131 - Gut Microbiota Predictive of Consolidation Immunotherapy Efficacy and Toxicity after Chemoradiotherapy in Lung Cancer
Presenter(s)
Y. Li1, L. Wu1,2, H. Ge3, M. Cui4, and N. Bi5; 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China, 3Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China, 4Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China, 5State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Purpose/Objective(s): The gut microbiota (GM) serves as a predictor for immune checkpoint inhibitors (ICIs) response in advanced lung cancer patients. However, its role in patients at locally advanced stages undergoing chemoradiotherapy (CRT) combined with consolidative ICIs remains poorly understood.
Materials/Methods: A total of 177 fecal samples were collected pre- and post-CRT. Utilizing 16S rRNA sequencing and metagenomics data from an internal cohort and published studies, the kinetics of microbiota were analyzed using Wilcoxon signed-rank test, while prognostic factors for progression-free survival (PFS) were identified through Cox regression modeling and machine learning algorithms.
Results: Traditional CRT unaltered the GM configuration. In the context of CRT with ICIs consolidation, patients with long-PFS showed higher alpha-diversity at baseline and followed by a reduction during treatment, contrasting with the stable diversity observed in the short-PFS group. The symbiotic microbiota Akkermansia muciniphila (Akk) enriched after CRT, with its increased abundance correlating with extended distant metastasis-free survival (DMFS) in patients receiving CRT with ICIs consolidation. Notably, the trend of Akk variation served as a predictive indicator for survival outcomes in patients undergoing CRT combined with ICIs. The GM also involved in the development of treatment related pneumonia and held promise as a predictive marker for severe pneumonia.
Conclusion: The effects of CRT with ICIs consolidation on GM appear more pronounced compared to CRT alone in locally advanced lung cancer patients. The dynamic information of Akk has the predictive potential for patient survival in this context.