H. Trembath1, J. Kearney1, H. Kim1, M. Meyers1, J. Yeh1 1University Of North Carolina At Chapel Hill, Department Of Surgery, Chapel Hill, NC, USA
Introduction: Pancreatic adenocarcinoma (PDAC) is an extremely lethal disease with dismal long term survival. The relationship between diabetes mellitus (DM) and PDAC is multifaceted and better understanding it is a stated NIH research priority. DM is a known PDAC risk factor; there is a subset of PDAC patients with new onset DM (NOD), who are diagnosed with PDAC <2 years after DM diagnosis that is currently under investigation regarding the pathophysiology, demographics, outcomes, as well as a potential group to screen.
There are two molecular subtypes of PDAC, basal and classical, that are prognostic and predictive of chemotherapy response. While subtyping assays have been developed, they are not yet utilized for majority of PDAC patients. We set out to evaluate if presence of NOD correlates with molecular subtype and could be used as a subtype proxy to help guide prognosis and treatment decisions.
Methods: This is a single institution, cohort study using retrospective review of hospital data and RNA sequencing data. To be included in the study, patients had to have PDAC on pathology specimen review, RNA sequencing data from resected specimen for molecular subtyping, and have undergone resection from 2009-2022. Demographic and clinical factors were examined using bivariate and multivariate analysis.
Results: We identified 139 patients that met inclusion criteria: 84 patients with no history of DM, 31 patients with longstanding DM (>2 years), 16 with NOD, and 8 patients with a missing date of DM diagnosis and were thus excluded from the analysis. There were 120 patients with classical subtype and 11 with basal subtype. The demographics between groups were overall similar, however BMI was higher in the group of longstanding DM compared to no DM (M=29.1 SD=5.4, M=25.8, SD=4.8), but not statistically different from NOD. After controlling for age, sex, race, and preoperative weight, NOD was not a significant predictor of PDAC subtype (OR 0.62, 95% CI 0.06, 6.1). Increasing age was associated with slightly decreased odds of having basal subtype (OR 0.91, 95% CI 0.85, 0.98, p value 0.02).
Conclusion: As continued interest in the NOD PDAC patient group mounts, we sought to see if NOD could be used in subtype prediction and hence, aid in prognosis and treatment choices. We are the first, to our knowledge, to show that NOD and PDAC subtype are not associated and NOD cannot be used to predict PDAC subtype at this time. Additionally, we found that sex, race, and preoperative weight are poor predictors of subtype. However, there could be different demographic or clinical factors that may be identified in the future to aid in subtype predication. Further investigation into underlying pathophysiology of the NOD group is still needed.
