Abstract A024: DCE-MRI-based biophysical simulation to forecast NAT response in HER2+ breast cancer patients, with glucose characterization and orthogonal validation using FDG-PET and 64Cu studies
Authors: Whitman John , Adhikarla Vikram , Rockne Russell , Tumyan Lusine , Mortimer Joanne , Huang Wei , Ramos Dorys Lopez , Peterson Joseph R. , Cole John A. 
Published: February 2024

Abstract
Background Regions of high metabolic activity within a tumor can increase tumor perfusion. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) are imaging methods used in cancer diagnosis; the former identifies perfusion of the tumor microenvironment and the latter provides a coarse readout of glucose metabolic activity. Here, we perform a pilot analysis in a unique cohort of patients who underwent DCE-MRI, 18FDG-PET and 64Cu-DOTA-Traztuzumab. We characterize the performance of our perfusion model SimBioSys-Microvasculature (SBS-MV). We use this model in 3D simulations of individual HER2+ breast cancer patients to forecast response to neoadjuvant chemotherapy (NAT). Methods SBS-MV is a modified Tofts model for pharmacokinetic modeling of DCE-MRI data, utilizing a tissue segmentation model developed in-house to inform parameter fits and ensure that the derived parameters fall within acceptable values on a tissue-by-tissue level. We evaluated the stability of the SBS-MV model by analyzing a separate cohort of 10 patients who underwent ultrafast DCE-MRI. By undersampling the original high temporal resolution data, we mimicked possible variation in standard-of-care (SoC) DCE studies and accessed the variability of our fits with respect to different subsets. Next, we analyzed data from a different cohort of 18 patients, each of whom underwent a pre-NAT SoC DCE-MRI study, a mid-treatment FDG PET study, and a mid-treatment 64Cu-DOTA-Trastuzumab study during treatment. Tissue segmentation and SBS-MV fits were performed on the pre-NAT DCE-MRI. Tightly cropped boxes encompassing the tumor in the 3D SBS-MV volumes and the PET volumes were created. Using these identified regions, all summary statistics were calculated and cross-correlated between imaging modalities. Results SBS-MV was stable to SoC-mimicking temporally undersampled ultrafast DCE-MRI series, demonstrating relatively little variability in the output parameters (a voxel wise median deviation of approximately 0.005 min−1). Further, we demonstrate that SBS-MV parameters (Ktrans, ve) are correlated with FDG SUVSA and 64Cu SUVSA. The glucose concentrations used in the biophysical simulations, which are derived from SBS-MV fits, were correlated with FDG SUVSA, indicating that downstream applications of the SBS-MV models still carry this perfusion information. Finally, using SBS-MV, our biophysical simulations of HER2-targeted therapy accurately predict patient response. In this small cohort, our biophysical simulations performed well, yielding predictive accuracy of 0.83 (sensitivity=0.83, specificity=0.83). Conclusion Our MV model extracts biologically meaningful perfusion parameters from standard clinical DCE-MRI time series, providing the same benefits of a comprehensive kinetic analysis without impacting clinical workflow. This approach could be used in research and clinical settings, offering actionable information on what drives individual patient therapeutic response for a more personalized care.
Citation Format: John Whitman, Vikram Adhikarla, Russell Rockne, Lusine Tumyan, Joanne Mortimer, Wei Huang, Dorys Lopez Ramos, Joseph R. Peterson, John A. Cole. DCE-MRI-based biophysical simulation to forecast NAT response in HER2+ breast cancer patients, with glucose characterization and orthogonal validation using FDG-PET and 64Cu studies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A024.