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Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma

机译:表观扩散系数(ADC)预测胰腺导管腺癌的治疗反应

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摘要

Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.
机译:胰腺导管腺癌(PDAC)分子亚型的最新进展支持这种最具有侵略性的疾病的治疗策略的个性化。随着在这种迅速恶化的疾病中出现各种新颖的治疗策略和新辅助方法,迫切需要用于快速评估治疗反应的可靠方法。为此,我们设计了一项临床前影像学指导的治疗试验,其中以靶向药物refametinib的MEK治疗携带内源性侵袭性PDAC的基因工程小鼠,从而在该模型系统中引起快速而深刻的肿瘤消退。多参数无创成像用于治疗反应监测。治疗开始后24小时,发现弥散加权磁共振成像得出的表观扩散系数(ADC)显着增加。组织病理学分析显示在此时间点细胞凋亡和基质重塑增加。我们的发现表明ADC参数可以作为PDAC治疗反应的早期预测指标。

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