PB0170 - Preoperative biomarker panel with fibrinogen and FVIII improves prognostic evaluation of pancreas cancer with neoadjuvant therapy

Background: Pancreatic ductal adenocarcinoma (PDAC) has rising incidence and 2-year mortality of around 80%. The prognosis has not improved during the past years. Simultaneously, PDAC is a highly thrombogenic cancer. We have previously shown that combination of CA 19-9 with fibrinogen (Fg) and FVIII improves preoperative diagnostic accuracy vs. the routine markers.

Aims: We analyzed the prognostic precision of this panel pre-operatively in neoadjuvant treated (NAT) and upfront surgically (US) treated PDAC patients.

Methods: The study was conducted under ethical and institutional permits and funded by Governmental grant. PDAC patients with available preoperative coagulation variables and operated (1/2010-6/2021) at our tertiary hospital were followed for at least two years or until death. Borderline resectable patients received NAT. Exclusion included inoperability, another malignancy within five years or preoperative anticoagulant therapy. CBC, CRP, clotting times, fibrinogen, FVIII, VWF, antithrombin, D-dimer, liver enzymes, amylase, CA 19-9, and CEA were assessed before surgery. Disease-specific and -free survival (DSS, DFS) was analyzed with the Kaplan Meier and Cox regression.

Results: Among 205 patients included, 76 received NAT. The median (IQR) follow-up was 2.3 years (1.2-4.1), ending with only 46 (22%) patients alive. Fibrinogen levels were higher in the US vs. patients operated after NAT (p <.001). Yet, Fg (>6.3 g/l) and FVIII (>267 IU/dl) associated with worse DSS (2.2 vs. 5.1 years) among the NAT (Fig 1), unlike the US patients. Other independent prognostic factors in NAT PDAC were CRP and CEA, perivascular invasion, and resection status. Patients with Fg/FVIII within references (n=13) had a 60% probability of 5-year survival.

Conclusion(s): Perivascular invasion was an adverse sign. Accordingly, preoperatively elevated levels of Fg and FVIII were associated with poor prognosis among NAT patients, especially when combined with CA 19-9 panel score. Further studies should investigate whether these patients would benefit from the panel-targeted anticoagulant treatments during NAT and before surgery.