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@ARTICLE{Schmche:286750,
author = {T. Schmäche and J. Fohgrub and A. Klimova and K.
Laaber$^*$ and S. Drukewitz and F. Merboth and A. Hennig and
T. Seidlitz and F. Herbst-Nowrouzi$^*$ and F. Baenke and
A.-M. Ada and T. Groß$^*$ and C. Wenzel and C. Ball$^*$ and
C. Praetorius and T. Schmidt and B. Ringelband-Schilling and
R. Koschny and A. Stenzinger and I. Roeder and D. Jäger$^*$
and S. Zeissig and T. Welsch and D. Aust and H. Glimm$^*$
and G. Folprecht and J. Weitz and G. M. Haag$^*$ and D. E.
Stange},
title = {{S}tratifying esophago-gastric cancer treatment using a
patient-derived organoid-based threshold.},
journal = {Molecular cancer},
volume = {23},
number = {1},
issn = {1476-4598},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2024-00082},
pages = {10},
year = {2024},
note = {#LA:D120# / Correspondence},
abstract = {This study sought to determine the value of patient-derived
organoids (PDOs) from esophago-gastric adenocarcinoma (EGC)
for response prediction to neoadjuvant chemotherapy
(neoCTx).Endoscopic biopsies of patients with locally
advanced EGC (n = 120) were taken into culture and PDOs
expanded. PDOs' response towards the single substances of
the FLOT regimen and the combination treatment were
correlated to patients' pathological response using tumor
regression grading. A classifier based on FLOT response of
PDOs was established in an exploratory cohort (n = 13) and
subsequently confirmed in an independent validation cohort
(n = 13).EGC PDOs reflected patients' diverse responses to
single chemotherapeutics and the combination regimen FLOT.
In the exploratory cohort, PDOs response to single 5-FU and
FLOT combination treatment correlated with the patients'
pathological response (5-FU: Kendall's τ = 0.411, P =
0.001; FLOT: Kendall's τ = 0.694, P = 2.541e-08). For FLOT
testing, a high diagnostic precision in receiver operating
characteristic (ROC) analysis was reached with an AUCROC of
0.994 (CI 0.980 to 1.000). The discriminative ability of
PDO-based FLOT testing allowed the definition of a
threshold, which classified in an independent validation
cohort FLOT responders from non-responders with high
sensitivity $(90\%),$ specificity $(100\%)$ and accuracy
$(92\%).In$ vitro drug testing of EGC PDOs has a high
predictive accuracy in classifying patients' histological
response to neoadjuvant FLOT treatment. Taking into account
the high rate of successful PDO expansion from biopsies, the
definition of a threshold that allows treatment
stratification paves the way for an interventional trial
exploring PDO-guided treatment of EGC patients.},
subtyp = {Letter},
keywords = {Gastric cancer (Other) / Patient-derived organoids (Other)
/ Personalized medicine (Other) / Response prediction
(Other)},
cin = {B280 / DD01 / D120},
ddc = {570},
cid = {I:(DE-He78)B280-20160331 / I:(DE-He78)DD01-20160331 /
I:(DE-He78)D120-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38200602},
doi = {10.1186/s12943-023-01919-3},
url = {https://inrepo02.dkfz.de/record/286750},
}