Temporally evaluating the Anal Cancer Microbiome during Chemoradiation Daniel Lin, Ramez Kouzy, Molly El Alam, Joseph Abi Jaoude, Bruce Minksy, Emma Holliday, Ann Klopp, Prajnan Das, Cathy Eng, Van Morris, Lauren Colbert, and Cullen Taniguchi *The University of Texas MD Anderson Cancer Center, Houston, TX, United States Objective: Despite high rates of 5-year survival for localized HPV-driven anal squamous cell carcinoma (ASCC), approximately 20% of patients succumb to disease after chemoradiation therapy (CRT). Microbiota play a significant role in the pathogenesis and protection of cervical and oropharyngeal cancers, but its role in ASCC remains unknown. The goal of our ongoing clinical trial is to characterize the local microbiome of ASCC and its changes throughout radiation therapy. Methods: We are currently enrolling patients with localized HPV-related ASCC undergoing external beam radiation treatment with concurrent 5-FU and cisplatin. Serial anorectal microbiota samples were collected utilizing a non-invasive swab biopsy technique at baseline, week 1, 3, and 5 (end of treatment) during CRT and at 3 months post-CRT. Microbiome sequencing was performed using 16s rRNA sequencing. Shannon Diversity Index (SDI) was used to measure alpha diversity. PERMANOVA was used for multivariate comparisons. Linear regression was used to evaluate temporal changes. Linear Discriminant Effect Size (LEFSe) analysis was used to identify changes in relative abundance of specific taxa. Results: This analysis includes 22 patients. Diversity of the anorectal microbiome decreased throughout chemoradiation treatment with Week 5 samples exhibiting decreased diversity vs. baseline (SDI: P = 0.028). A subsequent increase in diversity was observed for 3 months follow-up (SDI: P = 0.033). Multivariate analysis demonstrated unique bacteria populations for baseline vs. end of treatment (P = 0.027). Linear regression revealed increased Corynebacteriales (R2 = 0.20, P = 0.0002) and decreased Clostridia (R2 = 0.12, P = 0.003) throughout CRT. LEFse analysis revealed an enrichment of Corynebacteriales and a depletion of Clostridia at end of treatment compared to both baseline and 3 months follow-up. Conclusion: Chemoradiation of the ASCC results in significant shifts in overall diversity, composition, and specific taxa throughout treatment. However, many of these changes appear to resolve 3 months post-CRT, with follow-up samples exhibiting microbial profiles similar to baseline. Further investigation into the effects of radiation therapy on the tumor microbiome may lead to unique approaches in improving outcomes for ASCC patients.
University of Texas MD Anderson Cancer Center
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