Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, Dresden, 01307, Germany.
National Center for Tumor Diseases Dresden (NCT/UCC), a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
Mol Cancer. 2024 Jan 10;23(1):10. doi: 10.1186/s12943-023-01919-3.
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 AUC 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.
本研究旨在确定源自食管胃腺癌（EGC）的患者来源类器官（PDO）在预测新辅助化疗（neoCTx）反应中的价值。
对局部晚期 EGC 患者（n=120）进行内镜活检并进行培养和 PDO 扩增。使用肿瘤消退分级将 PDO 对 FLOT 方案的单一药物和联合治疗的反应与患者的病理反应相关联。在探索性队列（n=13）中建立基于 PDO 对 FLOT 反应的分类器，然后在独立验证队列（n=13）中进行验证。
EGC PDO 反映了患者对单一化疗药物和 FLOT 联合方案的不同反应。在探索性队列中，PDO 对单药 5-FU 和 FLOT 联合治疗的反应与患者的病理反应相关（5-FU：Kendall's τ=0.411，P=0.001；FLOT：Kendall's τ=0.694，P=2.541e-08）。FLOT 检测的诊断精度在接受者操作特征（ROC）分析中达到了很高的水平，AUC 为 0.994（CI 0.980 至 1.000）。基于 PDO 的 FLOT 检测的鉴别能力允许定义一个阈值，该阈值可以在独立验证队列中以高敏感性（90%）、特异性（100%）和准确性（92%）将 FLOT 应答者与非应答者区分开来。
EGC PDO 的体外药物测试在分类患者对新辅助 FLOT 治疗的组织学反应方面具有很高的预测准确性。考虑到从活检中成功扩增 PDO 的高比例，定义一个允许分层治疗的阈值为探索 PDO 指导 EGC 患者治疗的干预性试验铺平了道路。
