TY  - JOUR
AU  - Schmäche, Tim
AU  - Fohgrub, Juliane
AU  - Klimova, Anna
AU  - Laaber, Karin
AU  - Drukewitz, Stephan
AU  - Merboth, Felix
AU  - Hennig, Alexander
AU  - Seidlitz, Therese
AU  - Herbst-Nowrouzi, Friederike
AU  - Baenke, Franziska
AU  - Ada, Anne-Marlen
AU  - Groß, Thomas
AU  - Wenzel, Carina
AU  - Ball, Claudia
AU  - Praetorius, Christian
AU  - Schmidt, Thomas
AU  - Ringelband-Schilling, Barbara
AU  - Koschny, Ronald
AU  - Stenzinger, Albrecht
AU  - Roeder, Ingo
AU  - Jäger, Dirk
AU  - Zeissig, Sebastian
AU  - Welsch, Thilo
AU  - Aust, Daniela
AU  - Glimm, Hanno
AU  - Folprecht, Gunnar
AU  - Weitz, Jürgen
AU  - Haag, Georg Martin
AU  - Stange, Daniel E
TI  - Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold.
JO  - Molecular cancer
VL  - 23
IS  - 1
SN  - 1476-4598
CY  - London
PB  - Biomed Central
M1  - DKFZ-2024-00082
SP  - 10
PY  - 2024
N1  - #LA:D120# / Correspondence
AB  - 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
KW  - Gastric cancer (Other)
KW  - Patient-derived organoids (Other)
KW  - Personalized medicine (Other)
KW  - Response prediction (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38200602
DO  - DOI:10.1186/s12943-023-01919-3
UR  - https://inrepo02.dkfz.de/record/286750
ER  -