Predictors of acute and late diarrhea in the treatment of anal cancer with concurrent chemoradiotherapy

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Abstract
Background and purpose: Treatment-related diarrhea is a challenge for patients treated with chemo-radiotherapy (CRT) for anal cancer in a curative setting. This study aims to investigate dosimetric and clinical predictors of acute and late diarrhea for patients treated with CRT or radiotherapy (RT) alone for anal cancer. Additionally, to investigate different bowel contouring methods ability to predict diarrhea. Patient/material and methods: Patients treated with CRT or RT alone in the prospective, observational DACG-I Plan-A study (2015–2021) were included. Toxicity endpoints were acute grade ≥2 diarrhea, and late grade ≥1 diarrhea recorded at 1 year after treatment (Common Terminology Criteria of Adverse Events (CTCAE), v4.0). Bowel volumes were contoured on the planning computed tomography (CT) as bowel cavity, bowel bag, individual bowel loops, and terminal ileum. Dosimetric variables included V15Gy, V30Gy, and V45Gy for the different bowel volumes. Clinical variables included tumor size, N-stage, and chemotherapy regimen. Logistic regression was used to evaluate the association between variables and toxicity. Results: Of the 290 patients included in this study, 116 (40%) experienced acute grade ≥2 diarrhea, and 56 of 256 (22%) had late grade ≥1 diarrhea. Patients treated with 5-FU/Capecitabine had a threefold higher risk of acute diarrhea compared to those receiving weekly Cisplatin or RT alone (p < 0.001). A trend indicating an increased risk of acute grade ≥2 diarrhea for patients with larger bowel volumes receiving radiation was observed. This was most pronounced for bowel bag V30Gy (p = 0.09); however, results from the different bowel contouring methods were similar. No parameters were predictive of late diarrhea. Interpretation: No dosimetric or clinical predictors of late diarrhea were found and only a trend was found between higher dose to bowel and risk of acute diarrhea. Treatment with 5-FU/Capecitabine showed a notable association with acute diarrhea. No contouring method was superior in predicting diarrhea.

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