Tumor Microenvironment: Insights from Multiparametric MRI in Pancreatic Ductal Adenocarcinoma.

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 Ktrans values 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 and ρ = -0.77, p = 0.009 for rΔve). In patients with PDAC, pre-treatment mean ADC and Ktrans values 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.