Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold
Background and aims: This study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx).Methods: Endoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into cultu...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 January 2024
|
| In: |
Molecular cancer
Year: 2024, Jahrgang: 23, Pages: 1-8 |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/s12943-023-01919-3 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s12943-023-01919-3
|
| Verfasserangaben: | Tim Schmäche, Juliane Fohgrub, Anna Klimova, Karin Laaber, Stephan Drukewitz, Felix Merboth, Alexander Hennig, Therese Seidlitz, Friederike Herbst, Franziska Baenke, Anne-Marlen Ada, Thomas Groß, Carina Wenzel, Claudia R. Ball, Christian Praetorius, Thomas Schmidt, Barbara Ringelband-Schilling, Ronald Koschny, Albrecht Stenzinger, Ingo Roeder, Dirk Jaeger, Sebastian Zeissig, Thilo Welsch, Daniela Aust, Hanno Glimm, Gunnar Folprecht, Jürgen Weitz, Georg M. Haag and Daniel E. Stange |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1888249765 | ||
| 003 | DE-627 | ||
| 005 | 20240703174748.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240510s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12943-023-01919-3 |2 doi | |
| 035 | |a (DE-627)1888249765 | ||
| 035 | |a (DE-599)KXP1888249765 | ||
| 035 | |a (OCoLC)1443676025 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Schmäche, Tim |d 1993- |e VerfasserIn |0 (DE-588)1241285047 |0 (DE-627)1770841334 |4 aut | |
| 245 | 1 | 0 | |a Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold |c Tim Schmäche, Juliane Fohgrub, Anna Klimova, Karin Laaber, Stephan Drukewitz, Felix Merboth, Alexander Hennig, Therese Seidlitz, Friederike Herbst, Franziska Baenke, Anne-Marlen Ada, Thomas Groß, Carina Wenzel, Claudia R. Ball, Christian Praetorius, Thomas Schmidt, Barbara Ringelband-Schilling, Ronald Koschny, Albrecht Stenzinger, Ingo Roeder, Dirk Jaeger, Sebastian Zeissig, Thilo Welsch, Daniela Aust, Hanno Glimm, Gunnar Folprecht, Jürgen Weitz, Georg M. Haag and Daniel E. Stange |
| 264 | 1 | |c 10 January 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 10. Januar 2024 | ||
| 500 | |a Gesehen am 10.05.2024 | ||
| 520 | |a Background and aims: This study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx).Methods: 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). Results: 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%). Conclusion: 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. | ||
| 650 | 4 | |a Gastric cancer | |
| 650 | 4 | |a Patient-derived organoids | |
| 650 | 4 | |a Personalized medicine | |
| 650 | 4 | |a Response prediction | |
| 700 | 1 | |a Fohgrub, Juliane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Klimova, Anna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Laaber, Karin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Drukewitz, Stephan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Merboth, Felix |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hennig, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Seidlitz, Therese |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herbst, Friederike |e VerfasserIn |0 (DE-588)1022072900 |0 (DE-627)715858246 |0 (DE-576)364281324 |4 aut | |
| 700 | 1 | |a Baenke, Franziska |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ada, Anne-Marlen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Groß, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wenzel, Carina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ball, Claudia R. |e VerfasserIn |0 (DE-588)133777294 |0 (DE-627)691804028 |0 (DE-576)300093799 |4 aut | |
