TY - JOUR
T1 - Fecal, Duodenal and Tumor Microbiota Composition of Esophageal Carcinoma Patients, a Longitudinal Prospective Cohort
AU - van den Ende, Tom
AU - de Clercq, Nicolien C
AU - Davids, Mark
AU - Goedegebuure, Ruben
AU - Doeve, Benthe H
AU - Ebrahimi, Gati
AU - Buijsen, Jeroen
AU - Hoekstra, Ronald
AU - Mohammad, Nadia Haj
AU - Bijlsma, Maarten F
AU - Nieuwdorp, Max
AU - van Laarhoven, Hanneke W M
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press.
PY - 2024/11
Y1 - 2024/11
N2 - BACKGROUND: The microbiome has been associated with chemotherapy and immune checkpoint inhibitor efficacy. How this pertains to resectable esophageal carcinoma is unknown. Our aim was to identify microbial signatures in resectable esophageal carcinoma associated with response to neoadjuvant chemoradiotherapy with or without an immune checkpoint inhibitor. METHODS: From 2 prospectively collected esophageal carcinoma cohorts (n = 172 in total) treated with neoadjuvant chemoradiotherapy alone (n = 132) or a combination of neoadjuvant chemoradiotherapy and an immune checkpoint inhibitor (n = 40), fecal samples were available at baseline, during treatment, and presurgery. Additionally, in the immune checkpoint inhibitor-treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor, and duodenal DNA were extracted for 16S ribosomal RNA sequencing. Associations were investigated between microbiome composition pathological complete response and progression-free survival (PFS). RESULTS: There was a statistically significant shift in the microbiota profile of the fecal, tumor, and duodenal microbiota over time. In the total cohort, patients with a pathological complete response had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment (P = .036). Presurgery, lower alpha diversity (<4.12) was related to worse PFS (log-rank P = .025). Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS (log-rank P = .012). CONCLUSIONS: Lower intestinal alpha diversity was associated with worse response and survival of esophageal carcinoma patients. In tumor biopsies, Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for esophageal carcinoma patients.
AB - BACKGROUND: The microbiome has been associated with chemotherapy and immune checkpoint inhibitor efficacy. How this pertains to resectable esophageal carcinoma is unknown. Our aim was to identify microbial signatures in resectable esophageal carcinoma associated with response to neoadjuvant chemoradiotherapy with or without an immune checkpoint inhibitor. METHODS: From 2 prospectively collected esophageal carcinoma cohorts (n = 172 in total) treated with neoadjuvant chemoradiotherapy alone (n = 132) or a combination of neoadjuvant chemoradiotherapy and an immune checkpoint inhibitor (n = 40), fecal samples were available at baseline, during treatment, and presurgery. Additionally, in the immune checkpoint inhibitor-treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor, and duodenal DNA were extracted for 16S ribosomal RNA sequencing. Associations were investigated between microbiome composition pathological complete response and progression-free survival (PFS). RESULTS: There was a statistically significant shift in the microbiota profile of the fecal, tumor, and duodenal microbiota over time. In the total cohort, patients with a pathological complete response had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment (P = .036). Presurgery, lower alpha diversity (<4.12) was related to worse PFS (log-rank P = .025). Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS (log-rank P = .012). CONCLUSIONS: Lower intestinal alpha diversity was associated with worse response and survival of esophageal carcinoma patients. In tumor biopsies, Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for esophageal carcinoma patients.
UR - http://www.scopus.com/inward/record.url?scp=85208772035&partnerID=8YFLogxK
U2 - 10.1093/jnci/djae153
DO - 10.1093/jnci/djae153
M3 - Article
C2 - 38924513
SN - 0027-8874
VL - 116
SP - 1834
EP - 1844
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 11
ER -