Abstract 4693: Impact of pelvic radiation on vaginal microbiome and pelvic health: Findings from the GEORGIA Trial (NCT04713618)

Abstract Radiation therapy (RT) is a common treatment for gynecological and lower gastrointestinal cancers with negative side effects on pelvic health and sexual function. These effects significantly impact patients’ quality of life, yet research on mitigating such toxicities remains limited. RT has been shown to alter the vaginal microbiome, enriching opportunistic pathogens, which may contribute to vaginal toxicity and treatment resistance. This study aims to assess how pelvic health, and the microbiome change over the course of and after treatment, and whether pre-treatment microbiome composition can predict post-treatment outcomes. Here we describe the results of the GEORGIA trial (NCT04713618) a longitudinal study of women undergoing pelvic radiation for anal, rectal, cervical, endometrial, vaginal, or vulvar cancer. We assessed the effect of RT on the metatranscriptome (metaT), evaluating microbial abundance, activity, and human gene transcription by sequencing total RNA with human ribosomal depletion to a depth of >50M reads per sample on an Illumina NextSeq 2500. Samples were collected at baseline and at 1, 3, 6-, 12-, 18-, and 24-months post-treatment. Longitudinal mixed-effects models were used the assess the relationship between clinical variables and microbes, with a random intercept by patient, using lme4 in R. Vaginal length changes pre/post-treatment were analyzed via paired t-tests, while vaginal diameter changes were assessed using the Wilcoxon rank-sum test. A total of 72 patients were recruited and of those 68 (94%) participants completed the sociodemographic questionnaire. The median age was 56.5 ranging from 28 to 90 years old. Most participants were white (90%), postmenopausal before treatment (62%), and married or partnered (65%). Vaginal swab RNAseq reads aligned to human and microbe reference genomes in approximately equal numbers. Deconvolving the human reads to immune cells showed increased neutrophils following RT (p = 0.05). We observed a significant change in vaginal diameter over the course of treatment (Wilcoxon rank sum, p = 0.04). Women with Candida-positive microbiomes experienced a significant reduction in vaginal diameter over time, compared to women with Candida-negative microbiomes (p = 0.03). The findings suggest a potential role for fungi, and particularly Candida, in treatment-associated vaginal changes and sexual health. These results imply a therapeutic target to improve patient outcomes via modulation of the vaginal microbiome. Citation Format: Yogita Mehra, Elizabeth LaPlante, Laura Flora, Caroline Dravillas, January Kim, Jessica Aduwo, Naa Korley, Alexandra Diaz, Eric Miller, Kenneth Pitter, Nyelia Williams, Rebecca Hoyd, Xiaokui Mo, Daniel Spakowicz, Laura Chambers, Elizabeth K. Arthur, Allison M. Quick. Impact of pelvic radiation on vaginal microbiome and pelvic health: Findings from the GEORGIA Trial (NCT04713618) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4693.