72320 - External validation of plasma CSF1 as a preoperative prognostic marker in resectable intrahepatic cholangiocarcinoma – a bi-institutional study

Introduction The long-term prognosis after curative intent resection for intrahepatic cholangiocarcinoma (iCCA) remains poor. Preoperative risk assessment is difficult and neoadjuvant approaches have not yet been established. A previous single-centre study indicated two immune system-related proteins in plasma: colony stimulating factor 1 (CSF1) and TNF-related apoptosis-inducing ligand (TRAIL) as preoperative prognostic factors in iCCA. This study aimed to externally validate CSF1 and TRAIL as prognostic markers for patients with resectable iCCA, in collaboration between two Swedish regional referral centres. Method Preoperative plasma CSF1 and TRAIL concentrations were determined, from prospectively collected biobank samples using multiplex immunoanalysis (Proximity Extension Assay), for patients resected for iCCA at Karolinska (2010-2020) and Sahlgrenska (2019-2023) university hospitals. The primary outcome was overall survival (OS), analysed by Kaplan-Meier method and Cox regression. Result Sixty-one patients with resected iCCA were included (Karolinska n=45, Sahlgrenska n=16). CSF1 was significantly associated with OS with a hazard ratio (HR) of 1.03 (95% confidence interval [CI] 1.01-1.05). TRAIL showed no significant association with OS (HR 0.997 (95% CI 0.99-1.00). Elevated CSF1 concentrations were associated with poor survival, with a median OS of only 7 months for patients in the upper quartile, compared to an OS of 64 months for patients with CSF1 concentrations in the lower quartile (Figure 1, p<0.001). Discussion Plasma CSF1 was validated as a novel preoperative prognostic marker for patients with resectable iCCA, and could assist a preoperative risk stratification. The preoperative identification of high-risk patients could support individualized risk-benefit analyses and patient selection for prospective studies, including neoadjuvant strategies.