DCE-MRI guided Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer

PROJECT SUMMARY / ABSTRACT Choosing the more effective therapy is imperative for borderline-resectable pancreatic cancer (BRPC). BRPC is a subcategory of pancreatic adenocarcinoma (PDAC) (about 20% of the entire PDAC cases). BRPC contacts peripancreatic arteries and/or veins but has the potential to be successfully resected after downstaging with

effective neoadjuvant therapy. Currently, there are two first-line therapeutic options for BRPC patients, nab- paclitaxel with gemcitabine and FOLFIRINOX. Overall response rates of these regimens are comparable (20- 30%), and there are no robust data favoring one over the other. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential as a non-invasive tool

for early evaluation of PDAC response to chemotherapy. PDAC is typically hypo-perfused due to significant tumor sclerosis creating elevated interstitial pressure and consequently compressing tumor-feeding vessels. However, an effective therapy induces acute necrosis, reducing interstitial pressure and increasing perfusion.

As DCE-MRI can measure tissue perfusion by monitoring the dynamic change of MRI contrast agents introduced intravenously, it can detect perfusion increase in responding PDAC before the morphological change of tumors. However, variability in quantitative DCE-MRI measurement remains a concern. We developed a perfusion phantom named P4 (Point-of-care Portable Perfusion Phantom) to reduce the

variability in quantitative DCE-MRI measurement. The reproducibility of quantitative DCE-MRI measurement (e.g., volume transfer constant: Ktrans) of various abdominal tissues across three MRI scanners significantly increased after P4-based error correction (Intraclass correlation coefficient: 0.39 vs. 0.98).

We demonstrated that quantitative DCE-MRI could be used to identify the early therapeutic response of PDAC after P4-based error correction. In our pilot study, DCE-MRI was applied for 20 PDAC patients before and 6-8 weeks after therapy initiation. The Ktrans of pancreatic tumors favorably responding to chemotherapy increased

84±26% (n=11) after P4-based error correction, while that of non-responding tumors did not (-7±11%) (n=9) (p