1094 - The Longitudinal Oral Metatranscriptome Associated with Oropharyngeal Cancer Definitive Chemoradiation Toxicity
Presenter(s)
E. Gogineni1, K. Chakravarthy2, I. Manring3, M. Mestres-Villanueva4, D. L. Mitchell1, D. M. Blakaj5, M. Bonomi6, P. Bhateja6, S. Baliga1, J. C. Grecula1, D. J. Konieczkowski1, S. J. Ma7, S. Zhu8, S. Valentin9, Y. Mehra2, S. Jahanbakhshi2, J. Fischer2, S. J. Daniel4, D. Spakowicz9, and S. R. Jhawar4; 1Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 2The Ohio State University James Cancer Hospital, Columbus, OH, 3The Ohio State University Department of Radiation Oncology, Columbus, OH, United States, 4Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 5Department of Radiation Oncology, James Cancer Hospital, The Ohio State University, Columbus, OH, 6Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 7Ohio State University, Columbus, OH, 8University of Florida, Gainesville, FL, 9The Ohio State University Wexner Medical Center, Columbus, OH
Purpose/Objective(s):
Patients undergoing definitive chemoradiation for head and neck cancers experience high rates of toxicity. To mitigate these adverse effects, it is necessary to identify toxicity biomarkers and the optimal time to measure them. Recently, the microbiome of various sites (e.g., gut) has been associated with cancer treatment outcomes across several modalities (e.g., immunotherapy). In this prospective trial, we aimed to determine whether changes in the oral microbiome throughout chemoradiation would be linked to treatment-related toxicity. We hypothesized that patients who developed severe toxicities would exhibit a different oral microbiome compared to patients who did not experience toxicity during treatment.Materials/Methods:
Patients with oropharyngeal cancer received definitive chemoradiation (CRT) in 33-35 fractions on the OROMIC trial (OSU-20074). Oral swabs were collected from 34 patients at baseline, 4 weeks on treatment, 7 weeks on treatment, and 1-month follow-up using an OMR-110 kit containing a nucleic acid stabilizing solution. Samples were processed for total RNAseq, human ribo-depleted, and sequenced by Illumina Nextseq 2×150bp to a depth greater than 50 million reads/sample. Metatranscriptomes were aligned to a custom database using Kraken2. Throughout the study, we monitored and graded the development of dygeusia, dermatisis, xerostomia, dysphagia, and secretions. Using mixed-effects models, we compared differences in oral microbiome and high-grade (CTCAE grade 2-3) toxicity.Results:
The most common high-grade toxicity after 7 weeks of treatment was dermatitis (70.6%), followed by mucositis (64.7%), dysphagia (50%), dysgeusia (47.0%), and secretions (44.1%). We observed over 1900 microbial genera, including bacteria, fungi, and viruses. Bacteria were the most abundant, dominated by the phylum Proteobacteria (33.9%). The fraction of human transcripts significantly increased over time (p < 0.001), suggesting increased epithelial sloughing associated with treatment. The development of several high-grade toxicities (dermatitis, secretions, and dysgeusia) at 7 weeks was associated with an increased abundance of Sediminibacterium, and Nibribacter (p < 0.001). On the other hand, increases in the abundance of Ureaplasma, Lutibacter, and Kerstersia from baseline were protective (p < 0.001).Conclusion:
Over half of patients receiving definitive chemoradiation for oropharyngeal cancer experienced high-grade toxicities. We observed a relationship between the change in the oral metatrascriptome and the development of high-grade toxicity and protection from it. These findings will help find potential toxicity biomarkers and develop therapeutics to manage or ameliorate adverse effects from treatment.