Heads or tails? In-depth analysis of pancreatic cancer outcome according to tumor location

Background: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second deadliest cancer in Europe by 2030.Given the underlying differences in embryogenesis, the objectives of this study were to describe the clinical and molecular features and outcomes of PDAC based on the primary tumor location [head (H) or body/tail (B/T)].Patients and methods: A retrospective single-center study included patients with a histologically confirmed PDAC and known tumor location from 2012 to 2024.The molecular panels included in-house panel on tumor tissue, FoundationMedicine (tumor tissue) or FoundationOne Liquid CDx (liquid biopsy) panels.HR and P value were computed via Cox regression between H versus B/T tumors.Results: A total of 1011 patients were included, among them 520 patients (51%) with H-tumor.Molecular alterations were available for 373 patients.Most common genes altered were KRAS (78%), TP53 (69%), CDKN2A (24%), and SMAD4 (12%), without significant differences between the two groups.Median overall survival (OS) from diagnosis was 20.6 months [95% confidence interval (CI) 19.2-22.6 months] in H tumors compared with 16.2 months in B/T tumors (95% CI 14.2-17.8months, P = 0.00057).Median OS from metastatic diagnosis was 14.4 months in H tumors (95% CI 13.4-16.7 months) versus 12.9 months in B/T tumors (95% CI 11.0-14.9months, P = 0.033).In multivariable analysis, operated patients [hazard ratio (HR) 0.36, P < 0.001], lung-only metastases (HR 0.55, P = 0.003) and low neutrophil/lymphocyte ratio (HR 0.56, P < 0.001) were associated with a longer OS while liver metastases (HR 1.25, P = 0.02) and B/T primary tumor site (HR 1.23, P = 0.03) worsened the prognosis.Conclusions: In a large retrospective cohort, H-PDAC was found to have a longer median OS than B/T-PDAC from initial and metastatic diagnosis.