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@ARTICLE{Rhle:304511,
author = {A. Rühle$^*$ and M. Krausz and E. B. Monroy Ordonez$^*$
and J. Heyer and A. R. Thomsen$^*$ and H. Schäfer$^*$ and
A. Kafkaletos$^*$ and P. Bronsert and R. Kesselring$^*$ and
A. Al-Ahmad and N. Schlueter and J. Wüster and A. Knopf and
A.-L. Grosu$^*$ and M. Proietti and M. Henke$^*$ and C.
Berlin$^*$ and N. H. Nicolay$^*$},
title = {{O}ral {L}achnoanaerobaculum {L}evels and {S}urvival in
{P}atients {W}ith {H}ead and {N}eck {C}ancer.},
journal = {JAMA otolaryngology - head $\&$ neck surgery},
volume = {nn},
issn = {2168-6181},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DKFZ-2025-01899},
pages = {nn},
year = {2025},
note = {epub},
abstract = {The oral microbiome plays a critical role in cancer
treatment responses, yet its influence on outcomes in
patients with head and neck squamous cell carcinoma (HNSCC)
undergoing (chemo)radiotherapy remains poorly understood.
Identifying specific microbiome signatures associated with
treatment effectiveness could provide novel prognostic
biomarkers and therapeutic targets.To investigate the
association between salivary Lachnoanaerobaculum spp
abundance and treatment outcomes in patients with HNSCC
undergoing (chemo)radiotherapy and to explore potential
mechanisms.This prognostic study analyzed saliva samples
from patients with HNSCC who were enrolled in 2 independent
prospective biomarker studies (SALIVA and ZissTrans) and
underwent definitive (chemo)radiotherapy. Oral microbiome
composition was assessed using 16S rRNA gene sequencing.
Tumor-infiltrating lymphocytes (TILs) were evaluated via
immunohistochemistry in patients with available data.
Findings were further assessed using data from The Cancer
Microbiome Atlas and The Cancer Genome Atlas. Sample
collection occurred from 2008 to 2011 (SALIVA) and from 2017
to 2022 (ZissTrans), and the data for this study were
analyzed from July to December 2024.Definitive
(chemo)radiotherapy.The primary outcome was locoregional
recurrence-free survival (LRFS) and a secondary outcome was
overall survival (OS). Additional secondary analyses
evaluated the association between Lachnoanaerobaculum spp
levels and TIL levels, and the incidence of severe
radiation-induced oral mucositis.The analysis included 92
patients with HNSCC (mean [SD] age, 61.1 [7.9] years; 15
female $[16.3\%]$ 77 male $[83.7\%]$ individuals) and found
that higher Lachnoanaerobaculum spp abundance was associated
with substantially improved LRFS (median, 69 vs 11 months;
hazard ratio [HR], 0.50; $95\%$ CI, 0.29-0.86) and OS
(median, 75 vs 27 months; HR, 0.54; $95\%$ CI, 0.30-0.98).
This finding was confirmed by multivariable Cox regression
(LRFS: HR, 0.50; $95\%$ CI, 0.25-1.00; OS: HR, 0.37; $95\%$
CI, 0.16-0.85). TILs were evaluated in 76 patients
$(82.2\%)$ and showed that increased Lachnoanaerobaculum spp
levels were associated with higher CD4-positive and
CD8-positive TIL counts. Lachnoanaerobaculum spp abundance
showed no meaningful association with severe
radiation-induced oral mucositis. Data from The Cancer
Microbiome Atlas (n = 157) indicated that higher
intratumoral Lachnoanaerobaculum spp levels were associated
with improved OS (HR, 0.62; $95\%$ CI, 0.39-0.98).
Transcriptomic analyses in The Cancer Genome Atlas cohort
further supported an immune-stimulated tumor
microenvironment in Lachnoanaerobaculum-high tumors.This
prognostic study found that higher salivary
Lachnoanaerobaculum spp abundance was associated with
improved tumor control and survival in patients with HNSCC
undergoing (chemo)radiotherapy. These findings support
further investigation into microbiome-targeted interventions
to improve HNSCC treatment effectiveness.},
cin = {FR01},
ddc = {610},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40932704},
doi = {10.1001/jamaoto.2025.2816},
url = {https://inrepo02.dkfz.de/record/304511},
}