| 700 | 1 | |a Praetorius, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmidt, Thomas |d 1980- |e VerfasserIn |0 (DE-588)132383152 |0 (DE-627)521950023 |0 (DE-576)260799149 |4 aut | |
| 700 | 1 | |a Ringelband-Schilling, Barbara |e VerfasserIn |4 aut | |
| 700 | 1 | |a Koschny, Ronald |d 1974- |e VerfasserIn |0 (DE-588)124377483 |0 (DE-627)70661836X |0 (DE-576)185833950 |4 aut | |
| 700 | 1 | |a Stenzinger, Albrecht |e VerfasserIn |0 (DE-588)139606106 |0 (DE-627)703395238 |0 (DE-576)312432755 |4 aut | |
| 700 | 1 | |a Roeder, Ingo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jäger, Dirk |d 1964- |e VerfasserIn |0 (DE-588)1032507535 |0 (DE-627)738505323 |0 (DE-576)380074125 |4 aut | |
| 700 | 1 | |a Zeißig, Sebastian |d 1979- |e VerfasserIn |0 (DE-588)130526169 |0 (DE-627)503040541 |0 (DE-576)298248840 |4 aut | |
| 700 | 1 | |a Welsch, Thilo |d 1977- |e VerfasserIn |0 (DE-588)129031313 |0 (DE-627)387883924 |0 (DE-576)187840148 |4 aut | |
| 700 | 1 | |a Aust, Daniela E. |e VerfasserIn |0 (DE-588)1043852360 |0 (DE-627)771001665 |0 (DE-576)174280815 |4 aut | |
| 700 | 1 | |a Glimm, Hanno |d 1967- |e VerfasserIn |0 (DE-588)113880677 |0 (DE-627)51985120X |0 (DE-576)289777879 |4 aut | |
| 700 | 1 | |a Folprecht, Gunnar |e VerfasserIn |0 (DE-588)1150889195 |0 (DE-627)101115174X |0 (DE-576)497322080 |4 aut | |
| 700 | 1 | |a Weitz, Jürgen |e VerfasserIn |0 (DE-588)1022345974 |0 (DE-627)716954451 |0 (DE-576)171632176 |4 aut | |
| 700 | 1 | |a Haag, Georg Martin |d 1979- |e VerfasserIn |0 (DE-588)133390934 |0 (DE-627)544043863 |0 (DE-576)29981548X |4 aut | |
| 700 | 1 | |a Stange, Daniel Eduard |d 1980- |e VerfasserIn |0 (DE-588)133390446 |0 (DE-627)691400105 |0 (DE-576)276050142 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cancer |d London : Biomed Central, 2002 |g 23(2024), Artikel-ID 10, Seite 1-8 |h Online-Ressource |w (DE-627)355987619 |w (DE-600)2091373-4 |w (DE-576)107015234 |x 1476-4598 |7 nnas |a Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold |
| 773 | 1 | 8 | |g volume:23 |g year:2024 |g elocationid:10 |g pages:1-8 |g extent:8 |a Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold |
| 856 | 4 | 0 | |u https://doi.org/10.1186/s12943-023-01919-3 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240510 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 133390934 |a Haag, Georg Martin |m 133390934:Haag, Georg Martin |d 910000 |d 910100 |d 50000 |e 910000PH133390934 |e 910100PH133390934 |e 50000PH133390934 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 28 | ||
| 998 | |g 113880677 |a Glimm, Hanno |m 113880677:Glimm, Hanno |d 50000 |e 50000PG113880677 |k 0/50000/ |p 25 | ||
| 998 | |g 1032507535 |a Jäger, Dirk |m 1032507535:Jäger, Dirk |d 50000 |e 50000PJ1032507535 |k 0/50000/ |p 21 | ||
| 998 | |g 139606106 |a Stenzinger, Albrecht |m 139606106:Stenzinger, Albrecht |d 910000 |d 912000 |e 910000PS139606106 |e 912000PS139606106 |k 0/910000/ |k 1/910000/912000/ |p 19 | ||
| 998 | |g 124377483 |a Koschny, Ronald |m 124377483:Koschny, Ronald |d 910000 |d 910100 |d 50000 |e 910000PK124377483 |e 910100PK124377483 |e 50000PK124377483 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 18 | ||
| 998 | |g 132383152 |a Schmidt, Thomas |m 132383152:Schmidt, Thomas |d 50000 |e 50000PS132383152 |k 0/50000/ |p 16 | ||
| 998 | |g 1022072900 |a Herbst, Friederike |m 1022072900:Herbst, Friederike |d 50000 |e 50000PH1022072900 |k 0/50000/ |p 9 | ||
