Computed tomography detected responses in pancreatic cancer are slow and infrequent after chemoradiation [2], [3] and [4] and underestimate the effectiveness of neoadjuvant therapy in patients with resectable disease [5] and [6]. In our prior series of 74 patients with unresectable pancreatic cancer treated with gemcitabine and radiotherapy, 11 patients (15%) achieved a CT detected partial response by RECIST, and no one achieved a complete response [4]. Additionally, the median time to CT detected partial response was 4.5 months from the start of radiation

(range 1.6-19.1 months). This timing would not be useful for making clinical decisions. Histopathologically, pancreatic cancer is characterized by a prominent desmoplastic reaction [7]. This large amount of connective tissue would not be expected to regress after therapy and likely contributes to the frequent misinterpretation of scans. Diffusion-weighted MK-2206 clinical trial MRI (dMRI) has the potential to overcome buy ABT-199 the weaknesses of CT imaging in patients with pancreatic cancer. Diffusion-weighted imaging is a pulse sequence (utilizing Echo Planar imaging or EPI sequence) that can measure the mobility of water molecules within tissue at the cellular level [8]. The diffusion of water in

tissue can be expressed as the apparent diffusion coefficient (ADC) which reflects overall diffusivity, and is dependent on many factors, including water mobility in intra- and extracellular spaces,

the relative volume of these spaces, cellular membrane integrity, macromolecular components and permeability [9]. ADC values have been correlated with tumor cellularity in patients [10]. Low ADC values are observed in dense and fibrotic tumors due to increased tissue cellularity and reduced extracellular volume. Conversely, high ADC values have been described within necrotic regions of tumors [11] and [12]. By distinguishing between necrotic and viable tumor, dMRI has the potential to detect and measure cellular changes that occur in response Edoxaban to successful therapies, such as chemoradiation. These changes would be expected to be detectable prior to macroscopic changes in mass, size or morphology since removal of tumor macromolecular debris occurs relatively slowly. In fact, clinical studies have shown that dMRI can predict tumor response often several months prior to detectable radiographic changes [13], [14], [15], [16], [17] and [18]. Therefore, we decided to study the effectiveness of dMRI to predict response in patients with pancreatic cancer receiving neoadjuvant chemoradiation therapy. Patients with resectable pancreatic cancer planning to undergo neoadjuvant chemoradiation therapy were eligible for this study. Patients had to have no contraindications to MRI, adequate renal function, and no prior history of radiation therapy to the abdomen. All participating subjects signed informed consent.