Significant Intra-pancreatic Fat Deposition as an Independent Prognostic Factor in High-grade Pancreatic...

High-grade pancreatic neuroendocrine neoplasms (panNENs) are rare but aggressive tumors with poor clinical outcomes. Metabolic alterations are frequently observed in panNENs and may reflect their metabolic reprogramming. Significant intra-pancreatic fat deposition (IPFD), defined as excessive pancreatic fat accumulation, has been linked to various pancreatic diseases and identified as a prognostic factor in pancreatic cancer.

This retrospective multicenter study aimed to evaluate the prognostic value of metabolic alterations, particularly significant IPFD, in patients with high-grade panNENs.

Between 2013 and 2024, 87 patients with high-grade panNENs from three centers were included. Significant IPFD was assessed on unenhanced computed tomography images, with a pancreas-to-spleen attenuation ratio <0.70. Other metabolic data were retrospectively obtained from previous clinical assessments and medical records.

Among 87 patients, 24 (27.6%) showed significant IPFD. Patients with significant IPFD were associated with tumors located in the pancreatic head (75.0% vs 49.2%, P = 0.030) and a higher prevalence of metabolic dysfunction-associated steatotic liver disease (20.8% vs 3.2%, P = 0.023). After adjustment for tumor differentiation and clinical stage, significant IPFD independently predicted worse overall survival (hazard ratio [HR] 2.134; 95% confidence interval [CI] 1.159-3.929, P = 0.015) and disease-specific survival (HR 2.167; 95% CI 1.137-4.133, P = 0.019). In contrast, other metabolic alterations, including obesity and metabolic syndrome, were not independently associated with survival.

Significant IPFD is an independent adverse prognostic factor for overall and disease-specific survival in patients with high-grade panNENs, highlighting its potential role in risk stratification and clinical decision-making.