Background/Objectives:The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by an enriched stroma, hampering the effectiveness of therapy. This co-clinical study aimed to (1) provide insight into early post-treatment changes in the TME using multiparametric magnetic resonance imaging (mpMRI)-derived quantitative imaging biomarkers (QIBs) in a preclinical PDAC model treated with radiotherapy and correlate these QIBs with histology; (2) evaluate the feasibility of obtaining these QIBs in patients with PDAC using clinically approved mpMRI data acquisitions.Methods: Athymic mice (n= 12) at pre- and post-treatment as well as patients with PDAC (n = 11) at pre-treatment underwent mpMRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) data acquisition sequences. DW and DCE data were analyzed using monoexponential and extended Tofts models, respectively. DeepLIIF quantified the total percentage (%) of tumor cells in hematoxylin and eosin (H&E)-stained tissues from athymic mice. Spearman correlation and Wilcoxon signed rank tests were performed for statistical analysis.Results: In the preclinical PDAC model, mean pre- and post-treatment ADC and Ktransvalues differed significantly (p< 0.01), changing by 20.50% and 20.41%, respectively, and the median total tumor cells quantified by DeepLIIF was 24% (range: 15–53%). Post-treatment ADC values and relative change in ve(rΔve) showed a significant negative correlation with total tumor cells (ρ= −0.77,p< 0.014 for ADC andρ= −0.77,p= 0.009 for rΔve). In patients with PDAC, pre-treatment mean ADC and Ktransvalues were 1.76 × 10−3(mm2/s) and 0.24 (min−1), respectively.Conclusions: QIBs in both preclinical and clinical settings underscore their potential for future co-clinical research to evaluate emerging drug combinations targeting both tumor and stroma.
背景/目标：胰腺导管腺癌（PDAC）的肿瘤微环境（TME）以丰富的间质为特征，这阻碍了治疗的有效性。本项共临床研究旨在：（1）通过多参数磁共振成像（mpMRI）衍生的定量成像生物标志物（QIBs），在临床前PDAC放疗模型中探究TME的早期治疗后变化，并将这些QIBs与组织学相关联；（2）评估使用临床批准的mpMRI数据采集方案在PDAC患者中获取这些QIBs的可行性。
方法：在治疗前和治疗后对无胸腺小鼠（n=12）以及治疗前对PDAC患者（n=11）进行mpMRI检查，包括扩散加权（DW）和动态对比增强（DCE）数据采集序列。分别采用单指数模型和扩展Tofts模型分析DW和DCE数据。DeepLIIF量化了无胸腺小鼠苏木精-伊红（H&E）染色组织中肿瘤细胞的总百分比。采用Spearman相关分析和Wilcoxon符号秩检验进行统计分析。
结果：在临床前PDAC模型中，治疗前后的平均ADC值和Ktrans值存在显著差异（p<0.01），分别变化了20.50%和20.41%；经DeepLIIF量化的肿瘤细胞总数中位值为24%（范围：15–53%）。治疗后ADC值以及ve的相对变化（rΔve）与肿瘤细胞总数呈显著负相关（ADC：ρ=−0.77，p<0.014；rΔve：ρ=−0.77，p=0.009）。在PDAC患者中，治疗前的平均ADC值和Ktrans值分别为1.76×10−3（mm²/s）和0.24（每分钟）。
结论：临床前和临床环境中的QIBs强调了它们在未来共临床研究中的潜力，可用于评估针对肿瘤和间质的新型药物组合。
Tumor Microenvironment: Insights from Multiparametric MRI in Pancreatic Ductal Adenocarcinoma
肿瘤(癌症)患者之家