• Stephan B Dreyer, Mark Pinese, Nigel B Jamieson, Christopher J Scarlett, Emily K Colvin, Marina Pajic, Amber L Johns, Jeremy L Humphris, Jianmin Wu, Mark J Cowley, Angela Chou, Adnan M Nagrial, Lorraine Chantrill, Venessa T Chin, Marc D Jones, Kim Moran-Jones, Christopher Ross Carter, Euan J Dickson, Jaswinder S Samra, Neil D Merrett, Anthony J Gill, James G Kench, Fraser Duthie, David K Miller, Susanna Cooke, Daniela Aust, Thomas Knösel, Petra Rümmele, Robert Grützmann, Christian Pilarsky, Nam Q Nguyen, Elizabeth A Musgrove, Peter J Bailey, Colin J McKay, Andrew V Biankin, David K Chang, Australian Pancreatic Cancer Genome Initiative, and Glasgow Precision Oncology Laboratory.
• Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland, United Kingdom.
• Ann. Surg. 2020 Aug 1; 272 (2): 366-376.

ObjectiveWe aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.BackgroundAlthough we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.MethodIn 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.ResultsHigh expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.ConclusionsOf those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

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