Impact of radiologically identified embryological origin on recurrence patterns and survival in resectable pancreatic head adenocarcinoma.

4228 Background: The pancreatic head develops embryologically from the fusion of the dorsal pancreatic (Dp) and ventral pancreatic (Vp) buds, which differ in cellular composition. Although histopathology is considered the gold standard for distinguishing these structures, they can also be differentiated radiologically. The prognostic significance of the embryological origin of pancreatic head adenocarcinomas remains unknown. This study aimed to investigate the impact of tumor embryological location on survival outcomes in patients with resectable pancreatic head adenocarcinoma. Methods: Patients who underwent surgical resection for pancreatic head adenocarcinoma were retrospectively analyzed. Preoperative conmputed tomography images were used to determine the embryological tumor location. The boundary between Dp and Vp was defined as a line connecting the portal vein/superior mesenteric vein to the anterior margin of the intrapancreatic bile duct. Tumors located predominantly (≥80%) on one side of this boundary were classified accordingly, while tumors without ≥80% predominance in either region were classified as mixed. Patients were grouped as Vp, Dp, or mixed pancreatic (Mp) origin. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Results: A total of 164 patients were included. Tumor origin was classified as Vp in 74 patients (45.1%), Dp in 63 patients (38.4%), and Mp in 27 patients (16.5%). Mp tumors were associated with a significantly higher rate of grade 3 tumors (48.1% in Mp vs 21.6% in Vp and 23.8% in Dp, p = 0.005) and advanced T stage (T3–T4: 70.3% in Mp vs 32.4% in Vp and 47.6% in Dp, p = 0.009). Other baseline clinicopathological characteristics, and the rates of adjuvant chemotherapy and radiotherapy were similar among groups. Median PFS was 11.2 months (95% CI 10.5–11.9) in Mp, 13.0 months (95% CI 9.3–16.7) in Vp, and 9.8 months (95% CI 7.6–11.9) in Dp (p = 0.032). All recurrences in the Dp group were distant metastases, whereas Mp tumors recurred predominantly as distant metastases (85.7%) and Vp tumors showed a higher proportion of local recurrence (33.3%) (p < 0.001). Median OS was significantly longer in the Vp group (Mp: 16.7 months, 95% CI 8.9–27.4; Vp: 25.3 months, 95% CI 11.8–37.8; Dp: 16.7 months, 95% CI 13.2–20.3; p = 0.006). Conclusions: The embryological origin of pancreatic head adenocarcinoma is associated with distinct pathological features, survival outcomes, and recurrence sites. Vp-origin tumors demonstrate superior OS but higher local recurrence rates, whereas Dp-origin tumors are characterized by early distant metastasis. Preoperative CT-based identification of tumor origin serves as a non-invasive prognostic tool that may guide personalized adjuvant strategies, such as intensifying systemic therapy for Dp/Mp tumors or optimizing local control for Vp tumors.