Microbiome Dynamics During Chemoradiotherapy for Anal Cancer
Authors: Lin Daniel , El Alam Molly B. , Jaoude Joseph Abi , Kouzy Ramez , Phan Jae L. , Elnaggar Jacob H. , Resendiz Brianna , Medrano Andrea Y. Delgado , Lynn Erica , Nguyen Nicholas D. , Noticewala Sonal S. , Mathew Geena G. , Holliday Emma B. , Minsky Bruce D. , Das Prajnan , Morris Van K. , Eng Cathy , Mezzari Melissa P. , Petrosino Joseph F. , Ajami Nadim J. , Klopp Ann H. , Taniguchi Cullen M. , Colbert Lauren E. 
Published: September 2021

AbstractIMPORTANCEPatients 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.OBJECTIVETo longitudinally characterize the SCCA tumor microbiome and assess its association with treatment-related toxicities.DESIGNProspective cohort study.SETTINGSingle tertiary cancer center.PARTICIPANTSTwenty-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 MEASURESDiversity and taxonomic characterization of the SCCA microbiome throughout chemoradiotherapy using swab-based anorectal microbial specimen collection and 16S rRNA gene sequencing.RESULTSTwenty-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 RELEVANCEOur 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.Key PointsQUESTIONHow does the squamous cell anal tumor microbiome change during chemoradiotherapy, and how do these changes influence treatment-related toxicity?FINDINGSProspective longitudinal characterization of anal cancer patients revealed significant modulation of the local tumor microbiome in response to chemoradiotherapy including shifts in overall composition and differential enrichment of key taxa.Additionally, enrichment of specific taxa at baseline was associated with increased levels of treatment-related toxicities by the end of treatment.MEANINGThe anal tumor microbiome is significantly altered by chemoradiotherapy and could potentially serve as a biomarker for treatment-related toxicities.