Microbiome Dynamics During Chemoradiotherapy for Anal Cancer

Abstract

IMPORTANCE: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome s influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients outcomes. OBJECTIVE: To longitudinally characterize the SCCA tumor microbiome and assess its association with treatment-related toxicities. DESIGN: Prospective cohort study. SETTING: Single tertiary cancer center. PARTICIPANTS: Twenty-two patients with biopsy-confirmed non-metastatic SCCA receiving standard-of-care chemoradiotherapy as part of an Institutional Review Board-approved study from April 2017 to July 2019. MAIN OUTCOMES AND MEASURES: Diversity and taxonomic characterization of the SCCA microbiome throughout chemoradiotherapy using swab-based anorectal microbial specimen collection and 16S rRNA gene sequencing. RESULTS: Twenty-two SCCA patients were included in this study with a median (range) age of 58.5 (39-77), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiotherapy, except for decreases in the Chao1 (P=0.03) and Observed Features (P=0.03) indices at week 5 relative to baseline. Tumor microbial compositions measured using weighted UniFrac changed significantly by the end of treatment (P=0.03). Linear discriminant analysis effect sizes revealed differential enrichment of bacteria at specific time points, including the enrichment of Clostridia at both baseline and follow-up and the enrichment of Corynebacterium at week 5. Patients experiencing high toxicity at week 5 had higher relative abundances of Clostridia, Actinobacteria, and Clostridiales at baseline (P=0.03 for all). CONCLUSIONS AND RELEVANCE: Our study presents the first longitudinal characterization of the SCCA microbiome throughout chemoradiation. The tumor microbiome undergoes significant changes during and after chemoradiotherapy, and patient-reported toxicity levels are associated with patients microbial profiles. Further studies into these microbial characterizations and associations are needed to elucidate the tumor microbiome s role in predicting treatment-related outcomes for SCCA patients.