Prognostic host phenotypes based on body composition and systemic inflammation predict survival in patients with resected pancreatic and periampullary cancer

INTRODUCTION: Most present-day survival-models of patients with cancer do not account for tumor-host interactions. We hypothesized that host phenotypes based on systemic inflammation and body composition are prognostic of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We performed a post-hoc analysis of the nationwide PORSCH-trial, including all patients undergoing pancreatoduodenectomy for PDAC. Primary outcome was OS. Body composition analysis was performed using automatic segmentation (Mosamatic™) of preoperative abdominal computed tomography scans. Low muscle mass and myosteatosis were defined using log-rank stratification of sex-standardized Z-values of skeletal muscle index and radiation attenuation, respectively. Patients were clustered in eight host phenotypes based on combinations of adverse host factors: [1] low muscle mass, [2] myosteatosis, [3] systemic inflammation (C-reactive protein >6mg/L). Their association with OS was tested using multivariable-adjusted Cox-proportional hazard-analysis. Distinct combinations of adverse host factors were stratified into low-, intermediate-, and high-risk phenotypes according to k-means clustering based on log hazard-ratio's. RESULTS: 549 patients were included. The high-risk phenotype, characterized by the presence of all adverse host factors, showed lower median OS than intermediate ([1], [2], [1 +2], [1 +3], [2 +3]) and low-risk ([3]; none) phenotypes (13.0 months [95%CI 11.4-19.3] vs. 21.9 months [95%CI 19.3-24.7] vs. 35.2 months [95%CI 29.2-45.3], respectively; p < 0.001). In multivariable analysis, host phenotypes were associated with OS (adjusted [a]HR 1.39 [95%CI 1.08-1.80, p = 0.01; aHR 2.10 [95%CI 1.53-2.88], p < 0.01, for intermediate- and high-risk respectively), independent of tumor stage. DISCUSSION: Host phenotypes based on body composition and systemic inflammation predict OS independent of tumor stage in patients with resected PDAC, underscoring the importance of tumor-host interactions for clinical survival prediction.