| Title: |
Predicting acute diarrhoea in rectal cancer chemoradiotherapy: Secondary analysis of the phase III ARISTOTLE trial |
| Authors: |
Zhang, Y.; Brand, D.; Shen, Z.; Simard, M.; Hindocha, S.; Chohan, O.; Lopes, A.; Begum, R.; West, N.; Appelt, A.; Gilbert, A.; Miles, E.; Maughan, T.; Sebag-Montefiore, D.; Hawkins, M.A.; Collins Fekete, C-A. |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, but acute diarrhoea remains a significant side effect, affecting the completion of chemoradiotherapy treatment. Purpose This study aimed to predict acute diarrhoea after neoadjuvant chemoradiotherapy for rectal cancer and further develop a strategic tool to individualise rectal cancer treatment. Materials and methods The ARISTOTLE trial is a phase III trial comparing capecitabine chemo-radiotherapy (CRT) versus capecitabine-irinotecan CRT as a pre-operative treatment for locally advanced rectal cancer. We included 589 trial patients across 73 institutions. The volume of the AI-segmented small bowel receiving at least 10 Gy (V10Gy) was used alongside the treatment arm, patient age, and performance status in a logistic regression model to predict a more than 2-grade increase in acute diarrhoea toxicity from baseline (ΔG ≥ 2). Finally, based on the prediction, we identified a sub-cohort of patients for whom a viable dose decrease would result in a reduction of toxicity, and conversely, we also identified individuals for whom adding irinotecan may not cause toxicity. Results The average mean receiver operating characteristic curve (AUROC) for predicting ΔG ≥ 2 is 0.71 [95 % CI 0.58–0.82] on the independent test dataset. Based on the prediction, we identified 71 patients (14 %) who could potentially benefit from irinotecan addition without a dose decrease to maintain ΔG < 2, and 77 patients (15 %) who could potentially benefit from irinotecan addition but need a dose decrease to maintain ΔG < 2. Conclusion The multi-institutional cohort of 73 centres strengthens the reliability of these findings, demonstrating the model’s potential as a strategic tool to individualise rectal cancer treatment while mitigating severe diarrhoea. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0167-8140 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/229241/3/1-s2.0-S0167814025045360-main.pdf; Zhang, Y., Brand, D., Shen, Z. et al. (13 more authors) (2025) Predicting acute diarrhoea in rectal cancer chemoradiotherapy: Secondary analysis of the phase III ARISTOTLE trial. Radiotherapy & Oncology, 210. 111032. ISSN: 0167-8140 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/229241/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.B5D1DD54 |
| Database: |
BASE |