Association of Gut Microbiome Characteristics With the Late Gastrointestinal Toxicities After Pelvic Receiving Radiation Treatment for Cervical, Vaginal, and Anal Cancers.

Abstract

PURPOSE/OBJECTIVE(S)\nRadiation therapy is curative for treating cervical, vaginal, and anal cancers, but can lead to gut toxicities that reduce quality of life in recovering patients. Previously, higher gut microbiome diversity was shown to be positively correlated with less severe acute gastrointestinal (GI) toxicities per patient-reported assessments of bowel function. The goal of this study was to explore effects of gut microbiome diversity and composition on late GI toxicities. We hypothesized that the occurrence of late GI toxicities in patients that receive abdominal radiation therapy correlates with gut microbiome diversity.\n\n\nMATERIALS/METHODS\nWe collected and analyzed rectal swabs from 66 patients with cervical, anal, and vaginal cancer receiving standard of care treatment. Samples from baseline and week 5 of treatment were sequenced using 16Sv4 ribosomal RNA (rRNA) gene sequencing. We also retrospectively evaluated the late (occurring after 3 months) radiation induced GI toxicities of patients who had completed their treatment 2 years prior using the RTOG/EORTC Late Radiation Morbidity Scoring Schema and the Common Terminology Criteria for Adverse Events (CTCAE) v.5. The gut microbial diversity of the patients was then characterized by indexes of richness, evenness and diversity. 59 patients were included in the analysis; exclusion criteria were lack of either follow-up or microbiome data and receiving additional radiation therapy or chemotherapy. Independent students t-tests were used to compare the alpha diversity metrics between patients who experienced late toxicities and those who did not. Beta diversity was evaluated using linear discriminant analysis effect size (LEfSe) to identify bacteria taxa that were differentially enriched in groups of patients with no toxicity against those with toxicity, and independent t-tests were used to compare the relative abundances of these taxa between patients with and without late toxicities.\n\n\nRESULTS\n37.3% of patients per RTOG/EORTC criteria and 42.4% per CTCAE criteria experienced late GI toxicities (RTOG >\u202f=\u202f1, CTCAE >\u202f=\u202f1). Overall, neither the alpha diversity at baseline nor at week 5 was significantly different in patients who experienced late toxicities compared with those who didn t. Of the 22 taxa identified in the LEFse analysis, Sutterella species were higher at baseline in patients who did not experience late GI toxicities (0.21% vs. 0.72%, respectively, P\u202f=\u202f0.01 for RTOG/EORTC criteria; 0.19% vs. 0.79%, respectively, P\u202f=\u202f0.004 per CTCAE criteria).\n\n\nCONCLUSION\nThe presence of Sutterella was significantly associated with late toxicity, consistent with prior observations of acute toxicity. Overall, is no strong association between gut microbiome diversity and the presence of late GI toxicities in patients who have received radiation therapy for cervical, vaginal, and anal cancers. The observation has implications in the ongoing search for gut microbiome-targeted treatments for mitigating side effects of radiation.\n\n\nAUTHOR DISCLOSURE\nE.J. Lynn: None. M.B. El Alam: None. T. Karpinets: None. D. Lin: None. R. Kouzy: None. K. Court: None. X. Wu: None. M.P. Mezzari: None. N. Ajami: None. T. Solley: None. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca. L. Ramondetta: None. A. Jhingran: American Board of Radiology. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. K. Schmeler: None. B.D. Minsky: None. E.J. Koay: Research Grant; PANCAN-AACR, MD Anderson Cancer Center, Philips, National Institutes of Health, General Electric, Elekta, Stand Up 2 Cancer, Project Purple. Royalty; Taylor and Francis LLC. Patent/License Fees/Copyright; Pending Patent. I help coordinate scientific and advocacy activities for this Foundation, focused on radiation oncology. P. Das: Honoraria; MD Anderson Cancer Center Madrid, National Cancer Institute/Leidos, ASTRO. Consultant; Adlai Nortye. C.M. Taniguchi: Research Grant; NIH, Reaumond Foundation, Mark Foundation. Consultant; Phebra Pty, Ltd, Xerient Pharmaceuticals. Advise on various radiation products; Accuray. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. L. Colbert: None.