Abstract B067: Novel Biological and Radiological Markers for Predicting Malignant Progression in IPMN: A Prospective Study

Abstract Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are the most frequently identified precursor lesions of pancreatic ductal adenocarcinoma (PDAC). However, only a minority of IPMNs progress to malignancy, making accurate risk stratification essential for effective cancer prevention. Current available guidelines lack precision, often leading to overtreatment of non-malignant lesions. The EMI-IPMN study (NCT06706700) aims to discover novel biological and radiological biomarkers capable of distinguishing malignant IPMNs. Special regard is placed on endocrine, metabolic, and inflammatory factors, which are known to play key roles in PDAC pathogenesis. Methods: Patients with a presumptive diagnosis of IPMN with surgical indication and high-quality MRI were prospectively enrolled. Peripheral Blood (PB) and Cyst Fluid (CF) were collected, and the lesions were classified as IPMN with High Grade Dysplasia (HGD), Low Grade Dysplasia (LGD), or Invasive Cancer (IC). Levels of cytokines, hormones and other factors were assessed in the fluids with Luminex assays and compared between the groups. Results: 205 patients were enrolled in the study. Among these patients, 130 had a diagnosis of IPMN, equally distributed between LGD, HGD and IC. The analysis revealed higher levels of several factors (IL-8, VEGF, GLP-1, Glucagon, GIP and C-peptide) in CF compared to PB. Specific cytokines, including MCP-1, IL-1b, TNFa and IL-8, were more represented in the CF of HGD/IC IPMN compared to LGD. In the PB the levels of IL-1b, IL8 and MDC were also higher in HGD/IC patients. These factors alone showed significant accuracy in identifying malignant IPMN, with an area under the ROC curve of 0,76, which improved when high-risk stigmata or worrisome features were considered (0,813 and 0,793 respectively). MRI studies also demonstrated higher pancreatic fat content, measured using mDixon Quant fat FRACTION sequences in MRI, in patients with HGD/IC compared to LGD (13,89% vs 8,38% respectively, p<0,05) and these findings correlate significantly with the levels of MCP-1 detected in the CF. Conclusions: The progression of IPMN towards PDAC is associated with a proinflammatory change in the tumor microenvironment, which manifests as both local (CF) and systemic (PB) alterations in various cytokines. These findings can be leveraged to detect the malignant transformation of IPMN early, with MRI serving as a potential proxy. These results also provide insights into the physiopathology of the transformation process. Citation Format: Benedetta Ferrara, Paolo Riccardo. Camisa, Diego Palumbo, Giulio Belfiori, Francesca Aleotti, Marco Schiavo Lena, Valeria Lanci, Laura Cerri, Francesca Di Salvo, Francesco De Cobelli, Claudio Doglioni, Massimo Falconi, Lorenzo Piemonti, Stefano Crippa. Novel Biological and Radiological Markers for Predicting Malignant Progression in IPMN: A Prospective Study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B067.