Microbiome Dynamics During Chemoradiotherapy for Anal Cancer

IMPORTANCE: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome9s influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients9 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 patients9 microbial profiles. Further studies into these microbial characterizations and associations are needed to elucidate the tumor microbiome9s role in predicting treatment-related outcomes for SCCA patients.