Microbiome Dynamics During Chemoradiation Therapy for Anal Cancer

Authors

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

Publication Date

8-1-2022

Journal

International Journal of Radiation Oncology, Biology, Physics

DOI

10.1016/j.ijrobp.2022.04.037

PMID

35513187

Abstract

Purpose: 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 and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA gene sequencing was used to perform diversity and taxonomic characterization of the SCCA microbiome. Wilcoxon signed-rank tests were used to compare microbial diversity and abundance over time. Wilcoxon rank-sum tests were used to compare microbial profiles of high and low toxicity groups.

Results: Twenty-two patients with SCCA were included in this study with a median age of 58.5 years (range, 39-77 years), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiation therapy except for decreases in the Observed Features (P = .03) index at week 5 relative to baseline. Tumor microbial compositions changed significantly by the end of treatment (P = .03). Differential enrichment of bacteria at specific time points occurred during treatment, including the enrichment of Clostridia at follow-up (vs week 5, q = 0.019) and Corynebacterium at week 5 (vs baseline, q = 0.015; vs follow-up, q = 0.022). Patients experiencing high toxicity at week 5 had higher relative counts of Clostridia, Actinobacteria, and Clostridiales at baseline (P = .03 for all).

Conclusions: The tumor microbiome changes during and after chemoradiation therapy, and patient-reported toxicity levels are associated with patients' microbial profiles. Further studies into these microbial characterizations and toxicity associations will elucidate the tumor microbiome's role in predicting treatment-related outcomes for patients with SCCA.

Keywords

Adult, Aged, Anus Neoplasms, Carcinoma, Squamous Cell, Chemoradiotherapy, Female, Humans, Male, Microbiota, Middle Aged, Prospective Studies, RNA, Ribosomal, 16S

Published Open-Access

yes

Recommended Citation

Lin, Daniel; El Alam, Molly B; Jaoude, Joseph Abi; et al., "Microbiome Dynamics During Chemoradiation Therapy for Anal Cancer" (2022). Faculty, Staff and Student Publications. 4306.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4306