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000286750 1001_ $$aSchmäche, Tim$$b0
000286750 245__ $$aStratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold.
000286750 260__ $$aLondon$$bBiomed Central$$c2024
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000286750 520__ $$aThis study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx).Endoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into culture and PDOs expanded. PDOs' response towards the single substances of the FLOT regimen and the combination treatment were correlated to patients' pathological response using tumor regression grading. A classifier based on FLOT response of PDOs was established in an exploratory cohort (n = 13) and subsequently confirmed in an independent validation cohort (n = 13).EGC PDOs reflected patients' diverse responses to single chemotherapeutics and the combination regimen FLOT. In the exploratory cohort, PDOs response to single 5-FU and FLOT combination treatment correlated with the patients' pathological response (5-FU: Kendall's τ = 0.411, P = 0.001; FLOT: Kendall's τ = 0.694, P = 2.541e-08). For FLOT testing, a high diagnostic precision in receiver operating characteristic (ROC) analysis was reached with an AUCROC of 0.994 (CI 0.980 to 1.000). The discriminative ability of PDO-based FLOT testing allowed the definition of a threshold, which classified in an independent validation cohort FLOT responders from non-responders with high sensitivity (90%), specificity (100%) and accuracy (92%).In vitro drug testing of EGC PDOs has a high predictive accuracy in classifying patients' histological response to neoadjuvant FLOT treatment. Taking into account the high rate of successful PDO expansion from biopsies, the definition of a threshold that allows treatment stratification paves the way for an interventional trial exploring PDO-guided treatment of EGC patients.
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000286750 650_7 $$2Other$$aGastric cancer
000286750 650_7 $$2Other$$aPatient-derived organoids
000286750 650_7 $$2Other$$aPersonalized medicine
000286750 650_7 $$2Other$$aResponse prediction
000286750 7001_ $$aFohgrub, Juliane$$b1
000286750 7001_ $$aKlimova, Anna$$b2
000286750 7001_ $$0P:(DE-He78)2edb00bc9fd4fe7c858c2838ce1c0024$$aLaaber, Karin$$b3
000286750 7001_ $$aDrukewitz, Stephan$$b4
000286750 7001_ $$aMerboth, Felix$$b5
000286750 7001_ $$aHennig, Alexander$$b6
000286750 7001_ $$aSeidlitz, Therese$$b7
000286750 7001_ $$0P:(DE-He78)13dc15153ce40f775007112548f34d79$$aHerbst-Nowrouzi, Friederike$$b8$$udkfz
000286750 7001_ $$aBaenke, Franziska$$b9
000286750 7001_ $$aAda, Anne-Marlen$$b10
000286750 7001_ $$0P:(DE-He78)196be4790a587c09c4e13d8f91adcaa1$$aGroß, Thomas$$b11$$udkfz
000286750 7001_ $$aWenzel, Carina$$b12
000286750 7001_ $$0P:(DE-He78)7a10ea1b9b2872da9f375002c44ddfce$$aBall, Claudia$$b13$$udkfz
000286750 7001_ $$aPraetorius, Christian$$b14
000286750 7001_ $$aSchmidt, Thomas$$b15
000286750 7001_ $$aRingelband-Schilling, Barbara$$b16
000286750 7001_ $$aKoschny, Ronald$$b17
000286750 7001_ $$aStenzinger, Albrecht$$b18
000286750 7001_ $$aRoeder, Ingo$$b19
000286750 7001_ $$0P:(DE-He78)ed0321409c9cde20b380ae663dbcefd1$$aJäger, Dirk$$b20$$udkfz
000286750 7001_ $$aZeissig, Sebastian$$b21
000286750 7001_ $$aWelsch, Thilo$$b22
000286750 7001_ $$aAust, Daniela$$b23
000286750 7001_ $$0P:(DE-He78)157277fe62f07df1732f9d126a51d1b9$$aGlimm, Hanno$$b24$$udkfz
000286750 7001_ $$aFolprecht, Gunnar$$b25
000286750 7001_ $$aWeitz, Jürgen$$b26
000286750 7001_ $$0P:(DE-He78)f54d0426f2215c539d3a7ae1b400b57d$$aHaag, Georg Martin$$b27$$eLast author$$udkfz
000286750 7001_ $$aStange, Daniel E$$b28
000286750 773__ $$0PERI:(DE-600)2091373-4$$a10.1186/s12943-023-01919-3$$gVol. 23, no. 1, p. 10$$n1$$p10$$tMolecular cancer$$v23$$x1476-4598$$y2024
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