Abstract 1564P
Background
To explore the dynamic change of gut microbiota and metabolites and its predictive role in progression-free survival (PFS) in esophageal cancer (EC) after concurrent chemoradiotherapy (CCRT).
Methods
In this prospective study, 94 newly diagnosed EC patients were recruited. A total of 282 fecal samples were collected at 3 time points (T0, before CCRT; T1, 2 weeks after the initiation of CCRT; and T2, the end of CCRT). Gut microbiota and its metabolites were analyzed by 16S rRNA sequencing and untargeted metabolomics, respectively. Microbe-metabolite correlation networks were compared between patients in the long-PFS group (PFS ≥18.0 months) and short-PFS group (PFS <18.0 months). A random forest classifier was constructed to identify microbial signature related to PFS. Clinical and microbial factors potentially predictive of PFS were assessed in the univariate and multivariate Cox regression analysis.
Results
At baseline, there was no significant difference in the distribution of microbial species or pathway abundance between the two groups. The abundance of Bacteroidota and Acidobacteria increased, while the abundance of Firmicutes decreased after CCRT. Shannon index (P = .016) and PD index (P = .007) were significantly higher in the long-PFS group than for those in the short-PFS group at T1. These distinct changes in gut microbiota were accompanied by functional alterations in tryptophan, fatty acid, and bile acid metabolism and nucleotide biosynthesis pathways during CCRT. Further metabolomic analyses revealed that the distributions of metabolites from these four essential metabolic pathways varied in the two groups at T1. The PFS-prediction microbial signature at T1 included members of the Ruminococcus, and various strains from within the Blautia and Prevotella. The machine learning classifier based on gut microbiota and metabolites yielded an area under the ROC curve of 0.93. Multivariate analysis indicated PD index (P = .027), the abundance of Blautia (P = .033) and deoxycholic acid (P = .025) at T1 were independent predictors of PFS.
Conclusions
Gut microbiota and metabolites composition at 2 weeks after the initiation of CCRT were associated with PFS in EC. Further research is needed to confirm these results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fujian Cancer Hospital.
Funding
National Clinical Key Specialty Construction Program (Grant No. 2021).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1508TiP - The 1920-EORTC-BIORADON study: Molecular characterization of non-small cell lung cancer (NSCLC) and indoor radon exposure in Europe
Presenter: Laura Mezquita
Session: Poster session 21
1509TiP - The 1825-EORTC, ALKALINE: Activity of lorlatinib based on ALK resistance mutations on blood in ALK positive NSCLC patients previously treated with second generation ALK inhibitor
Presenter: Laura Mezquita
Session: Poster session 21
1510TiP - Efficacy study of osimertinib in treatment-naïve patients with EGFR mutant non-small cell lung cancer (NSCLC) according to TP53 mutational status (TEMPLE-2/NCT05785208)
Presenter: Antonio Vitale
Session: Poster session 21
1515P - Maintenance rucaparib after first-line platinum-based chemotherapy in advanced esophagogastric (OG) adenocarcinoma: Interim results from the PLATFORM trial
Presenter: Anderley Gordon
Session: Poster session 21
1518P - Zanidatamab (zani) plus chemotherapy (chemo) and tislelizumab (tis) as first-line (1l) therapy for patients (pts) with advanced HER2-positive (+) gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a phase Ib/II study
Presenter: Keun-Wook Lee
Session: Poster session 21
1520P - Perioperative treatment in resectable gastric cancer with spartalizumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): The GASPAR phase II trial
Presenter: Melanie Dos Santos
Session: Poster session 21