, bladder, cervical, endometrial, colorectal and prostate cancer) are reported in the UK annually. Conventional treatments include surgery, radiotherapy and chemotherapy. While radiotherapy is well tolerated by the elderly, surgery is usually unsuitable for them due to age-related health problems such as atheroma, increased blood pressure, and heart and lung diseases. In palliative and curative settings, more than half of all cancer patients receive radiation-based therapy but this is associated with toxicities such as increased urinary and bowel frequency, rectal bleeding, tiredness and long-term bladder shrinkage and bowel fibrosis. Therefore, there is an urgent need to find radiosensitising agents which pose minimal toxicity to normal tissues for such patients. Growing evidence from research suggests that altering the gut microbiota by dietary fibre supplementation before/during radiotherapy can radiosensitise cancer cells and lessen the toxicity to normal tissues after radiation. The gut microbiota digests dietary fibre to produce short-chain fatty acids (SCFAs) including acetate, butyrate and propionate, which influence a range of health-promoting functions including protection against cancer and enhancement of cancer treatment. Soluble dietary fibres (e.g. pectin and inulin) are shown to have health benefits such as maintaining the intestinal barrier, improving physical bowel function and reducing glucose and cholesterol absorption. Apple pectin has also been shown to induce apoptosis in colorectal cancer cells. Psyllium on the other hand is an insoluble fibre that has been used to reduce the severity of radiation-induced diarrhoea. This study aimed to examine the effects of pectin and psyllium plus pectin in alleviating acute normal tissue toxicity post-irradiation.

Material/Methods:

Mice were fed diets containing different dietary fibres (0.2% cellulose, pectin, psyllium, psyllium plus pectin) for 2 weeks and irradiated at different doses (10 – 14 Gy) supine to the lower abdomen. Mice were killed at 3.75 days and small and large intestines were harvested. Colon length and caecal surface area were measured using Qupath image analysis software (version 0.4.4). Swiss rolls were made from the small intestine and colon, and formalin fixed for assessment of intestinal crypt regeneration. ANOVA was used to compare differences in effect between the different dietary fibres and p <0.05 was considered statistically significant.

Results:

Irradiation at 10 – 14 Gy showed no statistically significant difference in mouse colon length between the different dietary fibre groups. However, caecal surface area was observed to shrink with increasing doses of ionising radiation. Caecal surface area was significantly increased for mice fed on pectin (p=0.0317) and pectin plus psyllium (p=0.0009) as compared to those fed on 0.2% cellulose. In mice irradiated to 12 Gy, those fed psyllium, pectin and psyllium plus pectin had significantly (p=0.01) increased regenerating crypts at 3.75 days compared to mice fed on 0.2% cellulose. Similarly, after 14 Gy, increased regenerating crypts were found in the pectin (p=0.021) and psyllium (p=0.024) groups.

Conclusion: