Serial cytokines as potential predictive/prognosis biomarkers in potentially resectable pancreatic adenocarcinoma

Mortality rate in pancreatic adenocarcinoma (PDAC) is similar to its incidence rate due to that almost 50% of the patients are diagnosed having metastasis and 1yOS for all stages barely over 20%. For this reason, new biomarkers (BKs) are urgently needed in order to improve patient outcomes in PDAC. In this sense, the main aim of this multicenter and prospective project is to find predictive and/or prognostic BKs based on many cytokines that are produced in cancer microenvironment and can nowadays be accurately analyzed. Patients diagnosed with potentially resectable PDAC with poor prognostic factors (CA 19.9 > 150 U/ml; suspected micrometastasis or low PS) and treated with neoadjuvant treatment are being prospectively included. Serial analyses (basal, with TC, with surgery and time of relapse/or after 1y of follow-up) of serum levels of 80 cytokines are being done. Since February 2018, with a median follow-up of 11,25 months (m) (4,67-38,28) 22 patients (pts) with median of age of 62,5 y-0, most of them men (63.6%) have been included, with radical surgery performed in 14 of them (2 pts with bypass). Seven operated pts received adjuvant treatment and 12 operated pts developed progression of disease. 18 pts have received nab-paclitaxel and gemcitabine as perioperative treatment and 4 received Folfirinox. Perineural and vascular invasion were confirmed after surgery in 45,5% and 27,3% of cases, respectively. Positive nodes were found in 40,9% of them, being the median of positive and resected nodes of 1 (0-14) and 26 respectively. Surgical margins were negative (R0) in 64,3% of cases (35,7% R1). Pathological response was described as partial in 13,6%, with no changes in 31,8% and progression in 13,6%. Globally, PFS and OS were 13,50 m (CI95%: 6,44-20,55) and 17.31 m (CI 95% 8,86-25,76), respectively. In K-M analysis, significant differences (p=0,002) were observed in cases in which radical surgery had been performed with a mean disease-free survival of 13,5 m (9,34-17,66) and 3.97 m (0-8,23) for unresectable patients. Regarding the cytokine array, we observed different PFS outcomes based on MCP3 levels (low: 16,32 m CI 95%: 5,02-27,63; high: 7,52 m CI95%: 6,23-8.81, p=0,023), oncostatin (high: 7,12 m CI95%: 3,09-11,15, low: not reached; p=0,007), eotaxin (low: 7,12 m CI 95%: 5,75-8,50; high: not reached, p=0,029). A cytokine score was created based on these results, which maintained significant differences in K-M for PFS (16,32 m CI95%: 5,07-27,57 vs 6,53 m CI95%: 2,75-10,32, p=0.003). Our cytokine score showed a significant role as an independent prognosis factor in multivariate analysis (HR: 0,196 CI95%: 0,042-0,918; p=0.039). In potentially resectable/borderline pancreatic adenocarcinoma, our basal cytokine score seems to be able to discriminate as an independent prognosis factor between those patients who will get significant benefit from neoadjuvant treatment from those who will not.