Abstract 1156: A molecular pre-operative prognostic nomogram for resectable pancreatic cancer.
Authors: Chang David K. , Pinese Mark , Scarlett Christopher J. , Pajic Marina , Colvin Emily K. , Johns Amber L. , Wu Jianmin , Cowley Mark J. , Humphris Jeremy L. , Chou Angela , Nguyen Nam Q. , Nagrial Adnan M. , Chantrill Lorraine , Chin Venessa T. , Musgrove Elizabeth A. , Altekruse Sean , Gill Anthony J. , Kench James G. , Biankin Andrew V. 
Published: August 2014

Purpose: Defining clinically and biologically relevant phenotypes to inform treatment decisions in other cancers have led to substantial improvements in overall outcomes. About 80% of patients with pancreatic cancer (PC) succumb to the disease despite curative resection, many of whom recur within 6 months of surgery. These early recurrences demonstrate that current staging is inadequate and that there is a clear need to better define prognostic phenotypes prior to significant intervention. This study aimed to evaluate the potential clinical utility of biologically relevant molecules as prognostic factors in resected PC to define strategies that may improve current preoperative staging accuracy and inform treatment decisions.

Method: We assessed the relationship of aberrant expression of two pro-metastatic calcium-binding proteins, S100A2 and S100A4 with disease-specific survival in four independent cohorts of patients (total n = 547) who underwent operative resection for PC. A preoperative nomogram using pre-operatively assessable variables including biomarkers was derived and was compared to traditional prognostic variables and the postoperative nomogram.

Results: High S100A2 and S100A4 expressions were an independent poor prognostic factor in both the training (n = 76; HR = 2.00, 95% CI = 1.15 - 3.49, P = 0.0216 and HR = 3.34, 95% CI = 1.69 - 6.62, P = 0.0005 respectively) and validation (n = 316; HR = 1.73, 95% CI = 1.20 - 2.48, P = 0.0030 and HR = 1.65, 95% CI = 1.23 - 2.22, P = 0.0009 respectively) cohorts. These results were further validated in a prospective cohort (ICGC-APGI, n = 100) and another retrospective population based cohort (NCI SEER, n = 55). Aberrant expression of S100A2/A4 protein again stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram using only variables that could be measured preoperatively (age, tumour size, tumour location and molecular biomarkers), predicted survival better than nomograms derived using clinico-pathological variables, which are only determinable after surgery. A proof-of-principle study demonstrated that biomarker expression can be reliably assessed in preoperative EUS-FNA cell block samples.

Conclusion: S100A4 and S100A2 are one of the very few biomarkers that have been independently validated in multiple patient cohorts. Their aberrant expression stratifies PC into distinct prognostic groups and potentially enables more accurate preoperative prognostication through a nomogram. Biomarker assessment potentially enables accurate preoperative prognostication, which is more accurate than current staging methods. The development and application of such nomograms has the potential to improve patient selection for surgery and assist clinicians in making “tie-breaker” decisions that would ultimately improve the overall survival and quality of life for patients with PC.

Citation Format: David K. Chang, Mark Pinese, Christopher J. Scarlett, Marina Pajic, Emily K. Colvin, Amber L. Johns, Jianmin Wu, Mark J. Cowley, Jeremy L. Humphris, Angela Chou, Nam Q. Nguyen, Adnan M. Nagrial, Lorraine Chantrill, Venessa T. Chin, Elizabeth A. Musgrove, Sean Altekruse, Anthony J. Gill, James G. Kench, Andrew V. Biankin. A molecular pre-operative prognostic nomogram for resectable pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1156. doi:10.1158/1538-7445.AM2013-1156