| 999 | |a KXP-PPN1888249765 |e 4521994911 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"person":[{"display":"Schmäche, Tim","family":"Schmäche","role":"aut","given":"Tim"},{"family":"Fohgrub","display":"Fohgrub, Juliane","given":"Juliane","role":"aut"},{"given":"Anna","role":"aut","family":"Klimova","display":"Klimova, Anna"},{"role":"aut","given":"Karin","display":"Laaber, Karin","family":"Laaber"},{"display":"Drukewitz, Stephan","family":"Drukewitz","given":"Stephan","role":"aut"},{"given":"Felix","role":"aut","family":"Merboth","display":"Merboth, Felix"},{"role":"aut","given":"Alexander","family":"Hennig","display":"Hennig, Alexander"},{"role":"aut","given":"Therese","display":"Seidlitz, Therese","family":"Seidlitz"},{"given":"Friederike","role":"aut","family":"Herbst","display":"Herbst, Friederike"},{"given":"Franziska","role":"aut","family":"Baenke","display":"Baenke, Franziska"},{"given":"Anne-Marlen","role":"aut","display":"Ada, Anne-Marlen","family":"Ada"},{"family":"Groß","display":"Groß, Thomas","given":"Thomas","role":"aut"},{"role":"aut","given":"Carina","family":"Wenzel","display":"Wenzel, Carina"},{"display":"Ball, Claudia R.","family":"Ball","role":"aut","given":"Claudia R."},{"family":"Praetorius","display":"Praetorius, Christian","given":"Christian","role":"aut"},{"given":"Thomas","role":"aut","display":"Schmidt, Thomas","family":"Schmidt"},{"role":"aut","given":"Barbara","family":"Ringelband-Schilling","display":"Ringelband-Schilling, Barbara"},{"display":"Koschny, Ronald","family":"Koschny","role":"aut","given":"Ronald"},{"given":"Albrecht","role":"aut","family":"Stenzinger","display":"Stenzinger, Albrecht"},{"given":"Ingo","role":"aut","display":"Roeder, Ingo","family":"Roeder"},{"given":"Dirk","role":"aut","family":"Jäger","display":"Jäger, Dirk"},{"role":"aut","given":"Sebastian","family":"Zeißig","display":"Zeißig, Sebastian"},{"display":"Welsch, Thilo","family":"Welsch","given":"Thilo","role":"aut"},{"family":"Aust","display":"Aust, Daniela E.","role":"aut","given":"Daniela E."},{"family":"Glimm","display":"Glimm, Hanno","given":"Hanno","role":"aut"},{"display":"Folprecht, Gunnar","family":"Folprecht","given":"Gunnar","role":"aut"},{"role":"aut","given":"Jürgen","family":"Weitz","display":"Weitz, Jürgen"},{"family":"Haag","display":"Haag, Georg Martin","role":"aut","given":"Georg Martin"},{"family":"Stange","display":"Stange, Daniel Eduard","role":"aut","given":"Daniel Eduard"}],"name":{"displayForm":["Tim Schmäche, Juliane Fohgrub, Anna Klimova, Karin Laaber, Stephan Drukewitz, Felix Merboth, Alexander Hennig, Therese Seidlitz, Friederike Herbst, Franziska Baenke, Anne-Marlen Ada, Thomas Groß, Carina Wenzel, Claudia R. Ball, Christian Praetorius, Thomas Schmidt, Barbara Ringelband-Schilling, Ronald Koschny, Albrecht Stenzinger, Ingo Roeder, Dirk Jaeger, Sebastian Zeissig, Thilo Welsch, Daniela Aust, Hanno Glimm, Gunnar Folprecht, Jürgen Weitz, Georg M. Haag and Daniel E. Stange"]},"physDesc":[{"noteIll":"Illustrationen","extent":"8 S."}],"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"disp":"Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based thresholdMolecular cancer","pubHistory":["1.2002 -"],"note":["Gesehen am 25.06.20"],"origin":[{"publisherPlace":"London","publisher":"Biomed Central","dateIssuedKey":"2002","dateIssuedDisp":"2002-"}],"title":[{"title":"Molecular cancer","title_sort":"Molecular cancer"}],"id":{"issn":["1476-4598"],"zdb":["2091373-4"],"eki":["355987619"]},"recId":"355987619","physDesc":[{"extent":"Online-Ressource"}],"part":{"extent":"8","text":"23(2024), Artikel-ID 10, Seite 1-8","volume":"23","year":"2024","pages":"1-8"},"language":["eng"]}],"recId":"1888249765","id":{"doi":["10.1186/s12943-023-01919-3"],"eki":["1888249765"]},"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"10 January 2024"}],"note":["Online veröffentlicht: 10. Januar 2024","Gesehen am 10.05.2024"],"title":[{"title_sort":"Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold","title":"Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold"}],"type":{"media":"Online-Ressource","bibl":"article-journal"}} | ||
| SRT | |a SCHMAECHETSTRATIFYIN1020 | ||