Abstract
Introduction: Systemic inflammatory markers (CRP, albumin) have been validated as prognostic factors in patients with resectable biliary tract cancer (BTC). The aim of this study was to determine specific immunologic prognostic markers by analyzing preoperative plasma samples from a large prospectively collected biobank. Methods: Expression of 92 proteins representing adaptive and innate immune responses was investigated in plasma from 102 patients undergoing resection for pathologically verified BTC at Karolinska University Hospital 2009-2017 (perihilar cholangiocarcinoma n=46, intrahepatic cholangiocarcinoma n=27, gallbladder cancer n=29), using a high-throughput multiplexed immunoassay. The primary outcome was overall survival. Association to survival was analyzed by Cox regression and discriminatory ability assessed with concordance index (c-index). Internal validation and calibration were performed and a nomogram employed to display a multivariable model. Results: Median follow-up time was 67 months. Median overall survival was 23 months. Three preoperative markers (univariable P≤0.001) were independently associated to overall survival: TRAIL (hazard ratio 0.29), TIE2 (hazard ratio 2.89) and CSF1 (hazard ratio 4.08). The bootstrap corrected c-index of a prognostic model with the three preoperative markers was 0.70. The corrected c-index of a model with postoperative pathology (T-stage, N-status, perineural and lymphovascular invasion, grade, resection margin) was 0.66. A preoperative prognostic nomogram was developed (Figure 1), also incorporating Glasgow prognostic score (CRP, albumin) and physical status (ASA class). Conclusion: A set of three preoperative immunological plasma markers was prognostic for overall survival in patients undergoing surgery for BTC and provided a prognostic model with good predictive ability, even compared to postoperative pathology.
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