Association of the anorectal microbiome and patient-reported gastrointestinal outcomes in patients with anal cancer.

Abstract

e15504 Background: Among patients with anal cancer undergoing chemoradiotherapy, the association between the microbiome and toxicity is not well documented. We sought to quantify the gastrointestinal-related patient-reported outcomes (PROs) and local microbiome profiles of patients with anal cancer receiving chemoradiotherapy in order to check for potential profiles that can help in predicting toxicity during treatment. Methods: We prospectively followed patients with non-metastatic squamous cell carcinoma of the anal canal who received definitive chemoradiotherapy. Anorectal swab samples were collected before treatment initiation and at 4 subsequent timepoints. Consequently, PROs were collected using the bowel subdomain of the Expanded Prostate Cancer Index Composite (EPIC). Samples were sequenced using 16S rRNA of the V4 region. Sequence reads were grouped by amplicon sequence variants (ASV’s) representative of unique bacterial species. We then used Linear discriminant analysis Effect Size (LEfSe) with an effect size of 4 to identify taxa at baseline that were differentially enriched in patients with high vs. low toxicity by end of treatment. We compared the EPIC scores with the relative abundance of species identified in the LEfSe using a paired Wilcoxon test. Results: The study included 22 patients (18 women and 4 men), whose median age was 59 years. Most patients were Stage III (59%) with negative HIV status (94%). The majority of patients (91%) received standard of care chemoradiotherapy. Overall toxicity was the highest at week 5 of treatment. At all individual time points, alpha diversity of the microbiome did not correlate with patient-reported GI function, additionally overall baseline diversity was not predictive of eventual GI outcomes. The LEfSe identified that patients with low patient reported toxicity at week 5 had higher of abundance of Selenomonas at baseline, while patients with higher toxicity had high abundance of baseline Actinobacteria, Peptoniphilus, Clostridiales , and Clostridia. When comparing the relative abundance of bacterial species among patients with high and low toxicities, patients with higher relative abundance of Clostridia and Actinobacteria had significantly higher toxicity (p = 0.03). Conclusions: Certain microbiome profiles at baseline are associated with anal cancer patients’ gastrointestinal-related PROs during chemoradiation. Our data provide novel avenues to study the potential uses of the local microbiome as a biomarker in predicting treatment toxicities in anal cancer.