Abstract Book

ESTRO 37

S583

Purpose or Objective The limited radiotherapy tolerance of the small-bowel causes toxicity for many patients receiving abdominal or pelvic radiotherapy. We conducted a systematic review and meta-analysis using published datasets of dose- volume parameters with toxicity outcomes for the small bowel to analyse and model the relationship with toxicity. Material and Methods SCOPUS, EMBASE & MEDLINE were searched using keywords and subject headings. 952 unique results were screened to identify 16 publications reporting small- bowel dose-volumes and toxicity. Where suitable data were available (mean values with parametric measures of error) fixed-effects inverse-variance meta-analysis was used to compare irradiated small-bowel dose-volumes for cohorts of patients with and without grade ≥3 toxicity. For all other data, non-parametric correlation between irradiated small-bowel dose-volume and incidence of grade ≥3 toxicity was examined. Results On fixed-effects meta-analysis of three studies (total 203 patients), each of the dose-volume measures V 5Gy –V 40Gy were significantly greater (p < 0. 00001) for patients who suffered Grade ≥3 toxicity compared to those who did not. The absolute difference is largest for the lowest dose-volume parameter and decreases with increasing dose, however the relative difference in volume actually increases with increasing dose, (table). When data from all studies were examined together, no significant correlations were found. However, when data from studies of rectal cancer radiotherapy were examined separately, the V 10Gy , V 30Gy , V 35Gy , and V 40Gy all correlated with incidence of toxicity, most strongly for the V 10Gy (Spearmans correlation coefficient 0.888, CI 0.489-0.980, p = 0.003), for which the figure shows the fit of a univariate logistic regression model. Table. Results of meta-analysis including absolute and relative differences in volume of small bowel irradiated to threshold dose VxGy, between patients with Grade 0-2 and those with Grade ≥3 Toxicity.

Ab induced villous apoptosis, which can be wiped out by CD4 and CD8 antibodies. Tumor bearing can also enhance CTLA-4 Ab induced villous apoptosis. But neither combination of CTLA-4 Ab with intestinal radiation nor combination of CTLA-4 Ab with tumor bearing can induce enteritis. Finally, combination of CTLA-4 Ab, intestinal radiation and tumor bearing induced enteritis. There were morphological changes and neutrophil and T lymphocytes infiltration in jejunum. Conclusion Combination of CTLA-4 Ab, intestinal radiation and tumor bearing established an autoimmune enteritis mouse model. PO-1038 Mesenchymal Stem Cell therapy reduce fibrosis induced by abdomino-pelvic radiotherapy A. CHAPEL 1 , B. Usununier 1 , B. Lhomme 1 , C. Linard 1 , V. Holler 1 , M. Benderitter 1 1 Institut de Radioprotection et de Sûreté Nucléaire, PSE- Santé, Fontenay-aux-Roses- Paris, France Purpose or Objective The abdomino-pelvic area contains the main organs at risk for cancer (prostate, colon-rectum, cervix…). Treatment protocols often include radiotherapy which, while effective for sterilization of the tumor, can cause severe late complications, such as fibrosis. During such treatment, colon and rectum are especially susceptible to side effects, due to their rapid self-renewal. There currently exists no reliable therapy against fibrosis. Seeing how Mesenchymal Stem Cell (MSC) has proven effective in treating radiation injuries, we aimed at investigating their ability to reduce radiation-induced fibrosis to the colon and rectum. Material and Methods In vivo , we evaluated the effects of MSC transplantation in rats. Following a single dose 29 Gy colorectal irradiation MSCs were injected intravenously at different time points to study the efficacy of cell therapy prior and after fibrosis onset. Results MSCs were able to reduce fibrosis in both these situations, mainly through the inhibition of inflammatory pathways and the reduction of myofibroblast activation. Key mediators of the effect of MSCs have been identified during this study. To further understand the mechanisms underlying these effects, we set up an in vitro model of myofibroblast activation. Intestinal fibroblasts and smooth muscle cells, the main pro-fibrotic cells in the colon, were irradiated to induce changes similar to those observed in vivo . When cocultured with MSCs, we observed a decrease in profibrotic proteins secretion by these cells. Mediators identified in vivo have been confirmed as key players in this process, mainly through the disruption of the TGF-β1 pathway. Conclusion These results suggest that MSC therapy represents a promising strategy in the treatment of severe enteritis, rectitis induced by radiotherapy of prostate, bladder, uterus cancers. PO-1039 Meta-analysis of toxicity and small-bowel radiotherapy dose-volume: “omnibus consequentia” D. Holyoake 1 , M. Partridge 1 , M. Hawkins 1 1 CRUK MRC Oxford Institute for Radiation Oncology, Department of Oncology- University of Oxford, Oxford, United Kingdom

Figure. Plot of toxicity rate and small-bowel V 10Gy [cm 3 ] for rectal cancer radiotherapy, with logistic regression model (dashed line) and 69% confidence interval (dotted lines). Studies are labelled with the number experiencing toxicity and the total number in the cohort.